BBO-11818 in Adult Subjects With KRAS Mutant Cancer

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer; NSCLC; Advanced Lung Carcinoma; Solid Tumor, Adult; Metastatic Pancreatic Ductal Adenocarcinoma; PDAC - Pancreatic Ductal Adenocarcinoma; KRAS G12D; Metastatic Non-Small Lung Cell Cancer; KRAS G12V; KRAS G12C; Metastatic Colorectal Cancer (CRC); KRAS G12A; KRAS G12S; CRC (Colorectal Cancer)
• Intervention / Treatment: Drug: Pembrolizumab; Drug: BBO-11818; Drug: Platinum chemotherapy (cisplatin or carboplatin); Drug: Pemetrexed; Drug: Cetuximab; Drug: mFOLFOX6; Drug: mFOLFOX6; Drug: BBO-10203; Drug: mFOLFIRINOX; Drug: Gemcitabine; Drug: Nab-paclitaxel

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, 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.

• Study Type: Interventional
• Enrollment (Estimated): 665
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics); Phone Number: (650) 405-4770; Email: tbbo11818-101ct.gov@bbotx.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
      • Contact: Phone Number: 03-8559-5000
• United States
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • The Angeles Clinic and Research Institute - West Los Angeles Office
      • Contact: Phone Number: 310-582-7900
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California Davis
      • Contact: Phone Number: 916-734-5959
    • San Diego, California, United States, 92037
      • Recruiting
      • University Of California San Diego Moores Cancer Center
      • Contact: Phone Number: 858-822-6100
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco Helen Diller Family Comprehensive Cancer Center
      • Contact: Phone Number: 415-885-7796
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University
      • Contact: Phone Number: 203-200-2486
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Phone Number: 888-663-3488
  • Illinois
    • Peoria, Illinois, United States, 61637
      • Recruiting
      • OSF Healthcare Cancer Institute
      • Contact: Phone Number: 309-308-3800
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Phone Number: 617-724-4000
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Phone Number: 646-929-7870
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Phone Number: 877-426-5637
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Phone Number: 615-936-8422
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Sarah Cannon Research Institute at Mary Crowley
      • Contact: Phone Number: 972-566-3000
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Phone Number: 877-632-6789
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology
      • Contact: Phone Number: 210-580-9500
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute
      • Contact: Phone Number: 801-587-7000
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center
      • Contact: Phone Number: 206-667-5000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• Life expectancy >24 weeks
• Adequate organ function

Exclusion Criteria:

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

Other inclusion/exclusion criteria are specified in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

