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

Sponsor

Innovent Biologics (Suzhou) Co. Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05504278

Collaborator

(none)

144

Enrollment

Location

Arms

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Non-Small Cell Lung Cancer	Drug: pemetrexed Drug: Cetuximab Drug: cis-platinum Drug: Sintilimab Drug: IBI351 Drug: carboplatin	Phase 1

Detailed Description

This Phase Ib/III study evaluates the efficacy and safety of IBI351 in combination with Sintilimab± chemotherapy. There will be four cohorts of subjects, all of whom have KRAS G12C mutation and have advanced or metastatic NSCLC. Three cohorts (A, C and D) are treated with IBI351+Sintilimab, IBI351+Sintilimab+pemetrexed, or IBI351+Sintilimab+pemetrexed+cis-platinum/carboplatin, respectively, as first-line therapy. Cohort B enrolles subjects who is intolerant or has failed in standard-of care treatment,and is treated with IBI351+Cetuximab.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label, Multi-center Phase Ib/III Study Evaluating the Efficacy and Safety of IBI351 in Combination With Sintilimab ± Chemotherapy in Advanced Non-squamous Non-small Cell Lung Cancer Subjects With KRAS G12C Mutation

Anticipated Study Start Date :

Aug 31, 2022

Anticipated Primary Completion Date :

May 12, 2023

Anticipated Study Completion Date :

Jul 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IBI351 in combination with Sintilimab and pemetrexed	Drug: pemetrexed 500mg/m^2, Q3W, day1, i.v. Drug: Sintilimab 200mg, Q3W, day1, i.v. Other Names: IBI308 Drug: IBI351 recommended dose, po Other Names: GFH925
Experimental: IBI351 in combination with Sintilimab pemetrexed and cis-platinum/carboplatin	Drug: pemetrexed 500mg/m^2, Q3W, day1, i.v. Drug: cis-platinum 75mg/m^2, Q3W, day1, i.v. Drug: Sintilimab 200mg, Q3W, day1, i.v. Other Names: IBI308 Drug: IBI351 recommended dose, po Other Names: GFH925 Drug: carboplatin AUC=5, Q3W, day1, i.v.
Experimental: IBI351 in combination with Cetuximab	Drug: Cetuximab 400mg/m^2 C1D1, then 250mg/m^2 QW, i.v. Or, 500mg/m^2 Q2W, i.v. Drug: IBI351 recommended dose, po Other Names: GFH925
Experimental: IBI351 in combination with Sintilimab	Drug: Sintilimab 200mg, Q3W, day1, i.v. Other Names: IBI308 Drug: IBI351 recommended dose, po Other Names: GFH925

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Evaluate plasma peak concentration of IBI351 [12 months]
Cmax
Evaluate area under the plasma concentration-time curve (AUC) of IBI351 [12 months]
AUC
Evaluate terminal half-life (t1/2) of IBI351 [12 months]
t1/2
Evaluate clearance of IBI351 from the plasma [12 months]
CL/F
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 treatment-related adverse events [24 months]
TRAE
Number of subjects with serious adverse events [24 months]
SAE
Number of subjects with treatment-emergent adverse events [24 months]
TEAE

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of nonsquamous NSCLC with KRAS G12C mutation
Unresectable or metastatic disease
Adequate organ function

Exclusion Criteria:

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