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.

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

HRS-4642

Wei Shi

Caicun Zhou

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

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

Phase I Study to Evaluate the Safety ,Tolerability, and Pharmacokinetics of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation

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

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

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

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

Area under the plasma concentration-time curve.

Apparent volume of distribution during terminal phase after non-intravenous administration.

Apparent total clearance of the drug from plasma after oral administration.

Jiangsu HengRui Medicine Co., Ltd.

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Carboplatin

Pemetrexed

Cisplatin

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations.

For HRS-4642 in combination with SHR-A1921，for advanced solid tumors with KRAS G12D mutations.

administrated per dose level in which the patients are assigned

Adebrelimab

SHR-A1921

administered as prescribed by the investigator.

Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection

Caicun Zhou, Doctor

The study is being conducted to evaluate the safety, tolerability, and efficacy of HRS-4642 in combination with antitumor medicine in patients with advanced solid tumors harboring KRAS G12D mutation.

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

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

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation	NCT05533463	Advanced KRAS G...	HRS-4642	18 Years -	Jiangsu HengRui Medicine Co., Ltd.
A Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation	NCT06385678	Advanced KRAS G...	HRS-4642 Adebrelimab SHR-A1921 Pemetrexed Diso...	18 Years - 75 Years	Jiangsu HengRui Medicine Co., Ltd.
Phase I Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation	NCT05533463	Advanced KRAS G...	HRS-4642	18 Years -	Jiangsu HengRui Medicine Co., Ltd.

Spots Global Cancer Trial Database for advanced kras g12d mutant solid tumors