Clinical Trials /

Phase 1/2 Study in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL 2

NCT04330664

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Study in Patients With Cancer Having a KRAS G12C Mutation 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

Clinical Trial IDs

  • ORG STUDY ID: 849-002
  • NCT ID: NCT04330664

Conditions

  • Advanced Cancer
  • Metastatic Cancer
  • Malignant Neoplastic Disease

Interventions

DrugSynonymsArms
MRTX849Phase 1 Dose Exploration
TNO155Phase 1 Dose Exploration

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose ExplorationExperimentalDose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849
  • MRTX849
  • TNO155
Phase 1b ExpansionExperimentalExpansion 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
  • MRTX849
  • TNO155
Phase 2ExperimentalSeparate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination
  • MRTX849
  • TNO155

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mirati Therapeutics Inc.

Trial Keywords

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

Last Updated

December 22, 2020