BBO-11818 in Adult Subjects With KRAS Mutant Cancer

Phase 1

Recruiting

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

• Registration Number: NCT06917079
• Lead Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

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, or cetuximab in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. The study includes dose escalation phase and dose expansion phase.

Study Timeline

• Study Start: 2025-03-31
• Status Verified: 2025-04
• Study First Submitted: 2025-04-01
• Study First Submitted QC: 2025-04-01
• Study First Posted: 2025-04-08
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-04
• Primary Completion: 2027-08
• Study Completion: 2029-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 287

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, or KRAS-amplification
• 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/exclusion criteria are specified in the protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1a - Dose Escalation Monotherapy	BBO-11818	Participants enrolled in this cohort will receive BBO-11818 as monotherapy
Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab)	BBO-11818	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)
Cohort 2d - Dose Expansion Combination Therapy (Cetuximab)	BBO-11818	Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)
Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab)	Pembrolizumab	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)
Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)	BBO-11818	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)	Pembrolizumab	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)	Platinum chemotherapy (cisplatin or carboplatin)	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)	Pemetrexed	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
Cohort 1d - Dose Escalation Combination Therapy (Cetuximab)	BBO-11818	Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)
Cohort 1d - Dose Escalation Combination Therapy (Cetuximab)	Cetuximab	Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)
Cohort 2a - Dose Expansion Monotherapy	BBO-11818	Participants enrolled in this cohort will receive BBO-11818 as monotherapy
Cohort 2b - Dose Expansion Combination (Pembrolizumab)	BBO-11818	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)
Cohort 2b - Dose Expansion Combination (Pembrolizumab)	Pembrolizumab	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV)
Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)	BBO-11818	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)	Pembrolizumab	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)	Platinum chemotherapy (cisplatin or carboplatin)	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)	Pemetrexed	Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)
Cohort 2d - Dose Expansion Combination Therapy (Cetuximab)	Cetuximab	Participants enrolled in this cohort will receive BBO-11818 in combination with cetuximab infusion (IV)

Primary Outcome Measures

Name	Time	Method
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	approximately 5 years

Secondary Outcome Measures

Name	Time	Method
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: Maximum blood concentration (Cmax)	approximately 5 years
Pharmacokinetics of BBO-11818: Time to achieve Cmax (Tmax)	approximately 5 years
Pharmacokinetics of BBO-11818: Area under the concentration-time curve (AUC)	approximately 5 years

Trial Locations

Locations (4)

Sarah Cannon Research Institute at Mary Crowley; 🇺🇸 Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States