SHP2 Inhibitor BBP-398 in Combination With Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation

Navire Pharma

Status and phase: Terminated; Phase 1

Conditions: Solid Tumor; Non Small Cell Lung Cancer

Treatments: Drug: BBP-398 with nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05375084

NAV-1004

Details and patient eligibility

About

This is a Phase 1 study of BBP-398, a SHP2 inhibitor, in combination with nivolumab, a PD-1 antibody, in patients with NSCLC with a KRAS mutation. The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion.

Full description

The primary objective for Phase 1a Dose Escalation is to evaluate the safety, tolerability, and RP2D of BBP-398, a SHP2 inhibitor, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.

The primary objective for Phase 1b Dose Expansion is to evaluate the antitumor activity of BBP-398, as defined by the ORR (per investigator) according to RECIST v1.1, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients must have histologically documented, locally advanced and unresectable, or metastatic NSCLC with documentation of a KRAS mutation within the 1 year 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 at least one prior line of systemic therapy, which must include platinum-based doublet chemotherapy and anti-PD-(L)1 therapy.
• Patients must have experienced progressive or recurrent disease occurring either during treatment or within 90 days after discontinuing anti-PD-(L)1 therapy.
• 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 known central nervous system (CNS) tumors or active CNS metastases.
• Patients that have experienced progressive disease (PD) within the first 120 days of initiating treatment with an anti- PD-(L)1 agent (e.g., primary refractory).
• Patients that have a history of allogenic bone marrow transplant.
• Patients that have select known or suspected autoimmune disease.
• Patients that have a condition requiring systemic treatment with either corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive medication within 14 days of study start.
• Patients that have received any live/attenuated vaccine within 30 days of first study treatment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 4 patient groups

Dose Escalation Level 1

Experimental group

Description:

Level 1 oral capsules administered in combination with nivolumab

Treatment:

Drug: BBP-398 with nivolumab

Dose Escalation Level 2

Experimental group

Description:

Level 2 oral capsules administered in combination with nivolumab

Treatment:

Drug: BBP-398 with nivolumab

Dose Escalation Level 3

Experimental group

Description:

Level 3 oral capsules administered in combination with nivolumab

Treatment:

Drug: BBP-398 with nivolumab

Dose Expansion

Experimental group

Description:

RP2D defined dose. Oral capsules administered in combination with nivolumab

Treatment:

Drug: BBP-398 with nivolumab