BBO-11818 in Adult Subjects With KRAS Mutant Cancer

NCT06917079 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: TBBO11818-101KONQUER-101
• Study Type: interventional
• Target: 665
• Locations: 2 countries
• Sites: 17

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.

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; mFOLFOX6; mFOLFIRINOX; Gemcitabine; Nab-paclitaxel

Outcome Measures

Primary Outcomes (2)

• 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, cetuximab ± mFOLFOX6, BBO-10203 + mFOLFOX6, BBO-10203 + cetuximab, cetuximab, mFOLFIRINOX, gemcitabine + nab-paclitaxel, or BBO-10203

  approximately 5 years

Secondary Outcomes (8)

• 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

Study Arms (20)

Cohort 1a - Dose Escalation Monotherapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 as monotherapy

Drug: BBO-11818

Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)

Drug: BBO-11818; Drug: Pembrolizumab

Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)

Drug: BBO-11818; Drug: Pembrolizumab; Drug: Platinum chemotherapy (cisplatin or carboplatin); Drug: Pemetrexed

Cohort 1d - Dose Escalation Combination Therapy (Cetuximab ± mFOLFOX6)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV) with or without mFOLFOX6 infusion (IV)

Drug: BBO-11818; Drug: Cetuximab; Drug: mFOLFOX6

Cohort 1e - Dose Escalation Combination Therapy (BBO-10203 + mFOLFOX6)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203 and mFOLFOX6 infusion (IV)

Drug: BBO-11818; Drug: mFOLFOX6; Drug: BBO-10203

Cohort 1f - Dose Escalation Combination Therapy (BBO-10203 + Cetuximab)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203 and cetuximab infusion (IV)

Drug: BBO-11818; Drug: Cetuximab; Drug: BBO-10203

Cohort 1g - Dose Escalation Combination Therapy (Cetuximab)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)

Drug: BBO-11818; Drug: Cetuximab

Cohort 1h - Dose Escalation Combination Therapy (mFOLFIRINOX)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with mFOLFIRINOX infusion (IV)

Drug: BBO-11818; Drug: mFOLFIRINOX

Cohort 1i - Dose Escalation Combination Therapy (Gemcitabine + Nab-paclitaxel)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with gemcitabine infusion (IV) and nab-paclitaxel infusion (IV)

Drug: BBO-11818; Drug: Gemcitabine; Drug: Nab-paclitaxel

Cohort 1j - Dose Escalation Combination Therapy (BBO-10203)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203

Drug: BBO-11818; Drug: BBO-10203

Cohort 2a - Dose Expansion Monotherapy

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 as monotherapy

Drug: BBO-11818

Cohort 2b - Dose Expansion Combination (Pembrolizumab)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)

Drug: BBO-11818; Drug: Pembrolizumab

Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)

Drug: BBO-11818; Drug: Pembrolizumab; Drug: Platinum chemotherapy (cisplatin or carboplatin); Drug: Pemetrexed

Cohort 2d - Dose Expansion Combination Therapy (Cetuximab ± mFOLFOX6)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV) with or without mFOLFOX6 infusion (IV)

Drug: BBO-11818; Drug: Cetuximab; Drug: mFOLFOX6

Cohort 2e - Dose Expansion Combination Therapy (BBO-10203 + mFOLFOX6)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203 and mFOLFOX6 infusion (IV)

Drug: BBO-11818; Drug: mFOLFOX6; Drug: BBO-10203

Cohort 2f - Dose Expansion Combination Therapy (BBO-10203 + Cetuximab)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203 and cetuximab infusion (IV)

Drug: BBO-11818; Drug: Cetuximab; Drug: BBO-10203

Cohort 2g - Dose Expansion Combination Therapy (Cetuximab)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)

Drug: BBO-11818; Drug: Cetuximab

Cohort 2h - Dose Expansion Combination Therapy (mFOLFIRINOX)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with mFOLFIRINOX infusion (IV)

Drug: BBO-11818; Drug: mFOLFIRINOX

Cohort 2i - Dose Expansion Combination Therapy (Gemcitabine + Nab-paclitaxel)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with gemcitabine infusion (IV) and nab-paclitaxel infusion (IV)

Drug: BBO-11818; Drug: Gemcitabine; Drug: Nab-paclitaxel

Cohort 2j - Dose Expansion Combination Therapy (BBO-10203)

EXPERIMENTAL

Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203

Drug: BBO-11818; Drug: BBO-10203

Interventions

Pembrolizumab DRUG

Patients will receive IV pembrolizumab

Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab); Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed); Cohort 2b - Dose Expansion Combination (Pembrolizumab); Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)

Platinum chemotherapy (cisplatin or carboplatin) DRUG

Patients will receive IV platinum chemotherapy (cisplatin or carboplatin)

Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed); Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)

BBO-11818 DRUG

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

Cohort 1a - Dose Escalation Monotherapy; Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab); Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed); Cohort 1d - Dose Escalation Combination Therapy (Cetuximab ± mFOLFOX6); Cohort 1e - Dose Escalation Combination Therapy (BBO-10203 + mFOLFOX6); Cohort 1f - Dose Escalation Combination Therapy (BBO-10203 + Cetuximab); Cohort 1g - Dose Escalation Combination Therapy (Cetuximab); Cohort 1h - Dose Escalation Combination Therapy (mFOLFIRINOX); Cohort 1i - Dose Escalation Combination Therapy (Gemcitabine + Nab-paclitaxel); Cohort 1j - Dose Escalation Combination Therapy (BBO-10203); Cohort 2a - Dose Expansion Monotherapy; Cohort 2b - Dose Expansion Combination (Pembrolizumab); Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed); Cohort 2d - Dose Expansion Combination Therapy (Cetuximab ± mFOLFOX6); Cohort 2e - Dose Expansion Combination Therapy (BBO-10203 + mFOLFOX6); Cohort 2f - Dose Expansion Combination Therapy (BBO-10203 + Cetuximab); Cohort 2g - Dose Expansion Combination Therapy (Cetuximab); Cohort 2h - Dose Expansion Combination Therapy (mFOLFIRINOX); Cohort 2i - Dose Expansion Combination Therapy (Gemcitabine + Nab-paclitaxel); Cohort 2j - Dose Expansion Combination Therapy (BBO-10203)

Pemetrexed DRUG

Patients will receive IV pemetrexed

Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed); Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)

Cetuximab DRUG

Patients will receive IV cetuximab

Cohort 1d - Dose Escalation Combination Therapy (Cetuximab ± mFOLFOX6); Cohort 1f - Dose Escalation Combination Therapy (BBO-10203 + Cetuximab); Cohort 1g - Dose Escalation Combination Therapy (Cetuximab); Cohort 2d - Dose Expansion Combination Therapy (Cetuximab ± mFOLFOX6); Cohort 2f - Dose Expansion Combination Therapy (BBO-10203 + Cetuximab); Cohort 2g - Dose Expansion Combination Therapy (Cetuximab)

Gemcitabine DRUG

Patients will receive IV gemcitabine

Cohort 1i - Dose Escalation Combination Therapy (Gemcitabine + Nab-paclitaxel); Cohort 2i - Dose Expansion Combination Therapy (Gemcitabine + Nab-paclitaxel)

Nab-paclitaxel DRUG

Patients will receive IV nab-paclitaxel

Cohort 1i - Dose Escalation Combination Therapy (Gemcitabine + Nab-paclitaxel); Cohort 2i - Dose Expansion Combination Therapy (Gemcitabine + Nab-paclitaxel)

mFOLFOX6 DRUG

Patients may receive IV mFOLFOX6

Cohort 1d - Dose Escalation Combination Therapy (Cetuximab ± mFOLFOX6); Cohort 2d - Dose Expansion Combination Therapy (Cetuximab ± mFOLFOX6)

BBO-10203 DRUG

Participants will receive BBO-10203 orally (PO)

Cohort 1e - Dose Escalation Combination Therapy (BBO-10203 + mFOLFOX6); Cohort 1f - Dose Escalation Combination Therapy (BBO-10203 + Cetuximab); Cohort 1j - Dose Escalation Combination Therapy (BBO-10203); Cohort 2e - Dose Expansion Combination Therapy (BBO-10203 + mFOLFOX6); Cohort 2f - Dose Expansion Combination Therapy (BBO-10203 + Cetuximab); Cohort 2j - Dose Expansion Combination Therapy (BBO-10203)

mFOLFIRINOX DRUG

Patients will receive IV mFOLFIRINOX

Cohort 1h - Dose Escalation Combination Therapy (mFOLFIRINOX); Cohort 2h - Dose Expansion Combination Therapy (mFOLFIRINOX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (17)

The Angeles Clinic and Research Institute - West Los Angeles Office

Los Angeles, California, 90025, United States

RECRUITING

University of California Davis

Sacramento, California, 95817, United States

RECRUITING

University of California San Diego Moores Cancer Center

San Diego, California, 92037, United States

RECRUITING

University of California San Francisco Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

RECRUITING

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

OSF Healthcare Cancer Institute

Peoria, Illinois, 61637, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Sarah Cannon Research Institute at Mary Crowley

Dallas, Texas, 75230, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Related Publications (1)

• 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 Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants. Cancer Discov. 2026 Apr 1;16(4):740-759. doi: 10.1158/2159-8290.CD-25-1280.

  PMID: 41790032 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Neoplasm Metastasis

Interventions

pembrolizumab; Cisplatin; Carboplatin; Pemetrexed; Cetuximab; Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

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

CONTACT

(650) 405-4770; tbbo11818-101ct.gov@bbotx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 8, 2025
• Study Start: March 31, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): September 1, 2029
• Last Updated: June 2, 2026

Record last verified: 2026-05

Locations

US (16); AU (1)