BBO-11818 in Adult Subjects With KRAS Mutant Cancer

Conditions

Non-Small Cell Lung Cancer, NSCLC, PDAC - Pancreatic Ductal Adenocarcinoma, CRC (Colorectal Cancer), Metastatic Non-Small Lung Cell Cancer, Metastatic Colorectal Cancer (CRC), KRAS G12A, KRAS G12C, KRAS G12D, KRAS G12S, KRAS G12V, Metastatic Pancreatic Ductal Adenocarcinoma, Advanced Lung Carcinoma, Solid Tumor, Adult

Keywords

BBOT, BridgeBio Oncology Therapeutics, Phase1, Phase 1a/1b, NSCLC, CRC, PDAC, Metastatic Cancer, Advanced Cancer, Pembrolizumab, Cetuximab, Platinum Chemotherapy, Pemetrexed, KONQUER, KONQUER-101, FOLFOX, NALIRIFOX, Gemcitabine, Nab-paclitaxel

Brief summary

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.

Detailed description

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 +/- FOLFOX, NALIRIFOX, or Gemcitabine + Nab-paclitaxel in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. The study includes dose escalation phase and dose expansion phase.

Carlos E. Stahlhut Espinosa, Anna E. Maciag, Kyle A. Sullivan, Kanchan Singh, Nadege Gitego et al. (37 authors)

Cancer Research2026-04-03

10.1158/1538-7445.am2026-7104

Data from Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants

Carlos Stahlhut, Anna E. Maciag, Kyle A. Sullivan, Kanchan Singh, Nadege Gitego et al. (36 authors)

2026-04-01

10.1158/2159-8290.c.8395777

Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants.

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.

2026-03-06

10.1158/2159-8290.cd-25-1280

Abstract C082: BBO-10203, a first-in-class, orally bioavailable, selective breaker of the RAS:PI3Kα interaction inhibits tumor growth alone and in combination with KRAS inhibitors in KRAS mutant models without inducing hyperglycemia

Kerstin W. Sinkevicius, James P. Stice, Rui Xu, Cathy Zhang, Siyu Feng et al. (34 authors)

Molecular Cancer Therapeutics2025-10-22

10.1158/1535-7163.targ-25-c082

Abstract A063: BBO-11818: an orally bioavailable, highly potent and selective non-covalent pan-KRAS(ON) and (OFF) inhibitor with robust anti-tumor activity in KRAS-mutant preclinical models

Carlos Stahlhut, Anna Maciąg, Kyle A. Sullivan, Kanchan Singh, Nadege Gitego et al. (36 authors)

Molecular Cancer Therapeutics2025-10-22

10.1158/1535-7163.targ-25-a063

Interventions

DRUGBBO-11818

Participants will receive assigned dose of BBO-11818 orally (PO)

DRUGPembrolizumab

Patients will receive IV pembrolizumab

DRUGPlatinum chemotherapy (cisplatin or carboplatin)

Patients will receive IV platinum chemotherapy (cisplatin or carboplatin)

DRUGPemetrexed

Patients will receive IV pemetrexed

DRUGCetuximab

Patients will receive IV cetuximab

DRUGFOLFOX

Patients will receive IV FOLFOX

DRUGNALIRIFOX

Patients will receive IV NALIRIFOX

DRUGGemcitabine

Patients will receive IV Gemcitabine

DRUGNab-paclitaxel

Patients will receive IV Nab-Paclitaxel

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Phase 1a: sequential/parallel, Phase 1b: parallel

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* 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

Exclusion criteria

* Malignancy within the last 2 years as specified in the protocol * Untreated brain metastases * Known hypersensitivity to BBO-11818 or its excipients Other inclusion/

Design outcomes

Primary

Measure	Time frame
Incidence and severity of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)	approximately 5 years
Determine recommended dose of BBO-11818 in combination with pembrolizumab +/- cis/carboplatin + pemetrexed, or cetuximab +/- FOLFOX, NALIRIFOX, or Gemcitabine + Nab-paclitaxel	approximately 5 years

Secondary

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

Countries

United States

Contacts

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

tbbo11818-101ct.gov@bbotx.com

Outcome results

None listed