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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: pemetrexed; Drug: Sintilimab; Drug: IBI351; Drug: cis-platinum; Drug: carboplatin

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 Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiaodong Sun; Phone Number: 0512-69566088; Email: xiaodong.sun@innoventbio.com

Study Locations

• China
  • Changchun
    • Jilin, Changchun, China
      • Recruiting
      • Jilin Province Cancer Hospital
      • Contact: Ying Cheng; Phone Number: 0431-80596315; Email: jl.cheng@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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: Sintilimab; 200mg, Q3W, day1, i.v.; Other Names: IBI308; Drug: IBI351; recommended dose, po; Other Names: GFH925; Drug: cis-platinum; 75mg/m^2, Q3W, day1, i.v.; Drug: carboplatin; AUC=5, Q3W, day1, i.v.
Experimental: IBI351 monotherapy	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with dose limiting toxicity	Number of participants with dose limiting toxicity in the dose escalation period	12 months
Evaluate clinical efficacy of IBI351 in combination with other therapeutic agents	Objective response rate per RECIST v1.1	24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2022
• Primary Completion (Estimated): May 12, 2024
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: August 11, 2022
• First Submitted That Met QC Criteria: August 15, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Carboplatin; Cisplatin; Pemetrexed
• Other Study ID Numbers: CIBI351A301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No