Clinical trial NCT05480865: SHP2 Inhibitor BBP-398 in Combination With Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation
Official title: A Phase 1 Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Combination With the KRAS-G12C Inhibitor Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor, Adult
Metastatic Solid Tumor
Metastatic NSCLC
Non Small Cell Lung Cancer
Keywords: KRAS-G12C mutation
SHP2
MAPK-pathway alterations
NSCLC
Lead sponsor: Navire Pharma Inc., a BridgeBio company
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2022-07-29
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Phase 1a Dose Escalation Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, Serious Adverse Events, and Dose Limiting Toxicities
timeFrame: Completion of 1 Cycle (28 days)
measure: Phase 1b Dose Expansion/Optimization Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, and Serious Adverse Events
timeFrame: Completion of 1 Cycle (28 days)
measure: Phase 1b Dose Expansion/Optimization Primary Objective: Overall Response Rate (ORR)
timeFrame: 8 weeks
Secondary outcomes:
measure: Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR)
timeFrame: 8 weeks
measure: Duration of response
timeFrame: 8 weeks
measure: Progression Free Survival (PFS)
timeFrame: 8 weeks
measure: Overall survival (OS)
timeFrame: 8 weeks
measure: Maximum Observed Plasma Concentration (Cmax) of BBP-398
timeFrame: Cycle 2 Day 1
measure: Time to Cmax (Tmax) of BBP-398
timeFrame: Cycle 2 Day 1
measure: Area under the plasma concentration-time curve (AUC) of BBP-398
timeFrame: Cycle 2 Day 1
measure: Half-life (T1/2) of BBP-398
timeFrame: Cycle 2 Day 1
measure: Observed Maximum Plasma Concentration (Cmax) of sotorasib
timeFrame: Cycle 2 Day 1
measure: Time to Cmax (Tmax) of sotorasib
timeFrame: Cycle 2 Day 1
measure: Area under the plasma concentration-time curve (AUC) over dosing interval of sotorasib
timeFrame: Cycle 2 Day 1
measure: Half-life (T1/2) of sotorasib
timeFrame: Cycle 2 Day 1
measure: Circulating and intratumoral target engagement biomarkers of BBP-398 activity in combination with sotorasib
timeFrame: 24 months
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Cancer Research SA
state: South Australia
city: Adelaide
country: Australia
facility: Southern Oncology Clinical Research Unit
state: South Australia
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
city: Perth
country: Australia
facility: One Clinical Research
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
city: Orange
country: Australia
facility: Orange Health Service
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Bordeaux
country: France
facility: Institute Bergonie
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Grenoble
country: France
facility: CHU Grenobles Aples
city: Paris
country: France
facility: Hopital Bichat-Claude Bernard
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Thessaloníki
country: Greece
facility: St. Luke's Hospital S.A.
city: Florence
country: Italy
facility: Careggi University Hospital
state: Largo Brambilla
city: Brescia
country: Italy
facility: Spedali Civili - Brescia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori (INT) "Fondazione G. Pascale"
city: Napoli
country: Italy
facility: U.O.C Oncoematologia AOU "Luigi Vanvitelli"
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut - Antoni van Leewenhoek Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Barcelona
country: Spain
facility: Quiron Salud Barcelona
city: Barcelona
country: Spain
facility: Vall d'Heborn University Hospital - VHIO
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Quiron Salud Madrid
city: Málaga
country: Spain
facility: Virgen De La Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen De La Macarena
Study officials:
References: