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

Официальное название

A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects With Advanced Solid Tumors (The BREAKER-101 Study)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат BBO-10203
  Participants will receive assigned dose of BBO-10203 orally once daily
• Препарат Trastuzumab
  Participants will receive trastuzumab as infusion or subcutaneous injection every 21 days
• Препарат Fulvestrant
  Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15)
• Препарат Ribociclib
  Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off)
• Препарат FOLFOX
  Patients will receive FOLFOX as infusion every 14 days
• Препарат Bevacizumab
  Patients will receive bevacizumab as infusion every 28 days

Первичные конечные точки

• Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BBO-10203 as a single agent [Срок оценки: Up to approximately 5 years]
• Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) [Срок оценки: Up to approximately 5 years]
• Recommended BBO-10203 dose in combination with trastuzumab, fulvestrant +/- ribociclib, and FOLFOX + bevacizumab [Срок оценки: Up to approximately 5 years]

Вторичные конечные точки (8)

• Clinical benefit rate (CBR) as assessed by RECIST v1.1. [Срок оценки: Up to approximately 5 years]
• Duration of response (DOR) as assessed by RECIST v1.1. [Срок оценки: Up to approximately 5 years]
• Progression-free survival (PFS) as assessed by RECIST v1.1 [Срок оценки: Up to approximately 5 years]
• Overall survival (OS) [Срок оценки: Up to approximately 5 years]
• Area under the concentration-time curve (AUC [Срок оценки: Predose (within 30 minutes) of C1D1 until up to approximately 5 years]
• Maximum plasma drug concentration (Cmax) [Срок оценки: Predose (within 30 minutes) of C1D1 until up to approximately 5 years]
• Time for maximum plasma drug concentration (Tmax) [Срок оценки: Predose (within 30 minutes) of C1D1 until up to approximately 5 years]
• Objective response rate (ORR) as assessed by RECIST v1.1 for patients with measurable disease [Срок оценки: Up to approximately 5 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 19 центров

• City of Hope Comprehensive Cancer Center — Duarte
• University of California Los Angeles — Los Angeles
• University of California San Diego Moores Cancer Center — San Diego
• UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco
• Moffitt Cancer Center — Tampa
• Indiana University Simon Comprehensive Cancer Center — Indianapolis
• Massachusetts General Hospital — Boston
• Dana-Farber Cancer Insitute — Boston
• … и ещё 11 центров

Испания · 9 центров

• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Beata Maria Ana — Madrid
• Hospital Quiron Madrid - NEXT Oncology — Pozuelo de Alarcón
• IOB Institute of Oncology - Hospital Quironsalud Barcelona — Barcelona
• START Barcelona - HM Nou Delfos Hospital — Barcelona
• Hospital Universitari Arnau de Vilanova — Lleida
• Hospital Universitario Fundación Jiménez Díaz — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• … и ещё 1 центр

Франция · 6 центров

• Institut régional du Cancer de Montpellier - Val d'Aurelle — Montpellier
• Institut Curie - René-Huguenin Hospital — Saint-Cloud
• lnstitut de Cancérologie de l'Ouest - Site Saint-Herblain — Saint-Herblain
• Institut Bergonie — Bordeaux
• Centre Léon Bérard — Lyon
• Institut Gustave Roussy — Villejuif

Бразилия · 4 центра

• FUTTURA Oncologia — Porto Alegre
• Hospital São Lucas da PUCRS — Porto Alegre
• Clinica de Pesquisas e Centro de Estudos Em Oncologia Ginecologica e Mamaria Ltda — São Paulo
• IEPE - Unimed Sorocaba — Sorocaba

Австралия · 2 центра

• Scientia Clinical Research — Randwick
• Peter MacCallum Cancer Centre — Melbourne

Идентификаторы

NCT: NCT06625775 · TBBO10203-101 · 2024-519445-29-00 · BREAKER-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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