Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)

Mirati Therapeutics

Status and phase: Active, not recruiting; Phase 1

Conditions: Metastatic Cancer; Advanced Cancer; Malignant Neoplastic Disease

Treatments: Drug: TNO155; Drug: MRTX849

Study type: Interventional

Funder types: Industry

Identifiers

NCT04330664

849-002

CA239-0017

Details and patient eligibility

About

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.

Full 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.

This study was terminated prior to phase 2 initiating. Only phase 1 of the study was conducted.

Enrollment: 86 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 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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86 participants in 3 patient groups

Phase 1 Dose Exploration

Experimental group

Description:

Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849

Treatment:

Drug: TNO155

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 in combination with TNO155 to recommend Phase 2 regimens

Treatment:

Drug: TNO155

Drug: MRTX849

Phase 2

Experimental group

Description:

Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination

Treatment:

Drug: TNO155

Drug: MRTX849