HRS 4642 Injection Combined With AG Versus Placebo Combined With AG Therapy in First-Line Advanced or Metastatic Pancreatic Cancer

a Randomized, Controlled, Double-Blind, Multicenter Phase III Clinical Trial of HRS-4642 in Combination With Chemotherapy Versus Placebo in Combination With Chemotherapy as First-Line Therapy in Patients With Advanced or Metastatic Pancreatic Carcinoma Harboring KRAS G12D Gene Mutation

This study investigates the first-line treatment of advanced pancreatic cancer with KRAS G12D mutation. Patients were randomized 1:1 to receive either the experimental regimen HRS-4642 plus AG or the control regimen AG alone.

Study Overview

• Status: Not yet recruiting
• Conditions: KRAS G12D-Mutant Advanced or Metastatic Pancreatic Cancer in the First-line Setting
• Intervention / Treatment: Drug: HRS-4642 + AG; Drug: HRS-4642 placebo + AG

• Study Type: Interventional
• Enrollment (Estimated): 588
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hongxia Han; Phone Number: +0518-81220121; Email: hongxia.han@hengrui.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200127
      • Renji Hospital, Shanghai Jiao Tong University School of Medicine
      • Principal Investigator: Liwei Wang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Able and willing to provide a written informed consent
2. Age 18-75 years old (inclusive) at the time of signing the informed consent form
3. Male or female
4. ECOG score of 0 or 1
5. Expected survival ≥ 12 weeks
6. At least one measurable lesion according to RECIST v1.1 criteria

Exclusion Criteria:

1. Any other condition that, in the judgment of the investigator, may increase the risk of participating in the study, interfere with the results of the study, or be unsuitable for participation in this study
2. Presence of uncontrollable psychiatric illness and other conditions such as known alcoholism, drug or substance abuse, criminal detention, etc., that affect the completion of the study procedures
3. Known hypersensitivity to any component of HRS-4642; History of severe allergic reactions to other monoclonal antibodies/fusion protein drugs; Known history of severe hypersensitivity to antineoplastic agents in combination
4. Received other major surgery other than diagnosis or biopsy within 28 days before the first dose; Minor traumatic surgery (biopsy, laparoscopy, and drainage) within 7 days prior to the first dose; Presence of non-healing wounds (severe, non-healing, or dehiscence), untreated fractures
5. Subjects who are participating in other clinical studies or whose first dose is less than 4 weeks from the end of the previous clinical study (last dose), or who have 5 half-lives of this investigational drug, whichever is shorter
6. Use of a live attenuated vaccine within 28 days prior to the first dose of study medication, or anticipated need for a live attenuated vaccine during study treatment
7. Have a history of immunodeficiency, including a positive HIV test, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation
8. Those who have active pulmonary tuberculosis infection within 1 year before enrollment, or those who have a history of active pulmonary tuberculosis infection more than 1 year ago but have not been formally treated
9. Active hepatitis B
10. Presence of clinically significant acute or chronic pancreatitis
11. Poorly controlled or severe cardiovascular and cerebrovascular diseases, arterior/venous thrombotic events within 6 months prior to study entry
12. Presence of gastrointestinal obstruction or presence of symptoms and signs of gastrointestinal obstruction within 6 months prior to the start of study treatment, but screening can be performed if surgical treatment has been performed and the obstruction has been completely resolved

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HRS-4642 + AG	Drug: HRS-4642 + AG; HRS-4642 + AG
Active Comparator: HRS-4642 placebo + AG	Drug: HRS-4642 placebo + AG; HRS-4642 placebo + AG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
OS	up to 3 years
PFS as assessed by BICR per RECIST 1.1	up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
ORR,as assessed by BICR per RECIST v1.1	up to 2 years
DCR as assessed by BICR per RECIST v1.1	up to 2 years
DoR as assessed by BICR per RECIST v1.1	up to 2 years
PFS as assessed by the investigator per RECIST v1.1.	up to 2 years
ORRas assessed by the investigator per RECIST v1.1.	up to 2 years
DCR as assessed by the investigator per RECIST v1.1.	up to 2 years
DoR as assessed by the investigator per RECIST v1.1.	up to 2 years
Incidence and severity of adverse events (AEs) graded by NCI-CTCAE v5.0.	Twice a month，up to 2 years

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: HRS-4642-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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