PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates

Mirati Therapeutics

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Digoxin; Drug: Dextromethorphan; Drug: Nivolumab; Drug: Rosuvastatin; Drug: Warfarin; Drug: Sitravatinib; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT04887194

516-010

Details and patient eligibility

About

Study 516-010 is an open-label Phase 1, drug-drug interaction and QTc study evaluating the effect of sitravatinib on probe substrates for CYP450 enzymes and BCRP and P-gp transporters.

Full description

Part 1 of this study is designed to evaluate the potential for drug-drug interactions and QTc effects with sitravatinib monotherapy when administered with probe drugs for specific cytochrome P450 (CYP) enzymes (CYP2C9, CYP2D6, and CYP3A4) and P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters

Part 2 allows for patients to continue sitravatinib treatment with the addition of the checkpoint inhibitor Nivolumab.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed diagnosis of unresectable advanced/metastatic solid tumor
• Life expectancy of at least 3 months
• Adequate bone marrow and organ function

Exclusion criteria

• Ongoing medical condition or need for treatment with medication that may affect the PK of study treatments during Part 1
• Immunocompromising conditions
• Impaired heart function
• Active or prior documented autoimmune disease

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 3 patient groups

Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)

Experimental group

Description:

To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).

Treatment:

Drug: Midazolam

Drug: Sitravatinib

Drug: Warfarin

Drug: Rosuvastatin

Drug: Digoxin

Drug: Dextromethorphan

Phase 1, Part 1: Sitravatinib monotherapy (QTc cohort)

Experimental group

Description:

To evaluate the QTc prolongation risk for sitravatinib in patients with advanced/metastatic solid tumors via C-QTc modeling.

Treatment:

Drug: Sitravatinib

Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts)

Experimental group

Description:

To evaluate safety and tolerability of Sitravatinib treatment with the addition of the checkpoint inhibitor nivolumab.

Treatment:

Drug: Sitravatinib

Drug: Nivolumab