Clinical Trials /

Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1

NCT03785249

Description:

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03785249

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1
  • Official Title: A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1

Clinical Trial IDs

  • ORG STUDY ID: 849-001
  • NCT ID: NCT03785249

Conditions

  • Advanced Cancer
  • Metastatic Cancer
  • Malignant Neoplastic Disease

Interventions

DrugSynonymsArms
MRTX849Phase 1 Dose Exploration
PembrolizumabPilot Phase 1b Combination with Pembrolizumab
CetuximabPilot Phase 1b Combination with Cetuximab
AfatinibPilot Phase 1b Combination with Afatinib

Purpose

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) 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 (adagrasib) in patients with advanced
      solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small
      molecule inhibitor of KRAS G12C.

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose ExplorationExperimentalDose escalation of MRTX849 to determine maximum tolerated dose
  • MRTX849
Phase 1b ExpansionExperimentalExpansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens
  • MRTX849
Phase 2ExperimentalSeparate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity of MRTX849
  • MRTX849
Pilot Phase 1b Combination with PembrolizumabExperimentalPhase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC
  • MRTX849
  • Pembrolizumab
Pilot Phase 1b Combination with CetuximabExperimentalPhase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC
  • MRTX849
  • Cetuximab
Pilot Phase 1b Combination with AfatinibExperimentalPhase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC
  • MRTX849
  • Afatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation

          -  Unresectable or metastatic disease

          -  Standard treatment is not available or patient declines

          -  Adequate organ function

        Exclusion Criteria:

          -  History of intestinal disease or major gastric surgery or inability to swallow oral
             medications

          -  Other active cancer
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 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:Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents
Time Frame:12 months
Safety Issue:
Description:Number of participants with dose limiting toxicity
Measure:Evaluate the pharmacokinetics of new MRTX849 oral formulations
Time Frame:6 months
Safety Issue:
Description:Blood plasma concentration
Measure:Evaluate the pharmacokinetics of MRTX849 administered with food
Time Frame:6 months
Safety Issue:
Description:Blood plasma concentration

Details

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

Trial Keywords

  • KRAS
  • NSCLC
  • Colorectal Cancer
  • Colon Cancer
  • Metastatic Cancer
  • Pancreatic Cancer
  • Adagrasib

Last Updated

July 14, 2021