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QUILT-3.060: NANT Pancreatic Cancer Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy

Primary Purpose

Pancreatic Cancer

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ALT-803
ETBX-011
GI-4000
haNK for infusion
avelumab
bevacizumab
Capecitabine
Cyclophosphamide
Fluorouracil
Leucovorin
nab-Paclitaxel
lovaza
Oxaliplatin
SBRT
Sponsored by
ImmunityBio, Inc.
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:

  1. Age ≥ 18 years old.
  2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
  3. Histologically-confirmed pancreatic cancer with progression on or after SoC therapy.
  4. ECOG performance status of 0 to 2.
  5. Have at least 1 measurable lesion of ≥ 1.5 cm.
  6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen following the conclusion of the most recent anticancer treatment and be willing to release the specimen. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period, if considered safe by the Investigator. If safety concerns preclude collection of a biopsy during the screening period, a tumor biopsy specimen collected prior to the conclusion of the most recent anticancer treatment may be used.
  7. Must be willing to provide blood samples prior to the start of treatment on this study.
  8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment, if considered safe by the Investigator.
  9. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  10. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence.

Exclusion Criteria:

  1. History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity resulting from previous therapy.
  2. Within 5 years prior to first dose of study treatment, any evidence of other active malignancies or brain metastasis except controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature.
  3. Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
  4. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
  5. History of organ transplant requiring immunosuppression.
  6. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  7. Requires whole blood transfusion to meet eligibility criteria.
  8. Inadequate organ function, evidenced by the following laboratory results:

    1. White blood cell (WBC) count < 3,500 cells/mm3
    2. Absolute neutrophil count < 1,500 cells/mm3.
    3. Platelet count < 100,000 cells/mm3.
    4. Hemoglobin < 9 g/dL.
    5. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
    6. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    7. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
    8. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
  9. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.
  10. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  11. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
  12. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
  13. Known hypersensitivity to any component of the study medication(s).
  14. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  15. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1.
  16. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
  17. Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer.
  18. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  19. Concurrent participation in any interventional clinical trial.
  20. Pregnant and nursing women.

Sites / Locations

  • Chan Soon-Shiong Institute for Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NANT Pancreatic Cancer Vaccine

Arm Description

A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT

Outcomes

Primary Outcome Measures

Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Phase 1b primary endpoint
Objective response rate by RECIST
Phase 2 primary endpoint

Secondary Outcome Measures

Objective response rate by RECIST
Phase 1b secondary endpoint
Progression-free survival by RECIST during Phase 1b
Phase 1b secondary endpoint
Progression-free survival by irRC during Phase 1b
Phase 1b secondary endpoint
Overall survival
Phase 1b secondary endpoint
Duration of response
Phase 1b secondary endpoint
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months).
Phase 1b secondary endpoint
Patient-reported outcomes of pancreatic cancer symptoms
Phase 1b secondary endpoint
Progression-free survival by RECIST during Phase 2
Phase 2 secondary endpoint
Progression-free survival by irRC during Phase 2
Phase 2 secondary endpoint
Overall survival
Phase 2 secondary endpoint
Duration of response
Phase 2 secondary endpoint
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months).
Phase 2 secondary endpoint
Patient-reported outcomes of pancreatic cancer symptoms
Phase 2 secondary endpoint

Full Information

First Posted
October 30, 2017
Last Updated
August 10, 2020
Sponsor
ImmunityBio, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03329248
Brief Title
QUILT-3.060: NANT Pancreatic Cancer Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy
Official Title
NANT Pancreatic Cancer Vaccine: Molecularly Informed Integrated Immunotherapy Combining Innate High-affinity Natural Killer (haNK) Cell Therapy With Adaptive T-cell Therapy (Adenovirus, Yeast, Fusion Protein Vaccine) in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 6, 2017 (Actual)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ImmunityBio, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with pancreatic cancer who have progressed on or after previous SoC chemotherapy. Phase 2 will be based on Simon's two-stage optimal design.
Detailed Description
Treatment will be administered in two phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects may remain on the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. The maximum time on study treatment, including both the induction and maintenance phases, is 2 years.

