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

Non Small Cell Lung Cancer Clinical Trial

— Argonaut  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05480865
• Other study ID #: NAV-1003
• Status: Recruiting
• Phase: Phase 1
• Start date: July 6, 2022
• Est. completion date: June 2025

Study information

• Verified date: January 2024
• Source: Navire Pharma Inc., a BridgeBio company
• Contact: Navire Clinical Operations
• Phone: 650-391-9740
• Email: NAV1003ct.gov[@]bridgebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 85
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic NSCLC
• Metastatic Solid Tumor
• Neoplasms
• Non Small Cell Lung Cancer
• Solid Tumor, Adult

Intervention

Drug:
• BBP-398
BBP-398 administered orally
• sotorasib
sotorasib administered orally

Locations

Country	Name	City	State
Australia	Cancer Research SA	Adelaide	South Australia
Australia	Southern Oncology Clinical Research Unit	Adelaide	South Australia
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	Orange Health Service	Orange
Australia	One Clinical Research	Perth	Western Australia
Australia	St John of God Subiaco Hospital	Subiaco	Western Australia
Denmark	Rigshospitalet	Copenhagen
France	Institute Bergonie	Bordeaux
France	Centre Georges François Leclerc	Dijon
France	CHU Grenobles Aples	Grenoble
France	Hopital Bichat-Claude Bernard	Paris
France	CHU de Rennes - Hôpital Pontchaillou	Rennes
Greece	St. Luke's Hospital S.A.	Thessaloníki
Italy	Spedali Civili - Brescia	Brescia
Italy	Careggi University Hospital	Florence	Largo Brambilla
Italy	Istituto Nazionale Tumori (INT) "Fondazione G. Pascale"	Napoli
Italy	U.O.C Oncoematologia AOU "Luigi Vanvitelli"	Napoli
Netherlands	Het Nederlands Kanker Instituut - Antoni van Leewenhoek Ziekenhuis	Amsterdam
Netherlands	Erasmus Medical Center	Rotterdam
Spain	Quiron Salud Barcelona	Barcelona
Spain	Vall d'Heborn University Hospital - VHIO	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Quiron Salud Madrid	Madrid
Spain	Virgen De La Victoria	Málaga
Spain	Hospital Universitario Virgen De La Macarena	Sevilla

Sponsors (2)

Lead Sponsor	Collaborator
Navire Pharma Inc., a BridgeBio company	Amgen

Countries where clinical trial is conducted

Australia,  Denmark,  France,  Greece,  Italy,  Netherlands,  Spain, 

Outcome

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