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First in Human Phase1/2a Clinical Trial of Anti-PAUF Monoclonal Antibody PBP1510 in Patients With Pancreatic Cancer

Primary Purpose

Pancreatic Cancer

Status
Recruiting
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
PBP1510 (400mg/16mL)
Gemcitabine (1000 mg/m^2)
Sponsored by
Prestige Biopharma Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients enrolling into Part 1 (Phase 1), or Part 2 (Phase 2a) must meet all of the following inclusion criteria:

  1. Adults ≥ 18 years of age (or the legal age of majority in the country of recruitment) at the time consent is obtained.
  2. Patient should understand, voluntarily sign, and date the written consent form prior to any protocol-specific procedures.
  3. Performance Status score less than or equal to 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
  4. Have histological or cytological evidence of a diagnosis of pancreatic cancer that is advanced and/or metastatic.
  5. Have a life expectancy of ≥ 3 months.
  6. No other malignancy present that would interfere with the current intervention.
  7. Prior radiation therapy for treatment of cancer is allowed to < 25% of the bone marrow, and patients must have recovered from the acute toxic effects of their treatment prior to study enrolment. Prior radiotherapy must be completed at least 4 weeks before the first dose of study treatment.
  8. At least one measurable lesion as per RECIST v1.1
  9. Adequate baseline organ function defined as:

    ANC ≥ 1.5 × 10^9 /L; Haemoglobin ≥ 9 g/dL; Platelets ≥ 100 × 10^9 /L; Total bilirubin ≤ 2 × ULN (≤ 3 x ULN for patients with biliary stenting and patients with Gilbert's syndrome); AST and ALT < 3 x ULN (≤ 5 x ULN for patients with hepatic metastases); Serum creatinine OR creatinine clearance (as determined by the Cockcroft Gault formula) OR eGFR based on MDRD ≤ 1.5 x ULN OR ≥ 50 mL/min OR ≥ 50 mL/min/1.73 m^2; LVEF ≥ 50% by ECHO or MUGA; QTc ≤ 470 ms

  10. Female patients of nonchildbearing potential must meet at least 1 of the following criteria: have undergone a documented hysterectomy, and/or bilateral oophorectomy; have medically confirmed ovarian failure or achieved postmenopausal status. A postmenopausal state is defined as cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a follicle stimulating hormone (FSH) level confirming the postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. Female patients of childbearing potential must have a negative serum pregnancy test within 28 days prior to and negative urine pregnancy test just prior to the first dose of PBP1510 and agree to use effective contraception, in accordance with the recommendations of the Clinical Trials Facilitation and Coordination Group (CTFG) from study entry and until for at least 6 months after the last dose of PBP1510.
  11. For women of childbearing potential and men with partners of childbearing potential, agreement (by patient and/or partner) to use two effective forms of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) from study entry and until for at least 6 months after the last dose of PBP1510.

    Investigator or his/her representative should discuss acceptable pregnancy prevention method(s) with the patients. Highly effective methods of birth control include those that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, levonorgestrel-releasing intrauterine system, intra-uterine devices (IUDs), and true sexual abstinence.

  12. Patients must be willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.

    Patients enrolling into Part 1 (Phase 1) of the study must also meet the following inclusion criteria:

  13. Monotherapy and combination cohorts: advanced/metastatic pancreatic cancer patients whose tumours have progressed after at least one prior line of standard chemotherapy.

    Patients enrolling into Part 2 (Phase 2a) of the study must also meet the following inclusion criteria:

  14. Advanced/metastatic pancreatic cancer patients whose tumours have progressed after one prior line of standard chemotherapy.

Exclusion Criteria:

Patients enrolling into Part 1 (Phase 1), or Part 2 (Phase 2a) will be excluded if any of the following criteria apply:

  1. Patients who have known brain metastases will be excluded from the study. However, a patient may be included in the study, if has been previously treated for brain metastasis, the disease is well controlled for at least 3 months, and the patient is off steroids.
  2. Patients who have undergone a major surgery within 4 weeks prior to the start of PBP1510 administration, other than endoscopic/radiation procedures, bypass surgery (i.e., gastrojejunostomy), laparoscopy, port placement or a diagnostic surgery (i.e., surgery done to obtain a diagnostic biopsy, without removal of an organ), as long as the patient has recovered from these minor surgical procedures.
  3. Patients who have active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, e.g., an active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii (P. carinii), or other microorganisms that is under treatment with myelotoxic drugs.
  4. Patient has a known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
  5. Patient has known history of or currently active hepatitis B (e.g., hepatitis B antigen [HBsAg] reactive), hepatitis C (e.g., HCV RNA [qualitative] is detected) or syphilis [Venereal Disease Research Laboratory (VDRL) to detect antibodies in blood]).
  6. Patient has impaired cardiac function and uncontrolled cardiac diseases/hypertension that are deemed clinically significant by the Investigator and which could compromise the patient's safety or the study data integrity.
  7. Patient has serious psychiatric disorders, which could compromise the patient's safety or the study data integrity.
  8. Any other malignancy from which the patient has been disease-free for less than 5 years, except for adequately treated and cured basal or squamous cell skin cancer.
  9. Patients who are enrolled in any other therapeutic clinical trial.
  10. Patients currently receiving radiation therapy or those having received radiation within 4 weeks prior to study entry.
  11. Patients having received investigational anti-cancer drug within 28 days (or 5 half-lives, whichever is longer) preceding the first dose of PBP1510 or chemotherapy within the last 4 weeks prior to the first dose of PBP1510.
  12. Patients with known allergy or hypersensitivity to components of the PBP1510 formulation including the excipients and history of hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
  13. Patients who are pregnant, or breast feeding.
  14. Patients who are unwilling or unable to comply with study procedures.
  15. Patients who are not eligible to participate in this study, as judged by Investigators.
  16. A history of allergic reactions attributed to gemcitabine or compounds of similar chemical composition to gemcitabine.

Note: Patients with previous exposure to gemcitabine should not be excluded from the study.

Sites / Locations

  • Hospital Universitario La PazRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1M

Cohort 1C

Cohort 2M

Cohort 2C

Cohort 3M

Cohort 3C

Cohort 4M

Cohort 4C

Cohort 5M

Cohort 5C

Arm Description

1 mg/kg of PBP1510 as monotherapy will be administered

1 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered

3 mg/kg of PBP1510 as monotherapy will be administered

3 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered

6 mg/kg of PBP1510 as monotherapy will be administered

6 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered

10 mg/kg of PBP1510 as monotherapy will be administered

10 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered

15 mg/kg of PBP1510 as monotherapy will be administered

15 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered

Outcomes

Primary Outcome Measures

PART 1 (PHASE 1): To evaluate safety and tolerability of PBP1510
As assessed by evaluation of adverse events and serious adverse events (AE & SAE). AEs will be coded using MedDRA and grouped by system organ class and preferred term. An AE which is fatal or life threatening will be considered as SAE.
PART 1 (PHASE 1): Dose limiting toxicity (DLT) evaluation
DLTs will be assessed by the Investigator using the NCI-CTCAE V5.0.
PART 2 (PHASE 2a): To establish safety of PBP1510 in combination with gemcitabine
As assessed by evaluation of AEs and SAEs. AEs will be coded using MedDRA and grouped by system organ class and preferred term. An AE which is fatal or life threatening will be considered as SAE.
PART 2 (PHASE 2a): To assess the efficacy of PBP1510 in combination with gemcitabine
As assessed by objective response rate (ORR; rate of patients with complete response [CR] or partial response [PR]) evaluated by Response Evaluation Criteria in Solid Tumours version v1.1 (RECIST v1.1).

Secondary Outcome Measures

PART 1 (PHASE 1): Determine the recommended Phase 2a dose (R2PD) of PBP1510
The RP2D will be selected based on the analysis of the PK, safety, and efficacy data.
PART 1 (PHASE 1): Peak concentration (Cmax) of PBP1510 (µg/ml)
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
PART 1 (PHASE 1): Time to reach Cmax (Tmax) of PBP1510 (hr)
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
PART 1 (PHASE 1): Terminal elimination half-life (t1/2) of PBP1510 (hr)
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
PART 1 (PHASE 1): Area under the concentration-time curve (AUC) of PBP1510 (hr*µg /ml)
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
PART 1 (PHASE 1): Mean residence time (MRT) of PBP1510 (hr)
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
PART 1 (PHASE 1): Volume of distribution at steady state (Vss) of PBP1510 (mL/kg)
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
PART 1 (PHASE 1): Volume of the central compartment (Vc) of PBP1510 (mL/kg)
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
PART 1 (PHASE 1): Clearance (CL) of PBP1510 (mL/kg/hr)
• administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
PART 1 (PHASE 1): Peak concentration (Cmax) of gemcitabine (µg/ml)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
PART 1 (PHASE 1): Time to reach Cmax (Tmax) of gemcitabine (hr)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
PART 1 (PHASE 1): Terminal elimination half-life (t1/2) of gemcitabine (hr)
• administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
PART 1 (PHASE 1): Area under the concentration-time curve (AUC) of gemcitabine (hr*µg /ml)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
PART 1 (PHASE 1): Mean residence time (MRT) of gemcitabine (hr)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
PART 1 (PHASE 1): Clearance (CL) of gemcitabine (mL/kg/hr)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
PART 1 (PHASE 1): Presence of anti-drug antibody (ADA) and neutralizing antibodies (NAb) against PBP1510 administered as monotherapy, and in combination with gemcitabine.
following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Trough concentration (Ctrough) of PBP1510 (µg/ml)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Peak concentration (Cmax) of PBP1510 (µg/ml)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Time to reach Cmax (Tmax) of PBP1510 (hr)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Terminal elimination half-life (t1/2) of PBP1510 (hr)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Area under the concentration-time curve (AUC) of PBP1510 (hr*µg /ml)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Mean residence time (MRT) of PBP1510 (hr)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Volume of distribution at steady state (Vss) of PBP1510 (mL/kg)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Volume of the central compartment (Vc) of PBP1510 (mL/kg)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Clearance (CL) of PBP1510 (mL/kg/hr)
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Trough concentration (Ctrough) of Gemcitabine (µg/ml)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Peak concentration (Cmax) of Gemcitabine (µg/ml)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Time to reach Cmax (Tmax) of Gemcitabine (hr)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Terminal elimination half-life (t1/2) of Gemcitabine (hr)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Area under the concentration-time curve (AUC) of Gemcitabine (hr*µg /ml)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Mean residence time (MRT) of Gemcitabine (hr)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Clearance (CL) of Gemcitabine (mL/kg/hr)
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Progression-free survival (PFS) after treatment with PBP1510 administered in combination with gemcitabine
in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Overall Survival (OS) after treatment with PBP1510 administered in combination with gemcitabine
in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Duration of Response (DoR) after treatment with PBP1510 administered in combination with gemcitabine
in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
PART 2 (PHASE 2a): Presence of ADA and NAb against PBP1510 administered in combination with gemcitabine.
following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.

Full Information

First Posted
August 27, 2021
Last Updated
September 14, 2023
Sponsor
Prestige Biopharma Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05141149
Brief Title
First in Human Phase1/2a Clinical Trial of Anti-PAUF Monoclonal Antibody PBP1510 in Patients With Pancreatic Cancer
Official Title
A First in Human, Phase 1/2a, Multicentre, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of PBP1510 in Patients With Advanced/Metastatic Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 5, 2023 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prestige Biopharma Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The first in human clinical study is planned as an open-label, dose-escalation, and dose-expansion, multicentre, two-part, Phase 1/2a study of PBP1510 administered to patients with advanced/metastatic pancreatic cancer. The study will be conducted in two parts, Part 1 as a PBP1510 single agent dose-escalation, and PBP1510 dose-escalation in combination with gemcitabine, and Part 2 as PBP1510 dose-expansion at the RP2D in combination with gemcitabine.
Detailed Description
The first in human clinical study is planned as an open-label, multicentre, two-part, Phase 1/2a study to assess the safety, pharmacokinetics, and efficacy of PBP1510 in patients with advanced/metastatic pancreatic cancer. Part 1 (Phase 1) is a dose-escalation phase, wherein 2 cycles of PBP1510 will be administered, as monotherapy (monotherapy cohorts) or in combination with gemcitabine (combination cohorts) in advanced/metastatic pancreatic cancer patients whose tumours have progressed on at least one previous line of chemotherapy for locally advanced/metastatic disease. The RP2D will be selected based on the analysis of the PK, safety, and efficacy data. Part 2 (Phase 2a) will be an open-label study and patients will be administered the RP2D of PBP1510 derived from Part 1, for 4 cycles in combination with gemcitabine for advanced/metastatic pancreatic cancer patients whose tumour has progressed on one previous line of chemotherapy for locally advanced/metastatic disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1M
Arm Type
Experimental
Arm Description
1 mg/kg of PBP1510 as monotherapy will be administered
Arm Title
Cohort 1C
Arm Type
Experimental
Arm Description
1 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered
Arm Title
Cohort 2M
Arm Type
Experimental
Arm Description
3 mg/kg of PBP1510 as monotherapy will be administered
Arm Title
Cohort 2C
Arm Type
Experimental
Arm Description
3 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered
Arm Title
Cohort 3M
Arm Type
Experimental
Arm Description
6 mg/kg of PBP1510 as monotherapy will be administered
Arm Title
Cohort 3C
Arm Type
Experimental
Arm Description
6 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered
Arm Title
Cohort 4M
Arm Type
Experimental
Arm Description
10 mg/kg of PBP1510 as monotherapy will be administered
Arm Title
Cohort 4C
Arm Type
Experimental
Arm Description
10 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered
Arm Title
Cohort 5M
Arm Type
Experimental
Arm Description
15 mg/kg of PBP1510 as monotherapy will be administered
Arm Title
Cohort 5C
Arm Type
Experimental
Arm Description
15 mg/kg of PBP1510 and 1000 mg/m^2 of gemcitabine as combination therapy will be administered
Intervention Type
Drug
Intervention Name(s)
PBP1510 (400mg/16mL)
Intervention Description
Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Gemcitabine (1000 mg/m^2)
Intervention Description
Humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets and neutralizes PAUF, administered as a 90-minute intravenous infusion in combination with 1000 mg/m2 gemcitabine administered as a 30-minute intravenous infusion.
Primary Outcome Measure Information:
Title
PART 1 (PHASE 1): To evaluate safety and tolerability of PBP1510
Description
As assessed by evaluation of adverse events and serious adverse events (AE & SAE). AEs will be coded using MedDRA and grouped by system organ class and preferred term. An AE which is fatal or life threatening will be considered as SAE.
Time Frame
Baseline to follow up (Day 72)
Title
PART 1 (PHASE 1): Dose limiting toxicity (DLT) evaluation
Description
DLTs will be assessed by the Investigator using the NCI-CTCAE V5.0.
Time Frame
During first treatment cycle (each cycle is 28 days)
Title
PART 2 (PHASE 2a): To establish safety of PBP1510 in combination with gemcitabine
Description
As assessed by evaluation of AEs and SAEs. AEs will be coded using MedDRA and grouped by system organ class and preferred term. An AE which is fatal or life threatening will be considered as SAE.
Time Frame
Baseline to follow up (Day 120)
Title
PART 2 (PHASE 2a): To assess the efficacy of PBP1510 in combination with gemcitabine
Description
As assessed by objective response rate (ORR; rate of patients with complete response [CR] or partial response [PR]) evaluated by Response Evaluation Criteria in Solid Tumours version v1.1 (RECIST v1.1).
Time Frame
Baseline to end of treatment (Day 113)
Secondary Outcome Measure Information:
Title
PART 1 (PHASE 1): Determine the recommended Phase 2a dose (R2PD) of PBP1510
Description
The RP2D will be selected based on the analysis of the PK, safety, and efficacy data.
Time Frame
After follow up (Day 72)
Title
PART 1 (PHASE 1): Peak concentration (Cmax) of PBP1510 (µg/ml)
Description
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 1 (PHASE 1): Time to reach Cmax (Tmax) of PBP1510 (hr)
Description
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 1 (PHASE 1): Terminal elimination half-life (t1/2) of PBP1510 (hr)
Description
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 1 (PHASE 1): Area under the concentration-time curve (AUC) of PBP1510 (hr*µg /ml)
Description
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 1 (PHASE 1): Mean residence time (MRT) of PBP1510 (hr)
Description
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 1 (PHASE 1): Volume of distribution at steady state (Vss) of PBP1510 (mL/kg)
Description
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 1 (PHASE 1): Volume of the central compartment (Vc) of PBP1510 (mL/kg)
Description
administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 1 (PHASE 1): Clearance (CL) of PBP1510 (mL/kg/hr)
Description
• administered as monotherapy, and in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 1 (PHASE 1): Peak concentration (Cmax) of gemcitabine (µg/ml)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15. Each cycle is 28 days.
Title
PART 1 (PHASE 1): Time to reach Cmax (Tmax) of gemcitabine (hr)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15. Each cycle is 28 days.
Title
PART 1 (PHASE 1): Terminal elimination half-life (t1/2) of gemcitabine (hr)
Description
• administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15. Each cycle is 28 days.
Title
PART 1 (PHASE 1): Area under the concentration-time curve (AUC) of gemcitabine (hr*µg /ml)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15. Each cycle is 28 days.
Title
PART 1 (PHASE 1): Mean residence time (MRT) of gemcitabine (hr)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15. Each cycle is 28 days.
Title
PART 1 (PHASE 1): Clearance (CL) of gemcitabine (mL/kg/hr)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15. Each cycle is 28 days.
Title
PART 1 (PHASE 1): Presence of anti-drug antibody (ADA) and neutralizing antibodies (NAb) against PBP1510 administered as monotherapy, and in combination with gemcitabine.
Description
following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, End of Treatment (Day 57), Follow up (Day 72). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Trough concentration (Ctrough) of PBP1510 (µg/ml)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Peak concentration (Cmax) of PBP1510 (µg/ml)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Time to reach Cmax (Tmax) of PBP1510 (hr)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Terminal elimination half-life (t1/2) of PBP1510 (hr)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Area under the concentration-time curve (AUC) of PBP1510 (hr*µg /ml)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Mean residence time (MRT) of PBP1510 (hr)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Volume of distribution at steady state (Vss) of PBP1510 (mL/kg)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Volume of the central compartment (Vc) of PBP1510 (mL/kg)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Clearance (CL) of PBP1510 (mL/kg/hr)
Description
administered in combination with gemcitabine, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15, End of Treatment (Day 113). Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Trough concentration (Ctrough) of Gemcitabine (µg/ml)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15. Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Peak concentration (Cmax) of Gemcitabine (µg/ml)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15. Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Time to reach Cmax (Tmax) of Gemcitabine (hr)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15. Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Terminal elimination half-life (t1/2) of Gemcitabine (hr)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15. Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Area under the concentration-time curve (AUC) of Gemcitabine (hr*µg /ml)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15. Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Mean residence time (MRT) of Gemcitabine (hr)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15. Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Clearance (CL) of Gemcitabine (mL/kg/hr)
Description
administered in combination with PBP1510, following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 8, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 8, Cycle 4 Day 15. Each cycle is 28 days.
Title
PART 2 (PHASE 2a): Progression-free survival (PFS) after treatment with PBP1510 administered in combination with gemcitabine
Description
in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
6 months after end of treatment
Title
PART 2 (PHASE 2a): Overall Survival (OS) after treatment with PBP1510 administered in combination with gemcitabine
Description
in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
From the first PBP1510 infusion to the date of death due to any cause, for 6 months after end of treatment
Title
PART 2 (PHASE 2a): Duration of Response (DoR) after treatment with PBP1510 administered in combination with gemcitabine
Description
in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
from the first documentation of overall response (CR or PR) post first PBP1510 infusion to the first documentation of disease progression or death from any cause, for 6 months after end of treatment
Title
PART 2 (PHASE 2a): Presence of ADA and NAb against PBP1510 administered in combination with gemcitabine.
Description
following IV administration, in patients with pancreatic cancer whose tumours have progressed after one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, End of Treatment (Day 113). Each cycle is 28 days.
Other Pre-specified Outcome Measures:
Title
PART 1 (PHASE 1) Exploratory Endpoint: Preliminary evidence of clinical outcomes as assessed by objective response rate (ORR) after 2 cycles of treatment with PBP1510 administered as monotherapy, and in combination with gemcitabine.
Description
following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Title
PART 1 (PHASE 1) Exploratory Endpoint: Analysis of PAUF in tumour tissue pre-treatment and after 2 cycles of PBP1510 administered as monotherapy, and in combination with gemcitabine.
Description
following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Title
PART 2 (PHASE 2a) Exploratory Endpoint: Pre-treatment PAUF expression and clinical efficacy outcome after treatment with PBP1510 administered in combination with gemcitabine.
Description
following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
At the end of Cycle 4 (each cycle is 28 days)
Title
PART 2 (PHASE 2a) Exploratory Endpoint: Analysis of PAUF in tumour tissue pre-treatment and after 4 cycles of treatment with PBP1510 administered in combination with gemcitabine.
Description
following IV administration, in patients with pancreatic cancer whose tumours have progressed after at least one previous line of chemotherapy for locally advanced/metastatic disease.
Time Frame
At the end of Cycle 4 (each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients enrolling into Part 1 (Phase 1), or Part 2 (Phase 2a) must meet all of the following inclusion criteria: Adults ≥ 18 years of age (or the legal age of majority in the country of recruitment) at the time consent is obtained. Patient should understand, voluntarily sign, and date the written consent form prior to any protocol-specific procedures. Performance Status score less than or equal to 1 according to the Eastern Cooperative Oncology Group (ECOG) scale. Have histological or cytological evidence of a diagnosis of pancreatic cancer that is advanced and/or metastatic. Have a life expectancy of ≥ 3 months. No other malignancy present that would interfere with the current intervention. Prior radiation therapy for treatment of cancer is allowed to < 25% of the bone marrow, and patients must have recovered from the acute toxic effects of their treatment prior to study enrolment. Prior radiotherapy must be completed at least 4 weeks before the first dose of study treatment. At least one measurable lesion as per RECIST v1.1 Adequate baseline organ function defined as: ANC ≥ 1.5 × 10^9 /L; Haemoglobin ≥ 9 g/dL; Platelets ≥ 100 × 10^9 /L; Total bilirubin ≤ 2 × ULN (≤ 3 x ULN for patients with biliary stenting and patients with Gilbert's syndrome); AST and ALT < 3 x ULN (≤ 5 x ULN for patients with hepatic metastases); Serum creatinine OR creatinine clearance (as determined by the Cockcroft Gault formula) OR eGFR based on MDRD ≤ 1.5 x ULN OR ≥ 50 mL/min OR ≥ 50 mL/min/1.73 m^2; LVEF ≥ 50% by ECHO or MUGA; QTc ≤ 470 ms Female patients of nonchildbearing potential must meet at least 1 of the following criteria: have undergone a documented hysterectomy, and/or bilateral oophorectomy; have medically confirmed ovarian failure or achieved postmenopausal status. A postmenopausal state is defined as cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a follicle stimulating hormone (FSH) level confirming the postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. Female patients of childbearing potential must have a negative serum pregnancy test within 28 days prior to and negative urine pregnancy test just prior to the first dose of PBP1510 and agree to use effective contraception, in accordance with the recommendations of the Clinical Trials Facilitation and Coordination Group (CTFG) from study entry and until for at least 6 months after the last dose of PBP1510. For women of childbearing potential and men with partners of childbearing potential, agreement (by patient and/or partner) to use two effective forms of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) from study entry and until for at least 6 months after the last dose of PBP1510. Investigator or his/her representative should discuss acceptable pregnancy prevention method(s) with the patients. Highly effective methods of birth control include those that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, levonorgestrel-releasing intrauterine system, intra-uterine devices (IUDs), and true sexual abstinence. Patients must be willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures. Patients enrolling into Part 1 (Phase 1) of the study must also meet the following inclusion criteria: Monotherapy and combination cohorts: advanced/metastatic pancreatic cancer patients whose tumours have progressed after at least one prior line of standard chemotherapy. Patients enrolling into Part 2 (Phase 2a) of the study must also meet the following inclusion criteria: Advanced/metastatic pancreatic cancer patients whose tumours have progressed after one prior line of standard chemotherapy. Exclusion Criteria: Patients enrolling into Part 1 (Phase 1), or Part 2 (Phase 2a) will be excluded if any of the following criteria apply: Patients who have known brain metastases will be excluded from the study. However, a patient may be included in the study, if has been previously treated for brain metastasis, the disease is well controlled for at least 3 months, and the patient is off steroids. Patients who have undergone a major surgery within 4 weeks prior to the start of PBP1510 administration, other than endoscopic/radiation procedures, bypass surgery (i.e., gastrojejunostomy), laparoscopy, port placement or a diagnostic surgery (i.e., surgery done to obtain a diagnostic biopsy, without removal of an organ), as long as the patient has recovered from these minor surgical procedures. Patients who have active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, e.g., an active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii (P. carinii), or other microorganisms that is under treatment with myelotoxic drugs. Patient has a known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies). Patient has known history of or currently active hepatitis B (e.g., hepatitis B antigen [HBsAg] reactive), hepatitis C (e.g., HCV RNA [qualitative] is detected) or syphilis [Venereal Disease Research Laboratory (VDRL) to detect antibodies in blood]). Patient has impaired cardiac function and uncontrolled cardiac diseases/hypertension that are deemed clinically significant by the Investigator and which could compromise the patient's safety or the study data integrity. Patient has serious psychiatric disorders, which could compromise the patient's safety or the study data integrity. Any other malignancy from which the patient has been disease-free for less than 5 years, except for adequately treated and cured basal or squamous cell skin cancer. Patients who are enrolled in any other therapeutic clinical trial. Patients currently receiving radiation therapy or those having received radiation within 4 weeks prior to study entry. Patients having received investigational anti-cancer drug within 28 days (or 5 half-lives, whichever is longer) preceding the first dose of PBP1510 or chemotherapy within the last 4 weeks prior to the first dose of PBP1510. Patients with known allergy or hypersensitivity to components of the PBP1510 formulation including the excipients and history of hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies. Patients who are pregnant, or breast feeding. Patients who are unwilling or unable to comply with study procedures. Patients who are not eligible to participate in this study, as judged by Investigators. A history of allergic reactions attributed to gemcitabine or compounds of similar chemical composition to gemcitabine. Note: Patients with previous exposure to gemcitabine should not be excluded from the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Litha Jaison
Phone
+65-6924-6535
Email
litha.jaison@prestigebio.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jamie Kim
Phone
703 507 8050
Email
jamie.kim@prestigebio.com
Facility Information:
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jaime Feliu, MD PhD
Phone
+34917277516
Email
jaime.feliu@salud.madrid.org
First Name & Middle Initial & Last Name & Degree
Jaime Feliu, MD, PhD
First Name & Middle Initial & Last Name & Degree
Ismael Ghanem, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

First in Human Phase1/2a Clinical Trial of Anti-PAUF Monoclonal Antibody PBP1510 in Patients With Pancreatic Cancer

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