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

NCT05480865 | Terminated Phase 1 FDA Drug

• 1 other identifier: NAV-1003
• Study Type: interventional
• Target: 28
• Locations: 7 countries
• Sites: 25

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.

Conditions

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

Keywords

KRAS-G12C mutation; SHP2; MAPK-pathway alterations; NSCLC

Outcome Measures

Primary Outcomes (3)

• Phase 1a Dose Escalation Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, Serious Adverse Events, and Dose Limiting Toxicities

  Number of patients experiencing treatment-emergent adverse events, serious adverse events, including changes in lab parameters, vital signs and electrocardiogram changes; duration, and severity based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  Completion of 1 Cycle (28 days)

• Phase 1b Dose Expansion/Optimization Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, and Serious Adverse Events

  Number of patients experiencing treatment-emergent adverse events, serious adverse events, including changes in lab parameters, vital signs and electrocardiogram changes; duration, and severity based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  Completion of 1 Cycle (28 days)

• Phase 1b Dose Expansion/Optimization Primary Objective: Overall Response Rate (ORR)

  Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1

  8 weeks

Secondary Outcomes (13)

• Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR)

  8 weeks

• Duration of response

  8 weeks

• Progression Free Survival (PFS)

  8 weeks

• Overall survival (OS)

  8 weeks

• Maximum Observed Plasma Concentration (Cmax) of BBP-398

  Cycle 2 Day 1

Study Arms (5)

Dose Escalation: BBP-398 Level 1 and sotorasib

EXPERIMENTAL

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

Drug: BBP-398; Drug: sotorasib

Dose Escalation: BBP-398 Level 2 and sotorasib

EXPERIMENTAL

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

Drug: BBP-398; Drug: sotorasib

Dose Escalation: BBP-398 Level 3 and sotorasib

EXPERIMENTAL

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

Drug: BBP-398; Drug: sotorasib

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

EXPERIMENTAL

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

Drug: BBP-398; Drug: sotorasib

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

EXPERIMENTAL

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

Drug: BBP-398; Drug: sotorasib

Interventions

BBP-398 DRUG

BBP-398 administered orally

Dose Escalation: BBP-398 Level 1 and sotorasib; Dose Escalation: BBP-398 Level 2 and sotorasib; Dose Escalation: BBP-398 Level 3 and sotorasib; Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib; Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib

sotorasib DRUG

sotorasib administered orally

Dose Escalation: BBP-398 Level 1 and sotorasib; Dose Escalation: BBP-398 Level 2 and sotorasib; Dose Escalation: BBP-398 Level 3 and sotorasib; Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib; Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Navire Pharma Inc., a BridgeBio company: lead
• Amgen: collaborator

Study Sites (25)

Cancer Research SA

Adelaide, South Australia, 5000, Australia

Location

Southern Oncology Clinical Research Unit

Adelaide, South Australia, 5042, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

One Clinical Research

Perth, Western Australia, 6009, Australia

Location

St John of God Subiaco Hospital

Subiaco, Western Australia, 6008, Australia

Location

Orange Health Service

Orange, NSW 2800, Australia

Location

Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Institute Bergonie

Bordeaux, 33076, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

CHU Grenobles Aples

Grenoble, 38043 CEDEX9, France

Location

Hopital Bichat-Claude Bernard

Paris, 75018, France

Location

CHU de Rennes - Hôpital Pontchaillou

Rennes, 35000, France

Location

St. Luke's Hospital S.A.

Thessaloniki, 55236, Greece

Location

Careggi University Hospital

Florence, Largo Brambilla, 50134, Italy

Location

Spedali Civili - Brescia

Brescia, 25123, Italy

Location

Istituto Nazionale Tumori (INT) "Fondazione G. Pascale"

Napoli, 80131, Italy

Location

U.O.C Oncoematologia AOU "Luigi Vanvitelli"

Napoli, 80131, Italy

Location

Het Nederlands Kanker Instituut - Antoni van Leewenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3000 CA, Netherlands

Location

Quiron Salud Barcelona

Barcelona, 08023, Spain

Location

Vall d'Heborn University Hospital - VHIO

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Quiron Salud Madrid

Madrid, 28223, Spain

Location

Virgen De La Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Virgen De La Macarena

Seville, Spain

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung

Interventions

sotorasib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: July 29, 2022
• Study Start: July 6, 2022
• Primary Completion: August 22, 2024
• Study Completion: August 22, 2024
• Last Updated: December 12, 2024

Record last verified: 2024-12

Locations

FR (5); DK (1); GR (1); AU (6); IT (4); ES (6); NL (2)