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

Primary Purpose

Advanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MRTX849
TNO155
Sponsored by
Mirati Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Cancer focused on measuring KRAS G12C, Non-small cell lung cancer, Colorectal Cancer, Colon Cancer, Metastatic Cancer, Pancreatic Cancer, NSCLC, SHP2, Advanced Solid Tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCLA Jonsson Comprehensive Cancer Center
  • UC Irvine Health
  • Northwestern
  • Cancer Center of Kansas
  • Massachusetts General Hospital
  • Dana Farber
  • Henry Ford
  • Washington University School of Medicine Siteman Cancer Center
  • NYU Perlmutter Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • NEXT Oncology
  • Froedtert Hospital & Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase 1 Dose Exploration

Phase 1b Expansion

Phase 2

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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
Evaluate the pharmacokinetics of MRTX849 and TNO155
Blood plasma concentration

Secondary Outcome Measures

Establish maximum tolerated dose
Number of participants with dose limiting toxicity
Evaluate clinical activity of MRTX849
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Full Information

First Posted
March 30, 2020
Last Updated
September 8, 2023
Sponsor
Mirati Therapeutics Inc.
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT04330664
Brief Title
Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)
Official Title
A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 22, 2020 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirati Therapeutics Inc.
Collaborators
Novartis

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
86 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 Dose Exploration
Arm Type
Experimental
Arm Description
Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849
Arm Title
Phase 1b Expansion
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination
Intervention Type
Drug
Intervention Name(s)
MRTX849
Other Intervention Name(s)
adagrasib
Intervention Description
KRAS G12C Inhibitor
Intervention Type
Drug
Intervention Name(s)
TNO155
Intervention Description
SHP2 Inhibitor
Primary Outcome Measure Information:
Title
Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.
Description
Number of participants with treatment related adverse events
Time Frame
20 months
Title
Evaluate the pharmacokinetics of MRTX849 and TNO155
Description
Blood plasma concentration
Time Frame
20 months
Secondary Outcome Measure Information:
Title
Establish maximum tolerated dose
Description
Number of participants with dose limiting toxicity
Time Frame
12 months
Title
Evaluate clinical activity of MRTX849
Description
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
20 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elise Walsh, MD
Organizational Affiliation
Mirati Therapeutics Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Jonsson Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UC Irvine Health
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Northwestern
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Henry Ford
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Washington University School of Medicine Siteman Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
NYU Perlmutter Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
NEXT Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Froedtert Hospital & Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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