BBO-11818 for KRAS Mutant Cancer

Recruiting at 3 trial locations

Overseen By TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

Disqualifiers: Recent malignancy, Untreated brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

287 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug BBO-11818 for KRAS mutant cancer?

Research shows that combining different inhibitors, like MEK and PI3K, with RAF inhibitors can be effective in treating KRAS mutant tumors. This suggests that using a combination approach might help in making KRAS mutant tumors more sensitive to treatment. ^{1 2 3 4 5}

What makes the drug BBO-11818 unique for treating KRAS mutant cancer?

BBO-11818 may offer a novel approach by potentially targeting KRAS mutant tumors through a mechanism involving RAF inhibitors, which have shown limited success alone but may work better in combination with other inhibitors like MEK and PI3K. This strategy could help make KRAS mutant tumors more sensitive to treatment, offering a new angle compared to existing therapies. ^{1 2 6 7 8}

What is the purpose of this trial?

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.

Eligibility Criteria

Adults with advanced or metastatic solid tumors that have a KRAS mutation can join this trial. Specific cancers include non-small cell lung cancer, colon, pancreatic, colorectal, and stomach cancers. Participants must not be eligible for surgery to remove their tumors.

Inclusion Criteria

Measurable disease by RECIST v1.1

I am fully active or can carry out light work.

My cancer is advanced, cannot be surgically removed, and has a specific KRAS mutation.

Exclusion Criteria

Known hypersensitivity to BBO-11818 or its excipients

I was diagnosed with cancer within the last 2 years.

I have brain metastases that have not been treated.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BBO-11818 alone or in combination with other therapies to determine the optimal dose

8-12 weeks

Dose Expansion

Participants receive BBO-11818 at the determined dose to further evaluate safety and efficacy

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• BBO-11818

Trial Overview The study is testing BBO-11818's safety and its ability to shrink tumors in patients with KRAS mutations. It's an early-stage trial where BBO-11818 is given alongside standard treatments like Pembrolizumab (immunotherapy), Platinum chemotherapy (cisplatin or carboplatin), Cetuximab (antibody therapy), and Pemetrexed (chemotherapy).

Participant Groups

Group I: Cohort 2d - Dose Expansion Combination Therapy (Cetuximab) Experimental Treatment 2 Interventions

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

Group II: Cohort 2c - Dose Expansion Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed) Experimental Treatment 4 Interventions

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

Group III: Cohort 2b - Dose Expansion Combination (Pembrolizumab) Experimental Treatment 2 Interventions

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

Group IV: Cohort 2a - Dose Expansion Monotherapy Experimental Treatment 1 Intervention

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

Group V: Cohort 1d - Dose Escalation Combination Therapy (Cetuximab) Experimental Treatment 2 Interventions

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

Group VI: Cohort 1c - Dose Escalation Combination Therapy (Pembrolizumab + Cis/carboplatin + Pemetrexed) Experimental Treatment 4 Interventions

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

Group VII: Cohort 1b - Dose Escalation Combination Therapy (Pembrolizumab) Experimental Treatment 2 Interventions

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

Group VIII: Cohort 1a - Dose Escalation Monotherapy Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

Lead Sponsor

Trials

2

Recruited

400+

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

Lead Sponsor

Findings from Research

KRAS is a commonly mutated oncogene in aggressive solid tumors like colorectal, lung, and pancreatic cancer, making it a critical target for cancer treatment.

Recent advancements have led to the approval of specific inhibitors for the KRAS G12C mutation, such as adagrasib and sotorasib, for treating lung cancer, marking a significant step forward in targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Mutated KRAS Genes to Treat Solid Tumours. Krishnan, T., Roberts-Thomson, R., Broadbridge, V., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacological Induction of RAS-GTP Confers RAF Inhibitor Sensitivity in KRAS Mutant Tumors. [2019]

2. England pubmed.ncbi.nlm.nih.gov

KRAS mutant tumor subpopulations can subvert durable responses to personalized cancer treatments. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Dasatinib sensitises KRAS-mutant cancer cells to mitogen-activated protein kinase kinase inhibitor via inhibition of TAZ activity. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Targeting Mutated KRAS Genes to Treat Solid Tumours. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Targeting the undruggable oncogenic KRAS: the dawn of hope. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment Strategies for KRAS-Mutated Non-Small-Cell Lung Cancer. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Dimerization Is Critical for the Functions of Wild-type and Mutant KRAS. [2019]