20

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a - Dose Escalation Monotherapy; Participants enrolled in this cohort will receive BBO-11818 as monotherapy	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO)
Experimental: Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab); Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)	Drug: Pembrolizumab; Patients will receive IV pembrolizumab; Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO)
Experimental: Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed); Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)	Drug: Pembrolizumab; Patients will receive IV pembrolizumab; Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Platinum chemotherapy (cisplatin or carboplatin); Patients will receive IV platinum chemotherapy (cisplatin or carboplatin); Drug: Pemetrexed; Patients will receive IV pemetrexed
Experimental: Cohort 2a - Dose Expansion Monotherapy; Participants enrolled in this cohort will receive BBO-11818 as monotherapy	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO)
Experimental: Cohort 2b - Dose Expansion Combination (Pembrolizumab); Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)	Drug: Pembrolizumab; Patients will receive IV pembrolizumab; Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO)
Experimental: Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed); Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)	Drug: Pembrolizumab; Patients will receive IV pembrolizumab; Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Platinum chemotherapy (cisplatin or carboplatin); Patients will receive IV platinum chemotherapy (cisplatin or carboplatin); Drug: Pemetrexed; Patients will receive IV pemetrexed
Experimental: Cohort 1d - Dose Escalation Combination Therapy (Cetuximab ± mFOLFOX6); Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV) with or without mFOLFOX6 infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Cetuximab; Patients will receive IV cetuximab; Drug: mFOLFOX6; Patients may receive IV mFOLFOX6; Drug: mFOLFOX6; Patients will receive IV mFOLFOX6
Experimental: Cohort 1e - Dose Escalation Combination Therapy (BBO-10203 + mFOLFOX6); Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203 and mFOLFOX6 infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: mFOLFOX6; Patients may receive IV mFOLFOX6; Drug: mFOLFOX6; Patients will receive IV mFOLFOX6; Drug: BBO-10203; Participants will receive BBO-10203 orally (PO)
Experimental: Cohort 1f - Dose Escalation Combination Therapy (BBO-10203 + Cetuximab); Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203 and cetuximab infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Cetuximab; Patients will receive IV cetuximab; Drug: BBO-10203; Participants will receive BBO-10203 orally (PO)
Experimental: Cohort 1g - Dose Escalation Combination Therapy (Cetuximab); Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Cetuximab; Patients will receive IV cetuximab
Experimental: Cohort 1h - Dose Escalation Combination Therapy (mFOLFIRINOX); Participants enrolled in this cohort will receive BBO-11818 in combination with mFOLFIRINOX infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: mFOLFIRINOX; Patients will receive IV mFOLFIRINOX
Experimental: Cohort 1i - Dose Escalation Combination Therapy (Gemcitabine + Nab-paclitaxel); Participants enrolled in this cohort will receive BBO-11818 in combination with gemcitabine infusion (IV) and nab-paclitaxel infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Gemcitabine; Patients will receive IV gemcitabine; Drug: Nab-paclitaxel; Patients will receive IV nab-paclitaxel
Experimental: Cohort 1j - Dose Escalation Combination Therapy (BBO-10203); Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: BBO-10203; Participants will receive BBO-10203 orally (PO)
Experimental: Cohort 2d - Dose Expansion Combination Therapy (Cetuximab ± mFOLFOX6); Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV) with or without mFOLFOX6 infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Cetuximab; Patients will receive IV cetuximab; Drug: mFOLFOX6; Patients may receive IV mFOLFOX6; Drug: mFOLFOX6; Patients will receive IV mFOLFOX6
Experimental: Cohort 2e - Dose Expansion Combination Therapy (BBO-10203 + mFOLFOX6); Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203 and mFOLFOX6 infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: mFOLFOX6; Patients may receive IV mFOLFOX6; Drug: mFOLFOX6; Patients will receive IV mFOLFOX6; Drug: BBO-10203; Participants will receive BBO-10203 orally (PO)
Experimental: Cohort 2f - Dose Expansion Combination Therapy (BBO-10203 + Cetuximab); Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203 and cetuximab infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Cetuximab; Patients will receive IV cetuximab; Drug: BBO-10203; Participants will receive BBO-10203 orally (PO)
Experimental: Cohort 2g - Dose Expansion Combination Therapy (Cetuximab); Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Cetuximab; Patients will receive IV cetuximab
Experimental: Cohort 2h - Dose Expansion Combination Therapy (mFOLFIRINOX); Participants enrolled in this cohort will receive BBO-11818 in combination with mFOLFIRINOX infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: mFOLFIRINOX; Patients will receive IV mFOLFIRINOX
Experimental: Cohort 2i - Dose Expansion Combination Therapy (Gemcitabine + Nab-paclitaxel); Participants enrolled in this cohort will receive BBO-11818 in combination with gemcitabine infusion (IV) and nab-paclitaxel infusion (IV)	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: Gemcitabine; Patients will receive IV gemcitabine; Drug: Nab-paclitaxel; Patients will receive IV nab-paclitaxel
Experimental: Cohort 2j - Dose Expansion Combination Therapy (BBO-10203); Participants enrolled in this cohort will receive BBO-11818 in combination with BBO-10203	Drug: BBO-11818; Participants will receive assigned dose of BBO-11818 orally (PO); Drug: BBO-10203; Participants will receive BBO-10203 orally (PO)

What is the study measuring?

Primary Outcome Measures

Outcome 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, cetuximab ± mFOLFOX6, BBO-10203 + mFOLFOX6, BBO-10203 + cetuximab, cetuximab, mFOLFIRINOX, gemcitabine + nab-paclitaxel, or BBO-10203	approximately 5 years

Secondary Outcome Measures

Outcome 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, BBO-10203, irinotecan, and its metabolites (SN-38 and SN-38-G): Maximum blood concentration (Cmax)	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)	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)	approximately 5 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: April 1, 2025
• First Submitted That Met QC Criteria: April 1, 2025
• First Posted (Actual): April 8, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Gemcitabine; NSCLC; Pembrolizumab; Cetuximab; Pemetrexed; Advanced Cancer; Metastatic Cancer; CRC; Phase1; Nab-paclitaxel; PDAC; mFOLFIRINOX; mFOLFOX6; Phase 1a/1b; BridgeBio Oncology Therapeutics; BBOT; Platinum Chemotherapy; KONQUER; KONQUER-101
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Neoplastic Processes; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Pemetrexed; Cetuximab; Gemcitabine; Carboplatin; Cisplatin; pembrolizumab; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: TBBO11818-101; KONQUER-101 (Other Identifier: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No