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

Study Overview

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

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.

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.

Advanced Cancer
Metastatic Cancer
Malignant Neoplastic Disease

DRUG: MRTX849
DRUG: TNO155

CA239-0017
CA239-0017 (OTHER Identifier) (OTHER: Bristol-Myers Squibb Protocol ID)
849-002 (OTHER Identifier) (OTHER: Mirati Therapeutics Protocol ID)

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 2020-03-30	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-03
First Submitted that Met QC Criteria 2020-03-30	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-04
First Posted (ACTUAL) 2020-04-01	Results First Posted N/A	Last Verified 2025-03

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: Phase 1 Dose Exploration Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849	DRUG: MRTX849 KRAS G12C Inhibitor DRUG: TNO155 SHP2 Inhibitor
EXPERIMENTAL: Phase 1b Expansion 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	DRUG: MRTX849 KRAS G12C Inhibitor DRUG: TNO155 SHP2 Inhibitor
EXPERIMENTAL: Phase 2 Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination	DRUG: MRTX849 KRAS G12C Inhibitor DRUG: TNO155 SHP2 Inhibitor

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Phase 1 Dose Exploration

Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849

DRUG: MRTX849

KRAS G12C Inhibitor

DRUG: TNO155

SHP2 Inhibitor

EXPERIMENTAL: Phase 1b Expansion

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

DRUG: MRTX849

KRAS G12C Inhibitor

DRUG: TNO155

SHP2 Inhibitor

EXPERIMENTAL: Phase 2

Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination

DRUG: MRTX849

KRAS G12C Inhibitor

DRUG: TNO155

SHP2 Inhibitor

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

Secondary Outcome Measures	Measure Description	Time Frame
Establish maximum tolerated dose	Number of participants with dose limiting toxicity	12 months
Evaluate clinical activity of MRTX849	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 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

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.

Novartis

Investigators

STUDY_DIRECTOR: Bristol-Myers Squibb, Bristol-Myers Squibb

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