Exploratory Clinical Study of HRS-4642 Combined With Adebrelimab in the Treatment of Advanced Pancreatic Ductal Adenocarcinoma

A Single-center, Open-label, Exploratory Study of HRS-4642 Combined With Adebrelimab, or With Adebrelimab and Other Antitumor Agents in the Treatment of Advanced Pancreatic Ductal Adenocarcinoma

The study is being conducted to evaluate the safety, tolerability and efficacy of HRS-4642 combined with adebrelimab, or with adebrelimab and other antitumor agents in patients with advanced pancreatic ductal adenocarcinoma (PDAC).

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: HRS-4642; Drug: Adebrelimab; Drug: SHR-8068; Drug: Faminitib or bevacizumab

Detailed Description

This study is an open, single center, exploratory clinical trial aimed at evaluating the efficacy and safety of HRS-4642 combined with adebrelimab, or with adebrelimab and other antitumor agents in the treatment of patients with advanced PDAC.

This study experiment is divided into two stages: dose exploration stage and efficacy exploration stage. Additional arms may be added based on emerging data.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Si Shi; Phone Number: +86-021-64179375; Email: Shisi@fudanpci.org

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
      • Contact: XianJun Yu, M.D., Ph.D.; Phone Number: +86-21-6417-5590; Email: yuxianjun@fudanpci.org
      • Principal Investigator: Xianjun Yu, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients volunteered to participate in this study and signed informed consent;
2. Age: ≥18 and ≤75 years old, male or female;
3. Advanced (metastatic or unresectable) Pancreatic ductal adenocarcinoma; and subjects must have at least one measurable lesion as defined by RECIST v1.1;
4. With failure or absence of standard treatment, and progress within 6 months of adjuvant therapy can also be included in the study;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
6. Life expectancy ≥ 12 weeks;
7. Adequate marrow and organ function;
8. AE caused by previous anti-tumor therapy must be restored to ≤ level 1 (CTCAE v5.0) or a stable state evaluated by the researcher, except for hair loss (any level) and peripheral neuropathy of level 2;
9. Female participants of childbearing age must undergo a pregnancy test within one week before the start of the study medication, and the result is negative. They are willing to use a medically recognized and efficient contraceptive method during the study period and within three months after the last administration of the study medication; For male participants whose partners are women of childbearing age, they should agree to use effective methods of contraception during the study period and within 3 months after the last study administration;

Exclusion Criteria:

1. Known to be allergic to the investigational drug or any of its components;
2. Have other active malignancies within 5 years;
3. Systemic antitumor therapy was received 4 weeks before the start of the study, and palliative radiotherapy was completed within 14 days before the first dose;
4. Previously received allogeneic hematopoietic stem cell transplantation or organ transplantation;
5. Accompanied by untreated or active central nervous system (CNS) metastases;
6. Within 6 months prior to entering the study, patients with severe cardiovascular and cerebrovascular thromboembolism;
7. Hypertension with poor drug control (continuous increase in systolic blood pressure ≥ 150mm Hg or diastolic blood pressure ≥ 100mmHg);
8. Late stage patients with symptoms that have spread to the internal organs and are at risk of life-threatening complications in the short term;
9. With interstitial lung disease, non-infectious pneumonia, severe and uncontrolled internal medicine diseases, acute infections, recent history of major surgery (within 28 days or not yet recovered from side effects);
10. Participated in clinical trials of any drug or medical device within 4 weeks prior to the first administration;
11. With congenital or acquired immune deficiency, such as people infected with HIV, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C antibody positive, and HCV-RNA higher than the detection limit of the analytical method) or combined with hepatitis B and hepatitis C infection;
12. With any active autoimmune diseases or a history of autoimmune diseases;
13. Received systemic treatment with corticosteroids or other immunosuppressants within 2 weeks prior to the first medication;
14. High risk of pancreatitis, serum amylase and/or lipase concentrations ≥ 3 times ULN; who have a simple increase in lipase, will be considered for inclusion by the researchers;
15. Other situations that researchers believe should not be included.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dose escalation; HRS-4642+Adebrelimab	Drug: HRS-4642; Specified dose on specified days; Drug: Adebrelimab; Specified dose on specified days
Experimental: efficacy exploration-Arm1; HRS-4642+Adebrelimab	Drug: HRS-4642; Specified dose on specified days; Drug: Adebrelimab; Specified dose on specified days
Experimental: efficacy exploration-Arm2; HRS-4642	Drug: HRS-4642; Specified dose on specified days
Experimental: efficacy exploration-Arm3; HRS-4642 + Adebrelimab + SHR-8068	Drug: HRS-4642; Specified dose on specified days; Drug: Adebrelimab; Specified dose on specified days; Drug: SHR-8068; Specified dose on specified days
Experimental: efficacy exploration-Arm4; HRS-4642+Adebrelimab+Faminitib/Bevacizumab	Drug: HRS-4642; Specified dose on specified days; Drug: Adebrelimab; Specified dose on specified days; Drug: Faminitib or bevacizumab; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limited Toxicity (DLT)	A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness	Day 1 to Day 21 after the first combination therapy was administrated
Recommended phase II dose (RP2D)	RP2D will be determined on the basis of evaluation on safety and efficacy data in dose escalation stages.	Approximately 12 months
Objective Response Rate (ORR)	Evaluated by RECIST v1.1.	Up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	Evaluated by RECIST v1.1.	Up to approximately 12 months
Duration of Response (DOR)	Evaluated by RECIST v1.1.	Up to approximately 12 months
Progression Free Survival (PFS)	Time from the date of enrollment to of disease progression, or death of any cause, or date of lost follow-up, whichever comes first, otherwise subject data were censored at time last known disease free.	Up to approximately 12 months
Overall survival (OS)	Time from the date of enrollment to data of death from any cause, or date of lost follow-up, whichever comes first, and otherwise censored at time last known alive.	Up to approximately 12 months
Adverse events (AEs)	AEs are assessed by NCI-CTCAE v5.0	From the first drug administration to within 90 days for the last adebrelimab dose

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: May 19, 2024
• First Submitted That Met QC Criteria: May 19, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab
• Other Study ID Numbers: PANC-2nd-IIT-HRS4642-SHR1316

Drug and device information, study documents

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