Newly Emerging Immunotherapy for Pancreatic Cancer Treatment (FD-IMPACT)

A Phase Ib/II Platform Trial of Newly Emerging Immunotherapy for Pancreatic Cancer Treatment

This is a Phase Ib/II platform clinical study to evaluate the initial efficacy and safety of different novel immunotherapies in patients with advanced pancreatic cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: JS001; Drug: JS004; Drug: Irinotecan Liposome Injection; Drug: 5-Fluorouracil (5-FU); Drug: Leucovorin (LV); Drug: JS007; Drug: JS015; Drug: Nab paclitaxel; Drug: Gemcitabine

Detailed Description

The cohort A/B/C included patients with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy.The cohort D/E/F included patients with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer.This study plans to first explore A/B/C cohort, and then start the D/E/F cohort after determining the safety.

• Study Type: Interventional
• Enrollment (Estimated): 117
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xianjun Yu, M.D.; Phone Number: +86-18017317266; Email: yuxianjun@fudanpci.org

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntary participation, written informed consent, complied well and cooperated with the follow-up visits;
• Age ≥ 18 years old, female or male individuals;
• Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1, the expected survival is more than 3 months;

• Patients with locally advanced unresectable or metastatic pancreatic cancer confirmed by histopathology or cytopathology (islet cell tumor is not eligible for inclusion) who meet the following requirements:

  • For the A/B/C/ cohort: Had failed of at least first-line systemic therapy; disease recurrence or progression within 6 months of the last treatment of neoadjuvant or adjuvant chemotherapy was also allowed to be enrolled;
  • For the D/E/F cohort: No prior systemic treatment; patients with recurrence or progression of disease more than 6 months after the last treatment of neoadjuvant or adjuvant chemotherapy were also allowed to be enrolled;
• Had at least one measurable lesion according to RECIST v1.1.
• Patients had adequate major organs function;
• Women of childbearing potential must undergo serum pregnancy test within 7 days prior to the first dose and the result must be negative. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug.

Exclusion Criteria:

• Previously received drugs with the same target as the planned investigational therapy;
• radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, immunotherapy, or molecular targeted therapy within 4 weeks prior to initial administration, except for bisphosphonates (which can be used for bone metastasis);
• Uncontrolled central nervous system metastases (meaning symptoms or the use of glucocorticoids or mannitol to control symptoms);
• A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmia, in the 6 months prior to initial dosing;
• Patients with Grade 1 and above adverse reactions caused by previous treatment, including Grade 1 peripheral neurotoxicity; hair loss is not included and the investigator should clearly record the reasons;
• Malignant tumors within 5 years prior to the first dose (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
• Active autoimmune disease requiring systemic treatment within 2 years prior to first administration, except for vitiligo, type I diabetes, residual hypothyroidism due to autoimmune thyroiditis requiring hormone replacement therapy only;
• History of rapid allergic reaction, eczema or asthma that cannot be controlled by topical corticosteroids;
• Patients who have lung disease, such as drug-induced interstitial lung disease or pneumonia, obstructive pulmonary disease that severely affects lung function, and symptomatic bronchospasm;
• Serious infections requiring antibiotic treatment within 14 days prior to initial administration (>CTCAE grade 2), such as severe pneumonia, bacteremia, comorbidifications, etc., resulting in the need for hospitalization;
• Vaccination of live vaccine within 4 weeks before the first dose or during the study period;
• Known human immunodeficiency virus (HIV) infection, allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• History of prior allergy to any component or excipient of the investigational drug to be received;
• Other conditions assessed by the investigator as unsuitable for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort1: JS004+JS001+Irinotecan Liposome Injection+5-fluorouracil (5-FU)/leucovorin (LV); Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS004 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.	Drug: JS001; 240 mg by IV infusionevery 3 weeks (Q3W), given on cycle day 1.; Other Names: Toripalimab; Drug: JS004; 200 mg by IV infusion Q3W, given on cycle day 1.; Drug: Irinotecan Liposome Injection; 60 or 70 mg/m^2 by IV infusion every 2 weeks (Q2W), given on cycle day 1.; Drug: 5-Fluorouracil (5-FU); 2400mg/m^2, intravenously, over 46 h on day 1, Q2W.; Drug: Leucovorin (LV); 400mg/m^2, intravenously, over 30 min on day 1, Q2W.
Experimental: Cohort2: JS007+JS001+Irinotecan Liposome Injection+5-FU/LV; Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS007 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.	Drug: JS001; 240 mg by IV infusionevery 3 weeks (Q3W), given on cycle day 1.; Other Names: Toripalimab; Drug: Irinotecan Liposome Injection; 60 or 70 mg/m^2 by IV infusion every 2 weeks (Q2W), given on cycle day 1.; Drug: 5-Fluorouracil (5-FU); 2400mg/m^2, intravenously, over 46 h on day 1, Q2W.; Drug: Leucovorin (LV); 400mg/m^2, intravenously, over 30 min on day 1, Q2W.; Drug: JS007; 3mg/kg by IV infusion Q3W, given on cycle day 1.
Experimental: Cohort3: JS015+JS001+Irinotecan Liposome Injection+5-FU/LV; Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS015 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.	Drug: JS001; 240 mg by IV infusionevery 3 weeks (Q3W), given on cycle day 1.; Other Names: Toripalimab; Drug: Irinotecan Liposome Injection; 60 or 70 mg/m^2 by IV infusion every 2 weeks (Q2W), given on cycle day 1.; Drug: 5-Fluorouracil (5-FU); 2400mg/m^2, intravenously, over 46 h on day 1, Q2W.; Drug: Leucovorin (LV); 400mg/m^2, intravenously, over 30 min on day 1, Q2W.; Drug: JS015; 600mg by IV infusion Q3W, given on cycle day 1.
Experimental: Cohort4: JS004+JS001+Nab-Paclitaxel+Gemcitabine; Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS004 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.	Drug: JS001; 240 mg by IV infusionevery 3 weeks (Q3W), given on cycle day 1.; Other Names: Toripalimab; Drug: JS004; 200 mg by IV infusion Q3W, given on cycle day 1.; Drug: Nab paclitaxel; 125 mg/m^2 by IV infusion Q3W, given on cycle day 1 and 8.; Drug: Gemcitabine; 1000 mg/m^2 by IV infusion Q3W, given on cycle day 1 and 8.
Experimental: Cohort5: JS007+JS001+Nab-Paclitaxel+Gemcitabine; Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS007 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.	Drug: JS001; 240 mg by IV infusionevery 3 weeks (Q3W), given on cycle day 1.; Other Names: Toripalimab; Drug: JS007; 3mg/kg by IV infusion Q3W, given on cycle day 1.; Drug: Nab paclitaxel; 125 mg/m^2 by IV infusion Q3W, given on cycle day 1 and 8.; Drug: Gemcitabine; 1000 mg/m^2 by IV infusion Q3W, given on cycle day 1 and 8.
Experimental: Cohort6: JS015+JS001+ Nab-Paclitaxel+Gemcitabine; Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS015 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.	Drug: JS001; 240 mg by IV infusionevery 3 weeks (Q3W), given on cycle day 1.; Other Names: Toripalimab; Drug: JS015; 600mg by IV infusion Q3W, given on cycle day 1.; Drug: Nab paclitaxel; 125 mg/m^2 by IV infusion Q3W, given on cycle day 1 and 8.; Drug: Gemcitabine; 1000 mg/m^2 by IV infusion Q3W, given on cycle day 1 and 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicity (DLT) (phase IB)	If less than 2 participants developed DLT during the safety observation period (one cycle after the first dose), follow-up first-line D/E/F cohort exploration should be considered. Otherwise, it is up to the investigator to decide the next research plan.	21 days after the first dose was administered to each subject
Objective Response Rate (ORR) (phase II)	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on RECIST 1.1.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) (phase IB)	ORR was defined as the percentage of participants with a best overall response of CR or PR based on RECIST 1.1.	Up to 1 year
Disease control rate (DCR)	DCR was defined as the percentage of cases with remission (PR + CR) and stable lesions (SD) after treatment was assessable based on RECIST 1.1.	Up to 1 year
Duration of Response (DOR)	DOR will be calculated from the date of the first evaluation showing PR, or CR, to the date of the first disease progression or death, whichever comes first and based on RECIST 1.1.	Up to 1 year
Progression free survival (PFS)	PFS is defined as the time from the first dose until objective tumor progression(PD), or death, whichever comes first and based on RECIST 1.1. At the end of the study, the time of last acquisition of living patients without PD was taken as the deleted data.	Up to 2 years
Overall Survival (OS)	OS will be measured from the date of first dose to death from any cause.	Up to 2 years
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment	Adverse event (AE), abnormal laboratory examination, serious adverse event (SAE) related with the study drug judged using NCI-CTCAE V5.0 by investigator.	90 days after the last administration

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Paclitaxel; Fluorouracil; Leucovorin; Irinotecan; Gemcitabine
• Other Study ID Numbers: 2401289-19-2403

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No