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

NCT ID: NCT04330664

Last Updated: 2025-04-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-07

Study Completion Date

2025-02-24

Brief Summary

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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

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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.

Conditions

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Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1 Dose Exploration

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

Group Type EXPERIMENTAL

MRTX849

Intervention Type DRUG

KRAS G12C Inhibitor

TNO155

Intervention Type DRUG

SHP2 Inhibitor

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

Group Type EXPERIMENTAL

MRTX849

Intervention Type DRUG

KRAS G12C Inhibitor

TNO155

Intervention Type DRUG

SHP2 Inhibitor

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

Group Type EXPERIMENTAL

MRTX849

Intervention Type DRUG

KRAS G12C Inhibitor

TNO155

Intervention Type DRUG

SHP2 Inhibitor

Interventions

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MRTX849

KRAS G12C Inhibitor

Intervention Type DRUG

TNO155

SHP2 Inhibitor

Intervention Type DRUG

Other Intervention Names

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adagrasib

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

Mirati Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 002-805

Los Angeles, California, United States

Site Status

Local Institution - 002-803

Orange, California, United States

Site Status

Local Institution - 002-828

Chicago, Illinois, United States

Site Status

Local Institution - 002-942

Wichita, Kansas, United States

Site Status

Local Institution - 002-804

Boston, Massachusetts, United States

Site Status

Local Institution - 002-808

Boston, Massachusetts, United States

Site Status

Local Institution - 002-811

Novi, Michigan, United States

Site Status

Local Institution - 002-809 D

City of Saint Peters, Missouri, United States

Site Status

Local Institution - 002-809 B

Creve Coeur, Missouri, United States

Site Status

Local Institution - 002-809 A

St Louis, Missouri, United States

Site Status

Local Institution - 002-809 C

St Louis, Missouri, United States

Site Status

Local Institution - 002-809

St Louis, Missouri, United States

Site Status

Local Institution - 002-809 E

St Louis, Missouri, United States

Site Status

Local Institution - 002-813

New York, New York, United States

Site Status

Local Institution - 002-806

New York, New York, United States

Site Status

Local Institution - 002-801

San Antonio, Texas, United States

Site Status

Local Institution - 002-810

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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CA239-0017

Identifier Type: OTHER

Identifier Source: secondary_id

849-002

Identifier Type: OTHER

Identifier Source: secondary_id

CA239-0017

Identifier Type: -

Identifier Source: org_study_id

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