Efficacy and Safety of IBI351 in Combination With Chemotherapy in Advanced Non-squamous Non-small Cell Lung Cancer Subjects With KRAS G12C Mutation

Phase 1

Recruiting

• Conditions: Advanced Non-Small Cell Lung Cancer
• Interventions: Drug: IBI351; Drug: Sintilimab; Drug: pemetrexed; Drug: Cetuximab; Drug: Carboplatin; Drug: cis-platinum

• Registration Number: NCT05504278
• Lead Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Brief Summary

This Phase Ib/III study evaluates the efficacy and safety of IBI351 in combination with chemotherapy in advanced non-squamous NSCLC with KRAS G12C mutation.

Detailed Description

This Phase Ib/III study evaluates the efficacy and safety of IBI351 in combination with chemotherapy. There will be five cohorts of subjects, all of whom have KRAS G12C mutation and have advanced or metastatic NSCLC. Those five cohorts (A, B,C ,D and E) are treated with IBI351, IBI351+Sintilimab,IBI351+pemetrexed+cis-platinum/carboplatin,IBI351+Cetuximab, or IBI351+pemetrexed+cis-platinum/carboplatin respectively.

IBI351 is an orally available small molecule inhibitor of KRAS G12C.

Study Timeline

• Study First Submitted: 2022-08-11
• Study First Submitted QC: 2022-08-15
• Study First Posted: 2022-08-17
• Study Start: 2022-09-20
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-05-31
• Study Completion: 2027-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

1. Histologically confirmed diagnosis of nonsquamous NSCLC with KRAS G12C mutation
2. Unresectable or metastatic disease
3. Adequate organ function
4. Not received any systemic antitumor therapy for locally advanced or metastatic non-squamous NSCLC previously.

Exclusion Criteria

1. History of intestinal disease or major gastric surgery or inability to swallow oral medications
2. Prior therapy with agents targeting KRAS G12C mutation (e.g., AMG 510).
3. Active brain metastases.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IBI351 in combination with Sintilimab	Sintilimab	-
IBI351 in combination with pemetrexed and cis-platinum/carboplatin (the subject with PD-L1 TPS<1%)	pemetrexed	-
IBI351 monotherapy	IBI351	-
IBI351 in combination with pemetrexed and cis-platinum/carboplatin (the subject with PD-L1 TPS<1%)	Carboplatin	-
IBI351 in combination with pemetrexed and cis-platinum/carboplatin (the subject with PD-L1 TPS<1%)	cis-platinum	-
IBI351 in combination with Cetuximab	Cetuximab	-
IBI351 in combination with pemetrexed and cis-platinum/carboplatin(the subject with PD-L1 TPS 1-49%)	pemetrexed	-
IBI351 in combination with pemetrexed and cis-platinum/carboplatin(the subject with PD-L1 TPS 1-49%)	Carboplatin	-
IBI351 in combination with pemetrexed and cis-platinum/carboplatin(the subject with PD-L1 TPS 1-49%)	cis-platinum	-
IBI351 in combination with Sintilimab	IBI351	-
IBI351 in combination with pemetrexed and cis-platinum/carboplatin (the subject with PD-L1 TPS<1%)	IBI351	-
IBI351 in combination with Cetuximab	IBI351	-
IBI351 in combination with pemetrexed and cis-platinum/carboplatin(the subject with PD-L1 TPS 1-49%)	IBI351	-

Primary Outcome Measures

Name	Time	Method
Number of participants with dose limiting toxicity	12 months	Number of participants with dose limiting toxicity in the dose escalation period
Evaluate clinical efficacy of IBI351 in combination with other therapeutic agents	24 months	Objective response rate per RECIST v1.1
Safety indicators during the introduction phase for IBI351 combination treatment :	24 months	Number of participants with Adverse events (AE), Treatment Emergent Adverse events (TEAE), treatment-related Adverse events (TEAE), TRAE) and the incidence of Serious Adverse events (SAE) (CTCAE v5.0 standard), with abnormal vital signs, abnormal physical exams, abnormal laboratory results and abnormal 12-lead electrocardiogram

Secondary Outcome Measures

Name	Time	Method
Number of subjects with treatment-emergent adverse events	24 months	TEAE
Overall Survival	24 months	OS
Evaluate area under the plasma concentration-time curve (AUC) of IBI351	12 months	AUC
Evaluate clearance of IBI351 from the plasma	12 months	CL/F
Number of subjects with treatment-related adverse events	24 months	TRAE
Evaluate plasma peak concentration of IBI351	12 months	Cmax
Evaluate terminal half-life (t1/2) of IBI351	12 months	t1/2
Evaluate distribution of IBI351	12 months	V/F
Evaluate clinical efficacy of IBI351 in combination with other therapeutic agents with other index	24 months	PFS, DCR,DOR, TTR per RECIST v1.1; OS
Number of subjects with adverse events of interest	24 months	AE
Number of subjects with serious adverse events	24 months	SAE

Trial Locations

Locations (1)

Jilin Province Cancer Hospital; 🇨🇳 Jilin, Changchun, China