Phase I Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation

NCT05533463 | Active Not Recruiting Phase 1

• 1 other identifier: HRS-4642-I-101
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The study is being conducted to evaluate the safety and tolerability of HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation.To estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose \[RP2D\]) within investigated subject population groups

Conditions

Advanced KRAS G12D Mutant Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Safety endpoints: adverse events(AEs), serious adverse events（SAEs）.

  Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0).

  24 months

• 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

  from day 1 to Day 21

• Maximum tolerated dose (MTD)

  Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of HRS-4642 treatment.

  From Day 1 to Day 21

• RP2D

  RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages.

  24 months

Secondary Outcomes (14)

• Number of Participants With Abnormal Laboratory Values

  24months.

• Number of subjects with clinically significant changes in ECOG, vital signs and physical examination.

  24months.

• Number of subjects with changes on ECG.

  24months.

• Efficacy endpoints: Overall response rate (ORR).

  24months.

• Efficacy endpoints: Duration of response (DoR).

  24 months.

Study Arms (1)

HRS-4642

EXPERIMENTAL

In Dose Escalation: HRS-4642 will be injected QW. Six dose levels are preset. In Dose Expansion: 1 to 2 dose cohorts will be selected for dose expansion stage. In Indication Expansion: Enrollment into the dose expansion cohorts may be from any eligible solid tumor type.

Drug: HRS-4642

Interventions

HRS-4642 DRUG

HRS-4642 will be administrated per dose level in which the patients are assigned.

HRS-4642

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
• Male or female ≥ 18 years old.
• Histologically confirmed diagnosis of advanced solid tumor harbouring with KRAS G12D mutation
• ECOG performance status of 0-1.
• With a life expectancy of ≥3 months.
• Have at least one measurable lesion.
• Adequate laboratory parameters during the screening period

You may not qualify if:

• Previously received KRAS G12D inhibitors
• Priot radiotherapy within 28 days for non-thoracic radiation
• Prior anti-tumor chemotherapy (\< 6 weeks if chemotherapy including nitrosoureas or mitomycin) within 4 weeks before the study drug administration
• Central nervous system (CNS) metastases
• Major surgical therapy within 28 days prior to the date of signature of informed consent form, or expected major surgery during the study.
• Known history of hypersensitivity to any components of HRS-4642.
• Other factors that may affect the study results or lead to forced termination of the study early as judged by investigators.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm study of HRS-4642

Study Record Dates

• First Submitted: September 5, 2022
• First Posted: September 9, 2022
• Study Start: September 21, 2022
• Primary Completion: June 25, 2024
• Study Completion: December 30, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

CN (1)