Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)

Phase 1

Completed

• Conditions: Advanced Cancer; Metastatic Cancer; Malignant Neoplastic Disease
• Interventions: Drug: MRTX849; Drug: TNO155

• Registration Number: NCT04330664
• Lead Sponsor: Mirati Therapeutics Inc.

Brief Summary

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.

Detailed Description

This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2.

This study was terminated prior to phase 2 initiating. Only phase 1 of the study was conducted.

Study Timeline

• Study First Submitted: 2020-03-30
• Study First Submitted QC: 2020-03-30
• Study First Posted: 2020-04-01
• Study Start: 2020-04-07
• Primary Completion: 2022-07-29
• Study Completion: 2025-02-24
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 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
Phase 2	TNO155	Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination
Phase 1 Dose Exploration	MRTX849	Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849
Phase 1 Dose Exploration	TNO155	Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849
Phase 1b Expansion	MRTX849	Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens
Phase 1b Expansion	TNO155	Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens
Phase 2	MRTX849	Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination

Primary Outcome Measures

Name	Time	Method
Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.	20 months	Number of participants with treatment related adverse events
Evaluate the pharmacokinetics of MRTX849 and TNO155	20 months	Blood plasma concentration

Secondary Outcome Measures

Name	Time	Method
Establish maximum tolerated dose	12 months	Number of participants with dose limiting toxicity
Evaluate clinical activity of MRTX849	20 months	Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Trial Locations

Locations (17)

Local Institution - 002-803; 🇺🇸 Orange, California, United States

Local Institution - 002-942; 🇺🇸 Wichita, Kansas, United States

Local Institution - 002-809; 🇺🇸 Saint Louis, Missouri, United States

Local Institution - 002-813; 🇺🇸 New York, New York, United States

Local Institution - 002-806; 🇺🇸 New York, New York, United States

Local Institution - 002-810; 🇺🇸 Milwaukee, Wisconsin, United States

Local Institution - 002-805; 🇺🇸 Los Angeles, California, United States

Local Institution - 002-828; 🇺🇸 Chicago, Illinois, United States

Local Institution - 002-811; 🇺🇸 Novi, Michigan, United States

Local Institution - 002-804; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 002-808; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 002-801; 🇺🇸 San Antonio, Texas, United States

Local Institution - 002-809 B; 🇺🇸 Creve Coeur, Missouri, United States

Local Institution - 002-809 A; 🇺🇸 Saint Louis, Missouri, United States

Local Institution - 002-809 C; 🇺🇸 Saint Louis, Missouri, United States

Local Institution - 002-809 E; 🇺🇸 Saint Louis, Missouri, United States

Local Institution - 002-809 D; 🇺🇸 Saint Peters, Missouri, United States