HRS-4642 combined with antineoplastic drugs for advanced KRAS G12D solid tumors

Phase IB/II Clinical Study of the Safety, Tolerability and Efficacy of HRS-4642 in Combination With Anti-tumor Agents in Subjects With Advanced Solid Tumors

This trial will test whether adding HRS-4642 to standard anti-cancer drugs is safe and shows early signs of benefit in adults with advanced solid tumors that have a KRAS G12D mutation.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 118 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. (industry)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06520488 on ClinicalTrials.gov

What this trial studies

This Phase 1/2, open-label trial uses a dose-escalation and expansion design to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of HRS-4642 given with antineoplastic agents in patients with KRAS G12D–mutant advanced solid tumors. Eligible adults must have measurable disease per RECIST v1.1 and an ECOG performance status of 0–1. Primary endpoints include safety, dose-limiting toxicities, and determination of MTD/RP2D, with secondary endpoints capturing preliminary efficacy such as response rate and progression measures. Patients will be closely monitored for adverse events and tumor response during treatment and follow-up.

Who should consider this trial

Good fit: Adults aged 18–75 with advanced solid tumors harboring a KRAS G12D mutation, ECOG 0–1, measurable disease, and expected survival of at least 12 weeks are the intended participants.

Not a fit: Patients with uncontrolled psychiatric illness, known severe hypersensitivity to HRS-4642 or the partner antineoplastic agents, or other serious comorbidities that increase risk or interfere with study procedures may not receive benefit from participation.

Why it matters

Potential benefit: If successful, this combination could provide a new targeted option that helps control tumor growth in patients with KRAS G12D–mutant advanced solid tumors.

How similar studies have performed: Direct clinical evidence for KRAS G12D–targeted therapies is limited, although KRAS-targeting approaches (notably for G12C) have shown clinical promise, so this specific combination remains largely untested in humans.

Eligibility criteria

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

Where this trial is running

Shanghai, Shanghai Municipality

• Renji Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Hongxia Han

Conditions: Advanced Solid Tumors