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

NCT04330664 | Completed Phase 1 FDA Drug

• 2 other identifiers: CA239-0017849-002
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Advanced Cancer; Metastatic Cancer; Malignant Neoplastic Disease

Keywords

KRAS G12C; Non-small cell lung cancer; Colorectal Cancer; Colon Cancer; Metastatic Cancer; Pancreatic Cancer; NSCLC; SHP2; Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Establish maximum tolerated dose

  12 months

• Evaluate clinical activity of MRTX849

  20 months

Study Arms (3)

Phase 1 Dose Exploration

EXPERIMENTAL

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

Drug: MRTX849; Drug: TNO155

Phase 1b Expansion

EXPERIMENTAL

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; Drug: TNO155

Phase 2

EXPERIMENTAL

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; Drug: TNO155

Interventions

MRTX849 DRUG

KRAS G12C Inhibitor

Also known as: adagrasib

Phase 1 Dose Exploration; Phase 1b Expansion; Phase 2

TNO155 DRUG

SHP2 Inhibitor

Phase 1 Dose Exploration; Phase 1b Expansion; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead
• Novartis: collaborator

Study Sites (17)

Local Institution - 002-805

Los Angeles, California, 90095, United States

Location

Local Institution - 002-803

Orange, California, 92868, United States

Location

Local Institution - 002-828

Chicago, Illinois, 60611, United States

Location

Local Institution - 002-942

Wichita, Kansas, 67214, United States

Location

Local Institution - 002-804

Boston, Massachusetts, 02114, United States

Location

Local Institution - 002-808

Boston, Massachusetts, 02215, United States

Location

Local Institution - 002-811

Novi, Michigan, 48377, United States

Location

Local Institution - 002-809 D

City of Saint Peters, Missouri, 63376, United States

Location

Local Institution - 002-809 B

Creve Coeur, Missouri, 63141, United States

Location

Local Institution - 002-809 A

St Louis, Missouri, 63110, United States

Location

Local Institution - 002-809 C

St Louis, Missouri, 63129, United States

Location

Local Institution - 002-809

St Louis, Missouri, 63130, United States

Location

Local Institution - 002-809 E

St Louis, Missouri, 63136, United States

Location

Local Institution - 002-813

New York, New York, 10016, United States

Location

Local Institution - 002-806

New York, New York, 10065, United States

Location

Local Institution - 002-801

San Antonio, Texas, 78229, United States

Location

Local Institution - 002-810

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Colonic Neoplasms; Pancreatic Neoplasms

Interventions

adagrasib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 1, 2020
• Study Start: April 7, 2020
• Primary Completion: July 29, 2022
• Study Completion: February 24, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)