NCT06917079

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
387

participants targeted

Target at P75+ for phase_1 nonsmall-cell-lung-cancer

Timeline
41mo left

Started Mar 2025

Typical duration for phase_1 nonsmall-cell-lung-cancer

Geographic Reach
1 country

11 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress25%
Mar 2025Sep 2029

Study Start

First participant enrolled

March 31, 2025

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

April 1, 2025

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 8, 2025

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2027

Expected
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2029

Last Updated

March 23, 2026

Status Verified

August 1, 2025

Enrollment Period

2.3 years

First QC Date

April 1, 2025

Last Update Submit

March 20, 2026

Conditions

Non-Small Cell Lung CancerNSCLCPDAC - Pancreatic Ductal AdenocarcinomaCRC (Colorectal Cancer)Metastatic Non-Small Lung Cell CancerMetastatic Colorectal Cancer (CRC)KRAS G12AKRAS G12CKRAS G12DKRAS G12SKRAS G12VMetastatic Pancreatic Ductal AdenocarcinomaAdvanced Lung CarcinomaSolid Tumor, Adult

Keywords

BBOTBridgeBio Oncology TherapeuticsPhase1Phase 1a/1bNSCLCCRCPDACMetastatic CancerAdvanced CancerPembrolizumabCetuximabPlatinum ChemotherapyPemetrexedKONQUERKONQUER-101FOLFOXNALIRIFOXGemcitabineNab-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, or cetuximab +/- FOLFOX, NALIRIFOX, or Gemcitabine + Nab-paclitaxel

    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

  • +3 more secondary outcomes

Study Arms (14)

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-11818Drug: 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-11818Drug: PembrolizumabDrug: Platinum chemotherapy (cisplatin or carboplatin)Drug: Pemetrexed

Cohort 1d - Dose Escalation Combination Therapy (Cetuximab)

EXPERIMENTAL

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

Drug: BBO-11818Drug: Cetuximab

Cohort 1e - Dose Escalation Combination Therapy (FOLFOX + Cetuximab)

EXPERIMENTAL

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

Drug: BBO-11818Drug: CetuximabDrug: FOLFOX

Cohort 1f - Dose Escalation Combination Therapy (NALIRIFOX)

EXPERIMENTAL

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

Drug: BBO-11818Drug: NALIRIFOX

Cohort 1g - 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-11818Drug: GemcitabineDrug: Nab-paclitaxel

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-11818Drug: 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-11818Drug: PembrolizumabDrug: Platinum chemotherapy (cisplatin or carboplatin)Drug: Pemetrexed

Cohort 2d - Dose Expansion Combination Therapy (Cetuximab)

EXPERIMENTAL

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

Drug: BBO-11818Drug: Cetuximab

Cohort 2e - Dose Expansion Combination Therapy (FOLFOX + Cetuximab)

EXPERIMENTAL

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

Drug: BBO-11818Drug: CetuximabDrug: FOLFOX

Cohort 2f - Dose Expansion Combination Therapy (NALIRIFOX)

EXPERIMENTAL

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

Drug: BBO-11818Drug: NALIRIFOX

Cohort 2g - 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-11818Drug: GemcitabineDrug: Nab-paclitaxel

Interventions

PembrolizumabDRUG

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-11818DRUG

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

Cohort 1a - Dose Escalation MonotherapyCohort 1b - Dose Escalation Combination Therapy (Pembrolizumab)Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)Cohort 1d - Dose Escalation Combination Therapy (Cetuximab)Cohort 1e - Dose Escalation Combination Therapy (FOLFOX + Cetuximab)Cohort 1f - Dose Escalation Combination Therapy (NALIRIFOX)Cohort 1g - Dose Escalation Combination Therapy (Gemcitabine + Nab-Paclitaxel)Cohort 2a - Dose Expansion MonotherapyCohort 2b - Dose Expansion Combination (Pembrolizumab)Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)Cohort 2d - Dose Expansion Combination Therapy (Cetuximab)Cohort 2e - Dose Expansion Combination Therapy (FOLFOX + Cetuximab)Cohort 2f - Dose Expansion Combination Therapy (NALIRIFOX)Cohort 2g - Dose Expansion Combination Therapy (Gemcitabine + Nab-Paclitaxel)
PemetrexedDRUG

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)
CetuximabDRUG

Patients will receive IV cetuximab

Cohort 1d - Dose Escalation Combination Therapy (Cetuximab)Cohort 1e - Dose Escalation Combination Therapy (FOLFOX + Cetuximab)Cohort 2d - Dose Expansion Combination Therapy (Cetuximab)Cohort 2e - Dose Expansion Combination Therapy (FOLFOX + Cetuximab)
FOLFOXDRUG

Patients will receive IV FOLFOX

Cohort 1e - Dose Escalation Combination Therapy (FOLFOX + Cetuximab)Cohort 2e - Dose Expansion Combination Therapy (FOLFOX + Cetuximab)
NALIRIFOXDRUG

Patients will receive IV NALIRIFOX

Cohort 1f - Dose Escalation Combination Therapy (NALIRIFOX)Cohort 2f - Dose Expansion Combination Therapy (NALIRIFOX)
GemcitabineDRUG

Patients will receive IV Gemcitabine

Cohort 1g - Dose Escalation Combination Therapy (Gemcitabine + Nab-Paclitaxel)Cohort 2g - Dose Expansion Combination Therapy (Gemcitabine + Nab-Paclitaxel)
Nab-paclitaxelDRUG

Patients will receive IV Nab-Paclitaxel

Cohort 1g - Dose Escalation Combination Therapy (Gemcitabine + Nab-Paclitaxel)Cohort 2g - Dose Expansion Combination Therapy (Gemcitabine + Nab-Paclitaxel)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

The Angeles Clinic and Research Institute - West Los Angeles Office

Los Angeles, California, 90025, United States

RECRUITING

University of California San Diego Moores Cancer Center

San Diego, California, 92037, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, 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

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

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 Mar 6:OF1-OF20. doi: 10.1158/2159-8290.CD-25-1280. Online ahead of print.

    PMID: 41790032DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungColorectal NeoplasmsNeoplasm Metastasis

Interventions

pembrolizumabCisplatinCarboplatinPemetrexedCetuximabFolfox protocolGemcitabine130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination ComplexesOrganic ChemicalsGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, DicarboxylicAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulinsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-Ring

Central Study Contacts

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

CONTACT

tbbo11818-101ct.gov@bbotx.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Phase 1a: sequential/parallel, Phase 1b: parallel
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

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

March 23, 2026

Record last verified: 2025-08

Locations

US(11)