Title
A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients with Advanced Solid Tumors with KRAS G12C Mutation

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.

Objective
Primary Outcome Measures:

Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation [ Time Frame: 20 months ]


Number of participants with treatment related adverse events


Evaluate the pharmacokinetics of MRTX849 [ Time Frame: 20 months ]


Blood plasma concentration


Evaluate clinical activity/efficacy of MRTX849 [ Time Frame: 20 months ]


Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Establish maximum tolerated dose [ Time Frame: 12 months ]


Number of participants with dose limiting toxicity


Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents [ Time Frame: 12 months ]


Number of participants with dose limiting toxicity


Evaluate the pharmacokinetics of new MRTX849 oral formulations [ Time Frame: 6 months ]


Blood plasma concentration


Evaluate the pharmacokinetics of MRTX849 administered with food [ Time Frame: 6 months ]


Blood plasma concentration

Treatment Study 849-001 is a multi-center, Phase 1/2, multiple expansion cohort trial evaluating the safety, PK, metabolites, PD and clinical activity/efficacy of MRTX849 in patients with advanced solid tumor malignancies with KRAS G12C mutation. This protocol is designed as recommended in United States Food and Drug Administration (US FDA) draft guidance for conduct of first-in-human multiple expansion cohort trials (FDA-2018). Oversight for this clinical trial is provided by the Sponsor, Investigators, local Institutional Review Boards (IRBs), a specifically commissioned Central IRB and an Independent Data Monitoring Committee (IDMC).

Key Eligibility 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; first-line treatment for NSCLC for certain cohorts

Adequate organ function

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

Other active cancer

Applicable Disease Sites
Colon and Rectum; Lung

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital