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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer; Metastatic Solid Tumor; Solid Tumor, Adult; Metastatic NSCLC
• Intervention / Treatment: Drug: BBP-398; Drug: sotorasib

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Orange, Australia, NSW 2800
    • Orange Health Service
  • South Australia
    • Adelaide, South Australia, Australia, 5042
      • Southern Oncology Clinical Research Unit
    • Adelaide, South Australia, Australia, 5000
      • Cancer Research SA
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula & South Eastern Haematology and Oncology Group
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • One Clinical Research
    • Subiaco, Western Australia, Australia, 6008
      • St John of God Subiaco Hospital
• Denmark
  • Copenhagen, Denmark, DK-2100
    • Rigshospitalet
• France
  • Bordeaux, France, 33076
    • Institute Bergonie
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc
  • Grenoble, France, 38043 CEDEX9
    • CHU Grenobles Aples
  • Paris, France, 75018
    • Hopital Bichat-Claude Bernard
  • Rennes, France, 35000
    • CHU de Rennes - Hôpital Pontchaillou
• Greece
  • Thessaloníki, Greece, 55236
    • St. Luke's Hospital S.A.
• Italy
  • Brescia, Italy, 25123
    • Spedali Civili - Brescia
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori (INT) "Fondazione G. Pascale"
  • Napoli, Italy, 80131
    • U.O.C Oncoematologia AOU "Luigi Vanvitelli"
  • Largo Brambilla
    • Florence, Largo Brambilla, Italy, 50134
      • Careggi University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Het Nederlands Kanker Instituut - Antoni van Leewenhoek Ziekenhuis
  • Rotterdam, Netherlands, 3000 CA
    • Erasmus Medical Center
• Spain
  • Barcelona, Spain, 08023
    • Quiron Salud Barcelona
  • Barcelona, Spain, 08035
    • Vall d'Heborn University Hospital - VHIO
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28223
    • Quiron Salud Madrid
  • Málaga, Spain, 29010
    • Virgen De La Victoria
  • Sevilla, Spain
    • Hospital Universitario Virgen De La Macarena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: BBP-398 Level 1 and sotorasib; 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; BBP-398 administered orally; Drug: sotorasib; sotorasib administered orally
Experimental: Dose Escalation: BBP-398 Level 2 and sotorasib; 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; BBP-398 administered orally; Drug: sotorasib; sotorasib administered orally
Experimental: Dose Escalation: BBP-398 Level 3 and sotorasib; 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; BBP-398 administered orally; Drug: sotorasib; sotorasib administered orally
Experimental: Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib; 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; BBP-398 administered orally; Drug: sotorasib; sotorasib administered orally
Experimental: Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib; 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; BBP-398 administered orally; Drug: sotorasib; sotorasib administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR)	Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1	8 weeks
Duration of response	Defined by RECIST v1.1	8 weeks
Progression Free Survival (PFS)	Time from treatment start to progression of disease or death by any cause	8 weeks
Overall survival (OS)	Time from treatment start to death	8 weeks
Maximum Observed Plasma Concentration (Cmax) of BBP-398	Maximum plasma concentration of BBP-398 in combination with sotorasib	Cycle 2 Day 1
Time to Cmax (Tmax) of BBP-398	Amount of time to reach Cmax of BBP-398 in combination with sotorasib	Cycle 2 Day 1
Area under the plasma concentration-time curve (AUC) of BBP-398	Area under the plasma concentration versus time curve of BBP-398 in combination with sotorasib	Cycle 2 Day 1
Half-life (T1/2) of BBP-398	Terminal half-life of BBP-398 in combination with sotorasib	Cycle 2 Day 1
Observed Maximum Plasma Concentration (Cmax) of sotorasib	Maximum plasma concentration of sotorasib in combination with BBP-398	Cycle 2 Day 1
Time to Cmax (Tmax) of sotorasib	Amount of time to reach Cmax of sotorasib in combination with BBP-398	Cycle 2 Day 1
Area under the plasma concentration-time curve (AUC) over dosing interval of sotorasib	Area under the plasma concentration versus time curve of sotorasib in combination with BBP-398	Cycle 2 Day 1
Half-life (T1/2) of sotorasib	Terminal half-life of sotorasib in combination with BBP-398	Cycle 2 Day 1
Circulating and intratumoral target engagement biomarkers of BBP-398 activity in combination with sotorasib	Raw, normalized, and/or baseline adjusted analyte signal	24 months

Collaborators and Investigators

• Sponsor: Navire Pharma Inc., a BridgeBio company
• Collaborators: Amgen
• Investigators: Study Director: Lauren Wood, MD, Navire Pharma Inc., a BridgeBio company; Study Director: Susanna Wen, MsM, PhD, Navire Pharma Inc., a BridgeBio company

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2022
• Primary Completion (Actual): August 22, 2024
• Study Completion (Actual): August 22, 2024

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 27, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Estimated): December 12, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; SHP2; MAPK-pathway alterations; KRAS-G12C mutation
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Sotorasib
• Other Study ID Numbers: NAV-1003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes