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IN10018+ Standard Chemotherapy (+KN046) in Subjects With Advanced Pancreatic Cancer

Primary Purpose

Pancreatic Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
IN10018
Albumin-Bound Paclitaxel
Gemcitabine
KN046
Sponsored by
InxMed (Shanghai) Co., Ltd.
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: With a full understanding of the study, each subject voluntarily agreed to participate in this study and sign the informed consent form. Female or male subjects ≥ 18 years at the time of signing informed consent. Histological or cytology-confirmed pancreatic ductal adenocarcinoma (including adenosquamous carcinoma). No previous systemic treatment for unresectable, locally advanced, or metastatic pancreatic cancer. At least one measurable lesion per RECIST 1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of at least 3 months as assessed by the investigator. Must have recovered from all AEs due to previous anticancer therapies to ≤ Grade 1 (CTCAE 5.0) or stable status as assessed by the investigator. Subjects with any grade of alopecia and grade 2 peripheral neuropathy could be enrolled. Adequate bone marrow, liver, renal, and coagulation function . A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) . or A WOCBP who agrees to follow the contraceptive guidance. Exclusion Criteria: Has had major surgery or major trauma within 28 days prior to the first dose of study treatment. Has known BRCA1/2 mutations. Has received prior systemic anticancer therapy including chemotherapy, targeted therapy, immunotherapy, unmarketed investigational drugs or therapy within 28 days prior to the first dose of study treatment. Previous anti-programmed death 1(PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody therapy, or any other antibody or drug that specifically targets T-cell co-stimulation or checkpoint pathways, or prior treatment with focal adhesion kinase (FAK) inhibitors. Has received radical radiotherapy within 3 months prior to the first dose of study treatment. Subjects who have received palliative radiotherapy with a local standardized dose within 2 weeks prior to the first dose of study treatment. Has received previous allogeneic hematopoietic stem cell transplantation or organ transplantation. Has received live vaccines and live attenuated vaccines within 28 days prior to the first dose of study treatment. Has interstitial pneumonia or lung disease. History or current active autoimmune diseases. Has a prior history of other malignancy, other than cured cutaneous squamous cell carcinoma, basal cell cancer, non-basal invasive bladder cancer, and prostate/cervical/breast cancer in situ within 5 years prior to the first dose of study treatment. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Has a history of major cardiovascular, cerebrovascular or thromboembolic diseases within 6 months before the first dose of study treatment. Active infection with poor systemic treatment control. Has known human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or hepatitis C (HCV) infection, or active syphilis and tuberculosis. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sites / Locations

  • Renji Hospital of Shanghai Jiaotong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1: IN10018+ standard chemotherapy (albumin-bound paclitaxel + gemcitabine)

Cohort 2: IN10018+ standard chemotherapy (albumin-bound paclitaxel + gemcitabine)+KN046

Arm Description

Subjects will be treated with IN10018 25 mg/50 mg/100 mg, once daily, oral+ albumin-bound paclitaxel 125 mg/m2 IV infusion on Days 1 and 8 of each 21-Day Cycle+ gemcitabine 1000 mg/m2 IV infusion on Days 1 and 8 of each 21-Day Cycle.

Subjects will be treated with IN10018 25 mg/50 mg/100 mg, once daily, oral+ albumin-bound paclitaxel 125 mg/m2 IV infusion on Days 2 and 8 of each 21-Day Cycle+ gemcitabine 1000 mg/m2 IV infusion on Days 2 and 9 of each 21-Day Cycle+KN046 5 mg/kg IV infusion on Day 1 of each 21-Day Cycle.

Outcomes

Primary Outcome Measures

Incidence of Treatment-Related Adverse Events (AEs)
Incidence and severity of AEs, with severity determined according to the NationalCancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
To evaluate the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in subjects with advanced pancreatic cancer.
Proportion of subjects who have the best objective response of either complete response (CR) or partial response (PR), as assessed by the investigator.

Secondary Outcome Measures

Disease Control Rate (DCR) per RECIST 1.1, as evaluated by investigators
Proportion of subjects who have CR, PR, or stable disease (SD).
duration of response (DoR) per RECIST 1.1, as evaluated by investigators
Available for subjects who demonstrate CR or PR, DoR is defined as the time from the first evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, as assessed by the investigator.
Progression free survival (PFS) per RECIST 1.1, as evaluated by investigators
Defined as the time from the first day of study treatment to the first disease progression or death due to any cause, whichever occurs first.
Overall survival (OS)
Defined as the time from the first day of study treatment to death due to any cause.
Incidence of Treatment-Related AEs
Incidence and severity of AEs, with severity determined according to the NCI CTCAE v5.0

Full Information

First Posted
March 28, 2023
Last Updated
April 23, 2023
Sponsor
InxMed (Shanghai) Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05827796
Brief Title
IN10018+ Standard Chemotherapy (+KN046) in Subjects With Advanced Pancreatic Cancer
Official Title
A Phase Ib/II, Open-label Clinical Study to Evaluate the Safety, Tolerability and Antitumor Activities of IN10018+Standard Chemotherapy and IN10018+Standard Chemotherapy+KN046 in Subjects With Advanced Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 8, 2022 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
InxMed (Shanghai) Co., Ltd.

4. Oversight

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

5. Study Description

Brief Summary
This study is a multicenter, open-label, single-arm, phase Ib/II clinical study comprising two phases: dose confirmation phase and dose expansion phase. The objective of the dose confirmation phase is to determine the recommended Phase II dose (RP2D) of IN10018+ standard chemotherapy (albumin-bound paclitaxel + gemcitabine) and IN10018 + KN046 + standard chemotherapy in subjects with advanced pancreatic cancer. The dose expansion phase will further explore the antitumor activities and safety of combination therapy in subjects with advanced pancreatic cancer.
Detailed Description
This is a multicenter, open-label, single-arm, phase Ib/II clinical study to evaluate the safety, tolerability, and antitumor activities of IN10018 + standard chemotherapy (albumin paclitaxel + gemcitabine) and IN10018 + KN046 + standard chemotherapy in subjects with advanced pancreatic cancer. This study includes two cohorts, Cohort 1: IN10018 + standard chemotherapy; Cohort 2: IN10018 + standard chemotherapy + KN046. Each cohort consists of 2 phases: a dose confirmation phase and a dose expansion phase. The dose confirmation phase aims to determine recommended Phase II dose (RP2D) of IN10018+ standard chemotherapy and IN10018 + KN046 + standard chemotherapy in subjects with advanced pancreatic cancer. The dose expansion phase will further explore the antitumor activities and safety of combination therapy in subjects with advanced pancreatic cancer. According to the Package Insert of standard chemotherapy (albumin paclitaxel and gemcitabine), the Investigator's Brochure (IB) and drug characteristics of KN046, it is expected that IN10018 has little possibility of interaction with standard chemotherapy and KN046, and the safety characteristics are clearly non-overlapping. The therapeutic dose of KN046, albumin-bound paclitaxel and gemcitabine are fixed in this study. In the dose confirmation phase, IN10018 dose will be modified according to the causality between dose-limiting toxicities (DLTs) and IN10018.

