BBO-11818 in Adult Subjects With KRAS Mutant Cancer

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

Status and phase: Enrolling; Phase 1

Conditions: KRAS G12V; Solid Tumor, Adult; Metastatic Colorectal Cancer (CRC); Non-Small Cell Lung Cancer; PDAC - Pancreatic Ductal Adenocarcinoma; Metastatic Non-Small Lung Cell Cancer; Advanced Lung Carcinoma; CRC (Colorectal Cancer); KRAS G12A; Metastatic Pancreatic Ductal Adenocarcinoma; KRAS G12C; KRAS G12S; KRAS G12D; NSCLC

Treatments: Drug: BBO-11818; Drug: FOLFOX; Drug: NALIRIFOX; Drug: Platinum chemotherapy (cisplatin or carboplatin); Drug: Cetuximab; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Pemetrexed; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06917079

TBBO11818-101

KONQUER-101 (Other Identifier)

Details and patient eligibility

About

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.

Full 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 +/- FOLFOX, NALIRIFOX, or Gemcitabine + Nab-paclitaxel in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. The study includes dose escalation phase and dose expansion phase.

Enrollment: 387 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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387 participants in 14 patient groups

Cohort 1a - Dose Escalation Monotherapy

Experimental group

Description:

Participants enrolled in this cohort will receive BBO-11818 as monotherapy

Treatment:

Drug: BBO-11818

Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab)

Experimental group

Description:

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

Treatment:

Drug: Pembrolizumab

Drug: BBO-11818

Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)

Experimental group

Description:

Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)

Treatment:

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: Platinum chemotherapy (cisplatin or carboplatin)

Drug: BBO-11818

Cohort 1d - Dose Escalation Combination Therapy (Cetuximab)

Experimental group

Description:

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

Treatment:

Drug: Cetuximab

Drug: BBO-11818

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

Experimental group

Description:

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

Treatment:

Drug: Cetuximab

Drug: FOLFOX

Drug: BBO-11818

Cohort 1f - Dose Escalation Combination Therapy (NALIRIFOX)

Experimental group

Description:

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

Treatment:

Drug: NALIRIFOX

Drug: BBO-11818

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

Experimental group

Description:

Participants enrolled in this cohort will receive BBO-11818 in combination with Gemcitabine infusion (IV) and Nab-Paclitaxel infusion (IV)

Treatment:

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: BBO-11818

Cohort 2a - Dose Expansion Monotherapy

Experimental group

Description:

Participants enrolled in this cohort will receive BBO-11818 as monotherapy

Treatment:

Drug: BBO-11818

Cohort 2b - Dose Expansion Combination (Pembrolizumab)

Experimental group

Description:

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

Treatment:

Drug: Pembrolizumab

Drug: BBO-11818

Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed)

Experimental group

Description:

Participants enrolled in this cohort will receive BBO-11818 in combination with pembrolizumab infusion (IV), cis/carboplatin infusion (IV), and pemetrexed infusion (IV)

Treatment:

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: Platinum chemotherapy (cisplatin or carboplatin)

Drug: BBO-11818

Cohort 2d - Dose Expansion Combination Therapy (Cetuximab)

Experimental group

Description:

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

Treatment:

Drug: Cetuximab

Drug: BBO-11818

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

Experimental group

Description:

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

Treatment:

Drug: Cetuximab

Drug: FOLFOX

Drug: BBO-11818

Cohort 2f - Dose Expansion Combination Therapy (NALIRIFOX)

Experimental group

Description:

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

Treatment:

Drug: NALIRIFOX

Drug: BBO-11818

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

Experimental group

Description:

Participants enrolled in this cohort will receive BBO-11818 in combination with Gemcitabine infusion (IV) and Nab-Paclitaxel infusion (IV)

Treatment:

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: BBO-11818