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

Advanced Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05504278
• Other study ID #: CIBI351A301
• Status: Recruiting
• Phase: Phase 1
• Start date: September 20, 2022
• Est. completion date: July 31, 2027

Study information

• Verified date: May 2023
• Source: Innovent Biologics (Suzhou) Co. Ltd.
• Contact: Xiaodong Sun
• Phone: 0512-69566088
• Email: xiaodong.sun[@]innoventbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: July 31, 2027
• Est. primary completion date: May 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Non-Small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• pemetrexed
500mg/m^2, Q3W, day1, i.v.
• cis-platinum
75mg/m^2, Q3W, day1, i.v.
• Sintilimab
200mg, Q3W, day1, i.v.
• IBI351
recommended dose, po
• carboplatin
AUC=5, Q3W, day1, i.v.

Locations

Country	Name	City	State
China	Jilin Province Cancer Hospital	Jilin	Changchun

Sponsors (1)

Lead Sponsor	Collaborator
Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose limiting toxicity	Number of participants with dose limiting toxicity in the dose escalation period	12 months
Primary	Evaluate clinical efficacy of IBI351 in combination with other therapeutic agents	Objective response rate per RECIST v1.1	24 months
Secondary	Evaluate plasma peak concentration of IBI351	Cmax	12 months
Secondary	Evaluate area under the plasma concentration-time curve (AUC) of IBI351	AUC	12 months
Secondary	Evaluate terminal half-life (t1/2) of IBI351	t1/2	12 months
Secondary	Evaluate clearance of IBI351 from the plasma	CL/F	12 months
Secondary	Evaluate distribution of IBI351	V/F	12 months
Secondary	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
Secondary	Number of subjects with adverse events of interest	AE	24 months
Secondary	Number of subjects with treatment-related adverse events	TRAE	24 months
Secondary	Number of subjects with serious adverse events	SAE	24 months
Secondary	Number of subjects with treatment-emergent adverse events	TEAE	24 months