An Open-label, Multi-center Phase Ib/III Study Evaluating the Efficacy and Safety of IBI351 in Combination With Chemotherapy in Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Subjects With KRAS G12C Mutation
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 144
- Locations
- 1
- Primary Endpoint
- Number of participants with dose limiting toxicity
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed diagnosis of nonsquamous NSCLC with KRAS G12C mutation
- •Unresectable or metastatic disease
- •Adequate organ function
- •Not received any systemic antitumor therapy for locally advanced or metastatic non-squamous NSCLC previously.
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.
Arms & Interventions
IBI351 in combination with pemetrexed and cis-platinum/carboplatin (the subject with PD-L1 TPS<1%)
Intervention: IBI351 (Drug)
IBI351 in combination with pemetrexed and cis-platinum/carboplatin (the subject with PD-L1 TPS<1%)
Intervention: pemetrexed (Drug)
IBI351 in combination with pemetrexed and cis-platinum/carboplatin (the subject with PD-L1 TPS<1%)
Intervention: Carboplatin (Drug)
IBI351 in combination with pemetrexed and cis-platinum/carboplatin (the subject with PD-L1 TPS<1%)
Intervention: cis-platinum (Drug)
IBI351 in combination with Cetuximab
Intervention: IBI351 (Drug)
IBI351 in combination with Cetuximab
Intervention: Cetuximab (Drug)
IBI351 monotherapy
Intervention: IBI351 (Drug)
IBI351 in combination with Sintilimab
Intervention: IBI351 (Drug)
IBI351 in combination with Sintilimab
Intervention: Sintilimab (Drug)
IBI351 in combination with pemetrexed and cis-platinum/carboplatin(the subject with PD-L1 TPS 1-49%)
Intervention: IBI351 (Drug)
IBI351 in combination with pemetrexed and cis-platinum/carboplatin(the subject with PD-L1 TPS 1-49%)
Intervention: pemetrexed (Drug)
IBI351 in combination with pemetrexed and cis-platinum/carboplatin(the subject with PD-L1 TPS 1-49%)
Intervention: Carboplatin (Drug)
IBI351 in combination with pemetrexed and cis-platinum/carboplatin(the subject with PD-L1 TPS 1-49%)
Intervention: cis-platinum (Drug)
Outcomes
Primary Outcomes
Number of participants with dose limiting toxicity
Time Frame: 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
Time Frame: 24 months
Objective response rate per RECIST v1.1
Safety indicators during the introduction phase for IBI351 combination treatment :
Time Frame: 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 Outcomes
- Evaluate plasma peak concentration of IBI351(12 months)
- Evaluate terminal half-life (t1/2) of IBI351(12 months)
- Evaluate distribution of IBI351(12 months)
- Evaluate clinical efficacy of IBI351 in combination with other therapeutic agents with other index(24 months)
- Number of subjects with adverse events of interest(24 months)
- Evaluate area under the plasma concentration-time curve (AUC) of IBI351(12 months)
- Evaluate clearance of IBI351 from the plasma(12 months)
- Number of subjects with treatment-related adverse events(24 months)
- Number of subjects with serious adverse events(24 months)
- Number of subjects with treatment-emergent adverse events(24 months)
- Overall Survival(24 months)