BBO-8520 + Pembrolizumab for Lung Cancer

Recruiting at 20 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, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, BBO-8520, for individuals with advanced lung cancer that has a specific mutation called KRAS G12C. Researchers aim to determine if BBO-8520 is safe and effective in shrinking tumors, either alone or with pembrolizumab (a type of immunotherapy). Participants will join different groups receiving either BBO-8520 alone or in combination with pembrolizumab, with varying doses to identify the most effective and safe option. The trial seeks individuals with non-small cell lung cancer that cannot be surgically removed and has this specific mutation. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that BBO-8520, a new treatment for lung cancer, is in early testing stages. Current studies are examining its safety when used alone and with pembrolizumab, a drug already used to treat cancer.

The FDA has granted BBO-8520 "fast track" status, indicating it could meet an unmet need. This designation is promising but does not guarantee safety. As this is an early trial, researchers are still gathering safety information. The trial aims to find the best dose that avoids harmful effects.

Pembrolizumab is already available for other cancers and is generally well-tolerated, though some patients may experience side effects like tiredness or a rash.

In summary, while pembrolizumab has a known safety record, BBO-8520 is still under study. More information is needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BBO-8520 for lung cancer because it offers a fresh approach compared to standard treatments like chemotherapy and targeted therapies. BBO-8520 works uniquely by targeting specific pathways that might help the immune system recognize and attack cancer cells more effectively. When combined with pembrolizumab, an established immunotherapy drug, there's potential for a powerful synergy that could enhance the body's ability to fight the tumor. This combination therapy could offer a promising new option for patients, especially those who might not respond well to current treatments.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will evaluate BBO-8520, which targets a specific change in non-small cell lung cancer (NSCLC) called KRAS G12C, to help inhibit cancer growth. In studies with mice, BBO-8520 effectively shrank tumors. Early human tests have assessed its safety and initial effects against cancer. Participants in this trial may receive BBO-8520 as monotherapy or combined with pembrolizumab, a well-known cancer drug that boosts the immune system. Pembrolizumab alone has shown a survival benefit over five years in similar cases, suggesting that the combination could be promising. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with a specific mutation in their lung cancer cells (KRASG12C). Participants should have advanced non-small cell lung cancer that has progressed despite previous treatment. The study excludes individuals who don't meet the health requirements or have conditions that could interfere with the drug's effects.

Inclusion Criteria

I am fully active or can carry out light work.

Measurable disease by RECIST v1.1

My lung cancer is advanced or has spread, and tests show a KRAS G12C mutation.

Exclusion Criteria

I have had cancer within the last 2 years.

Patients with known hypersensitivity to BBO-8520 or its excipients

For Cohorts 2a and 2b: Patients with a known hypersensitivity to pembrolizumab or its excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BBO-8520 at different dose levels, alone or in combination with pembrolizumab, to evaluate safety and determine optimal dosing

12-24 weeks

Dose Expansion

Participants receive BBO-8520 at the determined dose, alone or in combination with pembrolizumab, to further evaluate safety and preliminary antitumor activity

24-48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BBO-8520
• Pembrolizumab

Trial Overview The trial is testing BBO-8520, a new potential drug targeting KRAS G12C mutations in lung cancer cells. It will be given alone and alongside pembrolizumab, an existing cancer therapy, to evaluate safety, how well it's tolerated by patients, and its behavior in the body.

How Is the Trial Designed?

Group I: Cohort 2b - Dose Expansion Combination Therapy Experimental Treatment 2 Interventions

Participants enrolled in this cohort will receive BBO-8520 once a day (QD) in combination with pembrolizumab infusion (IV)

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

Participants enrolled in this cohort will receive BBO-8520 once a day (QD) as monotherapy

Group III: Cohort 1b - Dose Escalation/Dose Finding Combination Therapy Experimental Treatment 2 Interventions

Participants enrolled in this cohort will receive BBO-8520 (different dose levels will be evaluated) once a day (QD) in combination with pembrolizumab infusion (IV)

Group IV: Cohort 1a - Dose Escalation/Dose Finding Monotherapy Experimental Treatment 1 Intervention

Participants enrolled in this cohort will receive BBO-8520 (different dose levels will be evaluated) once a day (QD) as monotherapy

BBO-8520 is already approved in United States for the following indications:

Approved in United States as BBO-8520 for:

• None approved; Fast Track designation for KRAS G12C-mutated metastatic non-small cell lung cancer

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2

Recruited

400+

TheRas, Inc

Lead Sponsor

Trials

1

Recruited

250+

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

Lead Sponsor

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a study of 72 treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, pembrolizumab showed an objective response rate of 45.8%, with even higher rates of 70.0% in patients with pre-existing interstitial lung disease (ILD).

Patients with ILD had similar overall survival rates compared to those without ILD, suggesting that pembrolizumab can be safely administered to NSCLC patients with ILD without compromising their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. Yamaguchi, O., Kaira, K., Shinomiya, S., et al.[2021]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., et al.[2022]

In a multicenter observational study involving 300 patients with non-small cell lung cancer (NSCLC), pembrolizumab demonstrated a median overall survival of 558 days and a progression-free survival of 188 days, indicating its efficacy in real-world settings.

The study confirmed that factors such as performance status and PD-L1 expression significantly influenced overall survival, while the toxicity profile of pembrolizumab remained consistent with previous reports, suggesting it is a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data. Terai, H., Soejima, K., Shimokawa, A., et al.[2022]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS8649

Onkoras-101: A phase 1a/1b open-label study evaluating ... BBO-8520 is being developed to treat patients with advanced cancer harboring the KRASG12C mutation. The oncogenic KRASG12C mutation results in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06343402

NCT06343402 | Open-label Study of BBO-8520 in Adult ... A first in human study to evaluate the safety and preliminary antitumor activity of BBO-8520, a KRAS G12C (ON and OFF) inhibitor, as a single agent and in ...

3. aacrjournals.org aacrjournals.org/cancerdiscovery/article/15/3/578/752121/Discovery-of-BBO-8520-a-First-In-Class-Direct-and

Discovery of BBO-8520, a First-In-Class Direct and Covalent ... E, In the KCP NSCLC GEMM, BBO- 8520 demonstrated significant and robust efficacy at 10 mg/kg (*, P < 0.0001). F, In the CT26-KRASG12C-luciferase ...

4. ilcn.org ilcn.org/in-brief-for-february-12-2025/

In Brief for February 12, 2025 - ILCN.org (ILCN/WCLC) BBO-8520 Receives Fast Track Designation from the FDA for KRAS G12C-Mutant mNSCLC · China Approves Taletrectinib for Advanced ROS1-Positive NSCLC.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11974359/

Beyond First-Generation KRAS Inhibitors: BBO-8520 Tests ... The ongoing phase I trial of BBO-8520 will be pivotal in determining whether its mechanistic advantages translate to superior clinical efficacy.

6. onclive.com onclive.com/view/bbo-8520-receives-fda-fast-track-designation-in-kras-g12c-mutated-metastatic-nsclc

BBO-8520 Receives FDA Fast Track Designation in KRAS ... BBO-8520 has received FDA fast track designation in previously treated KRAS G12C–mutated metastatic non–small cell lung cancer.