Clinical trial NCT05375084: SHP2 Inhibitor BBP-398 in Combination With Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation
Official title: A Phase 1 Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Combination With the Programmed Death Receptor-1 Blocking Antibody Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Solid Tumor
Keywords: KRAS mutation
MAPK-pathway alterations
NSCLC
SHP2
Lead sponsor: Navire Pharma Inc., a BridgeBio company
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2022-05-16
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Phase 1a Dose Escalation: Assess safety, tolerability, and recommended phase 2 dose (RP2D) of BBP-398 in combination with nivolumab
timeFrame: Completion of 1 Cycle (28 days)
measure: Phase 1b Dose Expansion: Assess antitumor activity of BBP-398 in combination with nivolumab
timeFrame: Completion of 1 Cycle (28 days)
Secondary outcomes:
measure: Assess preliminary antitumor activity of BBP-398 in combination with nivolumab
timeFrame: Completion of 1 Cycle (28 days)
measure: Phase 1b Dose Expansion: Assess safety and tolerability of BBP-398 at the RP2D, in combination with nivolumab
timeFrame: Completion of 1 Cycle (28 days)
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology
state: Arkansas
city: La Jolla
country: United States
facility: Scripps Clinic Torrey Pines
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation
state: California
city: Hollywood
country: United States
facility: Memorial Regional Hospital (Memorial Cancer Institute)
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania (Abramson Cancer Center)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) - Hollings Cancer Center
state: South Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Millennium Research and Clinical Development
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
Study officials:
References: