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

Study Overview

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

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.

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.

Advanced Cancer
Metastatic Cancer
Malignant Neoplasm of Colon
Malignant Neoplasm of Lung
Malignant Neoplastic Disease

DRUG: MRTX849
DRUG: BI 1701963

849-014

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-07-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-12-12
First Submitted that Met QC Criteria 2021-07-14	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-12-16
First Posted (ACTUAL) 2021-07-23	Results First Posted N/A	Last Verified 2024-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

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 DRUG: BI 1701963 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 DRUG: BI 1701963 SOS1 Inhibitor

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

DRUG: BI 1701963

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

DRUG: BI 1701963

SOS1 Inhibitor

Primary Outcome Measures	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	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Boehringer Ingelheim

Investigators

STUDY_DIRECTOR: Richard Chao, MD, Mirati Therapeutics

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

PatientS

Caregivers

Clinical Trial Record