Mass General - Division of Clinical Research

BBO-11818 in Adult Subjects With KRAS Mutant Cancer

Purpose

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

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts 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 - 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 Design

Phase: Phase 1
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1a: sequential/parallel, Phase 1b: parallel
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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: BBO-11818 Participants will receive assigned dose of BBO-11818 orally (PO) Drug: Pembrolizumab Patients will receive IV pembrolizumab
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: BBO-11818 Participants will receive assigned dose of BBO-11818 orally (PO) Drug: Pembrolizumab Patients will receive IV pembrolizumab 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
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 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 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: BBO-11818 Participants will receive assigned dose of BBO-11818 orally (PO) Drug: Pembrolizumab Patients will receive IV pembrolizumab
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: BBO-11818 Participants will receive assigned dose of BBO-11818 orally (PO) Drug: Pembrolizumab Patients will receive IV pembrolizumab Drug: Platinum chemotherapy (cisplatin or carboplatin) Patients will receive IV platinum chemotherapy (cisplatin or carboplatin) Drug: Pemetrexed Patients will receive IV pemetrexed
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
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 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)

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

Contact:
617-724-4000

More Details

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

Study Contact

TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)
(650) 405-4770
tbbo11818-101ct.gov@bbotx.com

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.