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

A Phase 1/1b Trial of MRTX849 in Combination With BI 1701963 in Patients With Advanced Solid Tumors With KRAS G12C Mutation

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer; Advanced Cancer; Malignant Neoplasm of Colon; Malignant Neoplasm of Lung; Malignant Neoplastic Disease
• Intervention / Treatment: Drug: MRTX849; Drug: BI 1701963

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; Dose escalation of MRTX849 and BI 1701963 to determine maximum tolerated dose in combination	Drug: MRTX849; KRAS G12C inhibitor; Other Names: KRAS G12C inhibitor; adagrasib; Drug: BI 1701963; SOS1 Inhibitor; Other Names: SOS1 Inhibitor
Experimental: Dose expansion; 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	Drug: MRTX849; KRAS G12C inhibitor; Other Names: KRAS G12C inhibitor; adagrasib; Drug: BI 1701963; SOS1 Inhibitor; Other Names: SOS1 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Number of participants with treatment related adverse events	20 months
Evaluate Pharmacokinetics of the combination regimen	Blood plasma concentration	20 months
Establish Maximum Tolerated Dose	Number of patients with dose limiting toxicity	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.
• Collaborators: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2021
• Primary Completion (Actual): November 2, 2022
• Study Completion (Actual): November 15, 2022

Study Registration Dates

• First Submitted: July 6, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: NSCLC; Non Small Cell Lung Cancer; Pancreatic Cancer; KRAS G12C; Metastatic Cancer; Colon Cancer; Advanced Solid Tumor; CRC; adagrasib; SOS1 Inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Neoplastic Processes; Colorectal Neoplasms; Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Antineoplastic Agents; Adagrasib
• Other Study ID Numbers: 849-014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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