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
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NANT Pancreatic Cancer Vaccine
Arm Type
Experimental
Arm Description
A combination of agents will be administered to subjects in this study: ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, oxaliplatin, SBRT
Intervention Type
Biological
Intervention Name(s)
ALT-803
Intervention Description
Recombinant human super agonist interleukin-15 (IL-15) complex
Intervention Type
Biological
Intervention Name(s)
ETBX-011
Intervention Description
Ad5 [E1-, E2b-]-CEA
Intervention Type
Biological
Intervention Name(s)
GI-4000
Intervention Description
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins
Intervention Type
Biological
Intervention Name(s)
haNK for infusion
Intervention Description
NK-92 [CD16.158V, ER IL-2]
Intervention Type
Biological
Intervention Name(s)
avelumab
Intervention Description
Recombinant human anti-PD-L1 IgG1 monoclonal antibody
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Description
Recombinant human anti-VEGF IgG1 monoclonal
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Intervention Description
5-fluoro-2,4 (1H,3H)-pyrimidinedione
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
L-Glutamic acid, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-, calcium salt
Intervention Type
Drug
Intervention Name(s)
nab-Paclitaxel
Intervention Description
Benzenepropanoic acid, β-(benzoylamino)-α-hydroxy-(2aR, 4S, 4aS, 6R, 9S, 11S, 12S, 12aR, 12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a, 3, 4, 4a, 5, 6, 9, 10, 11, 12, 12a, 12b-dodecahydro-4,11-dihydroxy-4a, 8, 13, 13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-y1ester,(αR,βS)-(9CI) bound to albumin
Intervention Type
Drug
Intervention Name(s)
lovaza
Intervention Description
Omega-3-acid ethyl esters
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)- O,O'] platinum
Intervention Type
Procedure
Intervention Name(s)
SBRT
Intervention Description
Stereotactic Body Radiation Therapy
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Description
Phase 1b primary endpoint
Time Frame
8 weeks
Title
Objective response rate by RECIST
Description
Phase 2 primary endpoint
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Objective response rate by RECIST
Description
Phase 1b secondary endpoint
Time Frame
8 weeks
Title
Progression-free survival by RECIST during Phase 1b
Description
Phase 1b secondary endpoint
Time Frame
8 weeks
Title
Progression-free survival by irRC during Phase 1b
Description
Phase 1b secondary endpoint
Time Frame
8 weeks
Title
Overall survival
Description
Phase 1b secondary endpoint
Time Frame
8 weeks
Title
Duration of response
Description
Phase 1b secondary endpoint
Time Frame
1 year
Title
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months).
Description
Phase 1b secondary endpoint
Time Frame
1 year
Title
Patient-reported outcomes of pancreatic cancer symptoms
Description
Phase 1b secondary endpoint
Time Frame
8 weeks
Title
Progression-free survival by RECIST during Phase 2
Description
Phase 2 secondary endpoint
Time Frame
1 year
Title
Progression-free survival by irRC during Phase 2
Description
Phase 2 secondary endpoint
Time Frame
1 year
Title
Overall survival
Description
Phase 2 secondary endpoint
Time Frame
1 year
Title
Duration of response
Description
Phase 2 secondary endpoint
Time Frame
1 year
Title
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months).
Description
Phase 2 secondary endpoint
Time Frame
1 year
Title
Patient-reported outcomes of pancreatic cancer symptoms
Description
Phase 2 secondary endpoint
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years old. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines. Histologically-confirmed pancreatic cancer with progression on or after SoC therapy. ECOG performance status of 0 to 2. Have at least 1 measurable lesion of ≥ 1.5 cm. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen following the conclusion of the most recent anticancer treatment and be willing to release the specimen. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period, if considered safe by the Investigator. If safety concerns preclude collection of a biopsy during the screening period, a tumor biopsy specimen collected prior to the conclusion of the most recent anticancer treatment may be used. Must be willing to provide blood samples prior to the start of treatment on this study. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment, if considered safe by the Investigator. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence. Exclusion Criteria: History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity resulting from previous therapy. Within 5 years prior to first dose of study treatment, any evidence of other active malignancies or brain metastasis except controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature. Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma). History of organ transplant requiring immunosuppression. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis). Requires whole blood transfusion to meet eligibility criteria. Inadequate organ function, evidenced by the following laboratory results: White blood cell (WBC) count < 3,500 cells/mm3 Absolute neutrophil count < 1,500 cells/mm3. Platelet count < 100,000 cells/mm3. Hemoglobin < 9 g/dL. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome). Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases). Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases). Serum creatinine > 2.0 mg/dL or 177 μmol/L. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed. Known hypersensitivity to any component of the study medication(s). Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1. Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol. Concurrent participation in any interventional clinical trial. Pregnant and nursing women.
Facility Information:
Facility Name
Chan Soon-Shiong Institute for Medicine
City
El Segundo
State/Province
California
ZIP/Postal Code
90245
Country
United States

12. IPD Sharing Statement

Learn more about this trial

QUILT-3.060: NANT Pancreatic Cancer Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy

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