SHP2 Inhibitor BBP-398 in Combination With Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation (Argonaut)

Navire Pharma

Status and phase: Terminated; Phase 1

Conditions: Solid Tumor, Adult; Non Small Cell Lung Cancer; Metastatic NSCLC; Metastatic Solid Tumor

Treatments: Drug: BBP-398; Drug: sotorasib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05480865

NAV-1003

Details and patient eligibility

About

This is a Phase 1 study of BBP-398, a SHP2 inhibitor, in combination with sotorasib, a KRAS-G12C inhibitor (KRAS-G12Ci), in patients with a KRAS-G12C mutation.

The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion/Optimization.

Full description

The primary objectives for Phase 1a Dose Escalation are to evaluate safety and tolerability, and recommend a phase 1b dose (RP1bD) of the combination.

The primary objectives for Phase 1b Dose Expansion/Optimization are to evaluate safety and tolerability, and the antitumor activity (defined by the ORR assessed by the investigator according to RECIST v1.1) of BBP-398 when used in combination with sotorasib across two dose regimens in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS-G12C mutation and who are KRAS-G12Ci naïve, and recommend a phase 2 dose (RP2D) of the combination.

Enrollment: 28 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients must have histologically documented, locally advanced and unresectable, or metastatic solid tumor with documentation of a KRAS-G12C mutation within 2 years prior to screening.
• Patients must have measurable disease by RECIST v1.1.
• Patients must have a minimum life expectancy of >12 weeks after start of study treatment.
• Patients must have progression or disease recurrence on or after all available standard of care therapies.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Patients must have adequate organ function.

Key Exclusion Criteria:

• Patients that have participated in an interventional clinical study within the last 4 weeks.
• Patients that have received radiotherapy or proton therapy with a limited field of radiation for palliation within 1 week of the start of study treatment, OR radiation to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the start of study treatment.
• Patients with untreated and/or active CNS metastases.
• Patients that have a history of allogenic bone marrow transplant.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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28 participants in 5 patient groups

Dose Escalation: BBP-398 Level 1 and sotorasib

Experimental group

Description:

BBP-398 dose Level 1 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle

Treatment:

Drug: sotorasib

Drug: BBP-398

Dose Escalation: BBP-398 Level 2 and sotorasib

Experimental group

Description:

BBP-398 dose Level 2 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle

Treatment:

Drug: sotorasib

Drug: BBP-398

Dose Escalation: BBP-398 Level 3 and sotorasib

Experimental group

Description:

BBP-398 dose Level 3 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle

Treatment:

Drug: sotorasib

Drug: BBP-398

Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib

Experimental group

Description:

BBP-398 Dose Regimen 1 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle

Treatment:

Drug: sotorasib

Drug: BBP-398

Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib

Experimental group

Description:

BBP-398 Dose Regimen 2 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle

Treatment:

Drug: sotorasib

Drug: BBP-398