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

January 24, 2024 updated by: Mirati Therapeutics Inc.

A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Phase 2
  • Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

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

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Jonsson Comprehensive Cancer Center
      • Orange, California, United States, 92868
        • UC Irvine Health
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Cancer Center of Kansas
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine Siteman Cancer Center
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU Perlmutter Cancer Center
    • Texas
      • San Antonio, Texas, United States, 78229
        • Next Oncology
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital & Medical College of Wisconsin

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

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

How is the study designed?

Design Details

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

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
Other Names:
  • adagrasib
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
Other Names:
  • adagrasib
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
Other Names:
  • adagrasib
Drug: TNO155
SHP2 Inhibitor

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Sponsor

Mirati Therapeutics Inc.

Collaborators

Novartis

Investigators

  • Study Director: Medical Director, MD, Mirati Therapeutics Inc.

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 Major Dates

Study Start (Actual)

April 22, 2020

Primary Completion (Estimated)

March 1, 2024

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

March 30, 2020

First Submitted That Met QC Criteria

March 30, 2020

First Posted (Actual)

April 1, 2020

Study Record Updates

Last Update Posted (Actual)

January 26, 2024

Last Update Submitted That Met QC Criteria

January 24, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 849-002

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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