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

Mirati Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Metastatic Cancer; Advanced Cancer; Malignant Neoplastic Disease

Treatments: Drug: Cetuximab; Drug: Afatinib; Drug: Pembrolizumab; Drug: MRTX849

Study type: Interventional

Funder types: Industry

Identifiers

NCT03785249

849-001

CA239-0008

Details and patient eligibility

About

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.

Full 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.

Enrollment: 822 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Exclusion criteria

• History of intestinal disease or major gastric surgery or inability to swallow oral medications
• Other active cancer

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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822 participants in 9 patient groups

Phase 1 Dose Exploration

Experimental group

Description:

Dose escalation of MRTX849 to determine maximum tolerated dose

Treatment:

Drug: MRTX849

Phase 1b Expansion

Experimental group

Description:

Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens

Treatment:

Drug: MRTX849

Phase 2

Experimental group

Description:

Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849

Treatment:

Drug: MRTX849

Pilot Phase 1b Combination with Pembrolizumab

Experimental group

Description:

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC

Treatment:

Drug: MRTX849

Drug: Pembrolizumab

Pilot Phase 1b Combination with Cetuximab

Experimental group

Description:

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC

Treatment:

Drug: MRTX849

Drug: Cetuximab

Pilot Phase 1b Combination with Afatinib

Experimental group

Description:

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC

Treatment:

Drug: MRTX849

Drug: Afatinib

Phase 2 Combination with Cetuximab

Experimental group

Description:

Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC

Treatment:

Drug: MRTX849

Drug: Cetuximab

Pilot Phase 1b Combination with Cetuximab in NSCLC

Experimental group

Description:

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC

Treatment:

Drug: MRTX849

Drug: Cetuximab

Pilot Phase 1b Combination with Cetuximab in PDAC

Experimental group

Description:

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)

Treatment:

Drug: MRTX849

Drug: Cetuximab