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, 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

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

ArmDescriptionAssigned 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) 		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 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) 		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

Recruiting Locations

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114

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)
650-391-9740
tbbo11818-101ct.gov@bridgebiooncology.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, or cetuximab in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. The study includes dose escalation phase and dose expansion phase.