Adagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)

Phase 1

Terminated

• Conditions: Malignant Neoplasm of Lung; Metastatic Cancer; Malignant Neoplasm of Colon; Advanced Cancer; Malignant Neoplastic Disease
• Interventions: Drug: MRTX849; Drug: BI 1701963

• Registration Number: NCT04975256
• Lead Sponsor: Mirati Therapeutics Inc.

Brief Summary

This study will evaluate safety, tolerability, drug levels, molecular effects and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors that have a KRAS G12C mutation.

Detailed Description

This study will evaluate safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and BI 1701963 is a SOS1 pan-KRAS inhibitor.

Study Timeline

• Study First Submitted: 2021-07-06
• Study First Submitted QC: 2021-07-14
• Study First Posted: 2021-07-23
• Study Start: 2021-07-28
• Primary Completion: 2022-11-02
• Study Completion: 2022-11-15
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2024-12-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 1b must be either Non-Small Cell Lung Cancer or Colorectal Cancer)
• Unresectable or metastatic disease
• No available treatment with curative intent
• Adequate organ function

Exclusion Criteria

• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
• Other active cancer
• Cardiac abnormalities

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation	MRTX849	Dose escalation of MRTX849 and BI 1701963 to determine maximum tolerated dose in combination
Dose escalation	BI 1701963	Dose escalation of MRTX849 and BI 1701963 to determine maximum tolerated dose in combination
Dose expansion	MRTX849	Expansion cohorts in NSCLC and CRC patients to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with BI 1701963
Dose expansion	BI 1701963	Expansion cohorts in NSCLC and CRC patients to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with BI 1701963

Primary Outcome Measures

Name	Time	Method
Characterize the number of patients with treatment emergent adverse events of the combination regimen in patients with advanced solid tumor malignancies with KRAS G12C mutation	20 months	Number of participants with treatment related adverse events
Establish Maximum Tolerated Dose	12 months	Number of patients with dose limiting toxicity
Evaluate Pharmacokinetics of the combination regimen	20 months	Blood plasma concentration

Secondary Outcome Measures

Name	Time	Method
Evaluate preliminary clinical activity of the combination regimen	20 months	Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Trial Locations

Locations (4)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

The Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Next Oncology; 🇺🇸 San Antonio, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States