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
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: IN10018+ standard chemotherapy (albumin-bound paclitaxel + gemcitabine)
Arm Type
Experimental
Arm Description
Subjects will be treated with IN10018 25 mg/50 mg/100 mg, once daily, oral+ albumin-bound paclitaxel 125 mg/m2 IV infusion on Days 1 and 8 of each 21-Day Cycle+ gemcitabine 1000 mg/m2 IV infusion on Days 1 and 8 of each 21-Day Cycle.
Arm Title
Cohort 2: IN10018+ standard chemotherapy (albumin-bound paclitaxel + gemcitabine)+KN046
Arm Type
Experimental
Arm Description
Subjects will be treated with IN10018 25 mg/50 mg/100 mg, once daily, oral+ albumin-bound paclitaxel 125 mg/m2 IV infusion on Days 2 and 8 of each 21-Day Cycle+ gemcitabine 1000 mg/m2 IV infusion on Days 2 and 9 of each 21-Day Cycle+KN046 5 mg/kg IV infusion on Day 1 of each 21-Day Cycle.
Intervention Type
Drug
Intervention Name(s)
IN10018
Other Intervention Name(s)
BI853520
Intervention Description
IN10018 orally once daily at approximately the same time each day, to ensure a dosing interval of approximately 24 hours.
Intervention Type
Drug
Intervention Name(s)
Albumin-Bound Paclitaxel
Intervention Description
Albumin-bound paclitaxel will be administered as per the schedule specified in the respective arm.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Gemcitabine will be administered as per the schedule specified in the respective arm.
Intervention Type
Drug
Intervention Name(s)
KN046
Intervention Description
KN046 5 mg/kg on Day 1 of each 21-Day Cycle.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Related Adverse Events (AEs)
Description
Incidence and severity of AEs, with severity determined according to the NationalCancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Time Frame
1 year
Title
To evaluate the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in subjects with advanced pancreatic cancer.
Description
Proportion of subjects who have the best objective response of either complete response (CR) or partial response (PR), as assessed by the investigator.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Disease Control Rate (DCR) per RECIST 1.1, as evaluated by investigators
Description
Proportion of subjects who have CR, PR, or stable disease (SD).
Time Frame
1 year
Title
duration of response (DoR) per RECIST 1.1, as evaluated by investigators
Description
Available for subjects who demonstrate CR or PR, DoR is defined as the time from the first evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, as assessed by the investigator.
Time Frame
1 years
Title
Progression free survival (PFS) per RECIST 1.1, as evaluated by investigators
Description
Defined as the time from the first day of study treatment to the first disease progression or death due to any cause, whichever occurs first.
Time Frame
1 years
Title
Overall survival (OS)
Description
Defined as the time from the first day of study treatment to death due to any cause.
Time Frame
2 years
Title
Incidence of Treatment-Related AEs
Description
Incidence and severity of AEs, with severity determined according to the NCI CTCAE v5.0
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: With a full understanding of the study, each subject voluntarily agreed to participate in this study and sign the informed consent form. Female or male subjects ≥ 18 years at the time of signing informed consent. Histological or cytology-confirmed pancreatic ductal adenocarcinoma (including adenosquamous carcinoma). No previous systemic treatment for unresectable, locally advanced, or metastatic pancreatic cancer. At least one measurable lesion per RECIST 1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of at least 3 months as assessed by the investigator. Must have recovered from all AEs due to previous anticancer therapies to ≤ Grade 1 (CTCAE 5.0) or stable status as assessed by the investigator. Subjects with any grade of alopecia and grade 2 peripheral neuropathy could be enrolled. Adequate bone marrow, liver, renal, and coagulation function . A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) . or A WOCBP who agrees to follow the contraceptive guidance. Exclusion Criteria: Has had major surgery or major trauma within 28 days prior to the first dose of study treatment. Has known BRCA1/2 mutations. Has received prior systemic anticancer therapy including chemotherapy, targeted therapy, immunotherapy, unmarketed investigational drugs or therapy within 28 days prior to the first dose of study treatment. Previous anti-programmed death 1(PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody therapy, or any other antibody or drug that specifically targets T-cell co-stimulation or checkpoint pathways, or prior treatment with focal adhesion kinase (FAK) inhibitors. Has received radical radiotherapy within 3 months prior to the first dose of study treatment. Subjects who have received palliative radiotherapy with a local standardized dose within 2 weeks prior to the first dose of study treatment. Has received previous allogeneic hematopoietic stem cell transplantation or organ transplantation. Has received live vaccines and live attenuated vaccines within 28 days prior to the first dose of study treatment. Has interstitial pneumonia or lung disease. History or current active autoimmune diseases. Has a prior history of other malignancy, other than cured cutaneous squamous cell carcinoma, basal cell cancer, non-basal invasive bladder cancer, and prostate/cervical/breast cancer in situ within 5 years prior to the first dose of study treatment. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Has a history of major cardiovascular, cerebrovascular or thromboembolic diseases within 6 months before the first dose of study treatment. Active infection with poor systemic treatment control. Has known human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or hepatitis C (HCV) infection, or active syphilis and tuberculosis. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bohong Zhang
Phone
+86 18801955197
Email
bohong.zhang@inxmed.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liwei Wang
Organizational Affiliation
Renji Hospital of Shanghai Jiaotong University of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Renji Hospital of Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liwei Wang
Phone
+86 13761254228
Email
lwwang2013@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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IN10018+ Standard Chemotherapy (+KN046) in Subjects With Advanced Pancreatic Cancer

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