BBO-11818 in Adult Subjects With KRAS Mutant Cancer

Официальное название

A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-11818 in Subjects With Advanced KRAS Mutant Cancers

Обзор

A first in human study to evaluate the safety and preliminary antitumor activity of BBO-11818, a pan-KRAS inhibitor, in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors.

Подробное описание

This is an open-label, multi-center, Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of BBO-11818, a pan-KRAS inhibitor, alone and in combination with pembrolizumab, pembrolizumab + cis/carboplatin + pemetrexed, cetuximab, cetuximab + mFOLFOX6, BBO-10203 + mFOLFOX6, BBO-10203 +cetuximab, mFOLFIRINOX, gemcitabine + nab-paclitaxel, or BBO-10203 in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. The study includes a dose escalation phase and a dose expansion phase.

Вмешательства

• Препарат BBO-11818
  Participants will receive assigned dose of BBO-11818 orally (PO)
• Препарат Pembrolizumab
  Patients will receive IV pembrolizumab
• Препарат Platinum chemotherapy (cisplatin or carboplatin)
  Patients will receive IV platinum chemotherapy (cisplatin or carboplatin)
• Препарат Pemetrexed
  Patients will receive IV pemetrexed
• Препарат Cetuximab
  Patients will receive IV cetuximab
• Препарат mFOLFOX6
  Patients may receive IV mFOLFOX6
• Препарат mFOLFOX6
  Patients will receive IV mFOLFOX6
• Препарат BBO-10203
  Participants will receive BBO-10203 orally (PO)
• Препарат mFOLFIRINOX
  Patients will receive IV mFOLFIRINOX
• Препарат Gemcitabine
  Patients will receive IV gemcitabine

Первичные конечные точки

• Incidence and severity of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) [Срок оценки: approximately 5 years]
• Determine recommended dose of BBO-11818 in combination with pembrolizumab ± cis/carboplatin + pemetrexed, cetuximab ± mFOLFOX6, BBO-10203 + mFOLFOX6, BBO-10203 + cetuximab, cetuximab, mFOLFIRINOX, gemcitabine + nab-paclitaxel, or BBO-10203 [Срок оценки: approximately 5 years]

Вторичные конечные точки (8)

• Objective response rate (ORR) per RECIST v1.1 and CNS RECIST [Срок оценки: approximately 5 years]
• Clinical benefit rate (CBR) per RECIST v1.1 [Срок оценки: approximately 5 years]
• Duration of Response (DOR) per RECIST v1.1 [Срок оценки: approximately 5 years]
• Progression-Free Survival (PFS) per RECIST v1.1 [Срок оценки: approximately 5 years]
• Overall Survival (OS) [Срок оценки: approximately 5 years]
• Pharmacokinetics of BBO-11818, BBO-10203, irinotecan, and its metabolites (SN-38 and SN-38-G): Maximum blood concentration (Cmax) [Срок оценки: approximately 5 years]
• Pharmacokinetics of BBO-11818, BBO-10203, irinotecan, and its metabolites (SN-38 and SN-38-G): Time to achieve maximum concentration (Tmax) [Срок оценки: approximately 5 years]
• Pharmacokinetics of BBO-11818, BBO-10203, irinotecan, and its metabolites (SN-38 and SN-38-G): Area under the concentration-time curve (AUC) [Срок оценки: approximately 5 years]

Критерии участия

Критерии включения

• Histologically documented locally advanced and unresectable or metastatic NSCLC, PDAC, CRC, or other solid tumor with KRAS G12A, G12C, G12D, G12S, or G12V mutation
• Measurable disease by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Life expectancy >24 weeks
• Adequate organ function

Критерии исключения

• Malignancy within the last 2 years as specified in the protocol
• Untreated 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

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 16 центров

• The Angeles Clinic and Research Institute - West Los Angeles Office — Los Angeles
• University of California Davis — Sacramento
• University of California San Diego Moores Cancer Center — San Diego
• University of California San Francisco Helen Diller Family Comprehensive Cancer Center — San Francisco
• Yale University — New Haven
• Moffitt Cancer Center — Tampa
• OSF Healthcare Cancer Institute — Peoria
• Massachusetts General Hospital — Boston
• … и ещё 8 центров

Австралия · 1 центр

• Peter MacCallum Cancer Centre — Melbourne

Публикации

• Stahlhut C, Maciag AE, Sullivan KA, Singh K, Gitego N, Zhang Z, Chan AH, Sharma AK, Alexander PA, Shu J, Yang Y, Rigby M, Ma R, Setoodeh S, Smith BP, Pei J, Rabara D, Larsen EK, Turner DM, Zhang C, Feng C, Feng S, Stice JP, Xu R, Lin K, Stephen AG, Lightstone FC, Ji C, Wang K, Simanshu DK, Nissley DV, Wallace E, Wang B, Sinkevicius KW, McCormick F, Beltran PJ. Discovery of BBO-11818, a Potent and PMID 41790032

Идентификаторы

NCT: NCT06917079 · TBBO11818-101 · KONQUER-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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