A Study of GFH925 in Patients With Advanced Solid Tumors With KRAS G12C Mutations

Innovent Biologics

Status and phase: Completed; Phase 2; Phase 1

Conditions: KRAS G12C

Treatments: Drug: GFH925

Study type: Interventional

Funder types: Industry

Identifiers

NCT05005234

GFH925X1101

Details and patient eligibility

About

Phase Ia:

To evaluate the safety/tolerability of GFH925 in subjects with KRAS G12C-mutated advanced solid tumors; To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of GFH925.

Phase Ib:

To evaluate the efficacy of GFH925 in subjects with KRAS G12C mutant advanced colorectal cancer or other tumors.

Phase II:

To evaluate the efficacy of GFH925 in subjects with KRAS G12C mutant advanced non-small cell lung cancer (NSCLC).

Enrollment: 334 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Volunteer to participate in the study and sign the informed consent form.
2. Aged 18 years or older at the time of signing the informed consent form.
3. Subjects must have one measurable lesion (per RECIST 1.1).
4. Subjects with toxic reaction caused by prior anticancer therapy need to have recovered to baseline level (except residual alopecia) or ≤ Grade 1 (neurotoxicity ≤ Grade 2 acceptable).
5. Eastern Cooperative Oncology Group (ECOG) performance status score (PS) 0 ~ 1.
6. Expected survival ≥ 12 weeks.
7. Female subjects or male subjects of childbearing potential must take effective contraceptive measures from the time of signing the informed consent form to 30 days after the last dose of GFH925, or to 60 days after the last dose of cetuximab. Female subjects of childbearing potential should have a negative blood pregnancy test within 7 days (inclusive) prior to initiation of study treatment.
8. The investigators deem the subject able to communicate well, attend regular follow-up visits, and complete the study according to the protocol.

Exclusion criteria

1. Significant cardiovascular system disease.
2. Subjects with unstable brain metastases diagnosed by investigators.
3. Significant gastrointestinal diseases, such as intractable hiccup, nausea, vomiting, severe gastrointestinal ulcers, cirrhosis, active gastrointestinal bleeding, or other diseases that affect swallowing tablets or significantly affect oral drug absorption; subjects with severe portal hypertension caused by the presence of Budd-Chiari syndrome or portal emboli in subjects with liver cancer also need to be excluded.
4. Presence of serious acute or chronic infections.
5. Pregnant or lactating women.
6. Known allergy to the study drug or any component of its formulation.
7. Other conditions that the investigators consider inappropriate for participation in this study.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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334 participants in 1 patient group

GFH925

Experimental group

Description:

Phase Ia Dose Escalation Subjects with advanced NSCLC and gastrointestinal tumors will be enrolled in dose escalation cohorts based on Bayesian optimal interval (BOIN) design. Phase Ia Dose Expansion Upon completing the dose exploration part of the study and depending on data obtained, dose expansion may proceed with responsive groups consisting of subjects with KRAS G12C mutant advanced NSCLC. Dose expansion may be done concurrently. Phase Ib Subjects with KRAS G12C mutant advanced colorectal cancer or other tumors will be enrolled and treated at the monotherapy RP2D to evaluate the efficacy. Phase 2 Subjects with KRAS G12C mutant advanced NSCLC will be enrolled and treated at the monotherapy RP2D to evaluate the safety and efficacy.

Treatment:

Drug: GFH925