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NCT06625775PHASE1Recruiting

Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors

TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

Start Date

10/29/2024

Completion Date

11/1/2028

Summary

First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.

Detailed Description

This is an open-label, multi-center Phase 1a/1b study designed to evaluate the safety, tolerability, preliminary antitumor activity, and PK of BBO-10203 as a single agent and in combination with Trastuzumab, Fulvestrant +/- Ribociclib, or FOLFOX + Bevacizumab in patients with locally advanced unresectable or metastatic (ie, advanced) solid tumors. The study includes a dose escalation phase and an expansion phase.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive/HER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC) * Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 * Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only) * Stable brain metastases * Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC) * Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy * BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4/6i * BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted * BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required Exclusion Criteria: * Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR/MSI-H tumors * Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1/BRAF/RET/MET/EGFR exon20 insertion/NTRK/HER2) * Patients with untreated and/or non-stable brain metastases Other inclusion/exclusion criteria are specified in the protocol

Interventions

DRUG

BBO-10203

DRUG

Trastuzumab

DRUG

Fulvestrant

DRUG

Ribociclib

DRUG

FOLFOX

DRUG

Bevacizumab

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Conditions

Solid Tumor, AdultMetastatic Breast CancerAdvanced Breast CancerHER2 Mutation-Related TumorsHER2-positive Metastatic Breast CancerKRAS Mutant Metastatic Colorectal CancerMetastatic Lung CancerMetastatic Colorectal CancerAdvanced Lung CancerHR-positive, HER2-negative Advanced Breast CancerHER2-positive Advanced Breast Cancer

Locations

City of Hope Comprehensive Cancer Center

Duarte, California 91010

United States

University of California Los Angeles

Los Angeles, California 90095

United States

University of California San Diego Moores Cancer Center

San Diego, California 92093

United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California 94158

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Indiana University Simon Comprehensive Cancer Center

Indianapolis, Indiana 46202

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana-Farber Cancer Insitute

Boston, Massachusetts 02215

United States

St. Lukes Hospital of Kansas City

Kansas City, Missouri 64111

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Columbia University Irving Medical Center

New York, New York 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

SCRI at Mary Crowley

Dallas, Texas 75230

United States

University of Texas Southwestern Medical Center

Dallas, Texas 75390

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

University of Texas San Antonio (UTSA)

San Antonio, Texas 78229

United States

Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

Wisconsin Institute for Medical Research

Madison, Wisconsin 53792

United States

Scientia Clinical Research

Randwick, New South Wales 2031

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

FUTTURA Oncologia

Porto Alegre, Rio Grande do Sul 90470

Brazil

Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul 90610

Brazil

Clinica de Pesquisas e Centro de Estudos Em Oncologia Ginecologica e Mamaria Ltda

São Paulo, São Paulo 01317

Brazil

IEPE - Unimed Sorocaba

Sorocaba, São Paulo 18056

Brazil

Institut régional du Cancer de Montpellier - Val d'Aurelle

Montpellier, Occitanie 34298

France

Institut Curie - René-Huguenin Hospital

Saint-Cloud, Paris 92210

France

lnstitut de Cancérologie de l'Ouest - Site Saint-Herblain

Saint-Herblain, Pays de la Loire Region 44805

France

Institut Bergonie

Bordeaux, 33000

France

Centre Léon Bérard

Lyon, 69008

France

Institut Gustave Roussy

Villejuif, Île-de-France Region 94805

France

Hospital Universitario Vall d'Hebron

Barcelona, Catalonia 08035

Spain

Hospital Beata Maria Ana

Madrid, Madrid 28007

Spain

Hospital Quiron Madrid - NEXT Oncology

Pozuelo de Alarcón, Madrid 28223

Spain

IOB Institute of Oncology - Hospital Quironsalud Barcelona

Barcelona, 08023

Spain

START Barcelona - HM Nou Delfos Hospital

Barcelona, 08023

Spain

Hospital Universitari Arnau de Vilanova

Lleida, 25198

Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitari i Politècnic La Fe

Valencia, 46026

Spain