Adagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)

Mirati Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Metastatic Cancer; Advanced Cancer; Malignant Neoplastic Disease; Malignant Neoplasm of Lung; Malignant Neoplasm of Colon

Treatments: Drug: BI 1701963; Drug: MRTX849

Study type: Interventional

Funder types: Industry

Identifiers

NCT04975256

849-014

Details and patient eligibility

About

This study will evaluate safety, tolerability, drug levels, molecular effects and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors that have a KRAS G12C mutation.

Full description

This study will evaluate safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and BI 1701963 is a SOS1 pan-KRAS inhibitor.

Enrollment: 7 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 (phase 1b 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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7 participants in 2 patient groups

Dose escalation

Experimental group

Description:

Dose escalation of MRTX849 and BI 1701963 to determine maximum tolerated dose in combination

Treatment:

Drug: MRTX849

Drug: BI 1701963

Dose expansion

Experimental group

Description:

Expansion cohorts in NSCLC and CRC patients to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with BI 1701963

Treatment:

Drug: MRTX849

Drug: BI 1701963