BBO-8520 + Pembrolizumab for Lung Cancer

Recruiting at 14 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

Trial Summary

What is the purpose of this trial?

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 combination with pembrolizumab in subjects with locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS (Kirsten rat sarcoma) G12C mutation.

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.

What data supports the effectiveness of the drug BBO-8520 + Pembrolizumab for lung cancer?

Research shows that pembrolizumab, a part of this drug combination, has been effective in treating non-small cell lung cancer (NSCLC), especially in patients with high PD-L1 expression. It has improved clinical outcomes and is well tolerated, as seen in various studies, including the KEYNOTE-001 trial. ^{1 2 3 4 5}

What safety information is available for the treatment BBO-8520 + Pembrolizumab for lung cancer?

Pembrolizumab (also known as Keytruda) has been studied in various cancers, including lung cancer, and is generally considered safe, but it can cause side effects. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects like pneumonitis (lung inflammation) can occur in 1%-5% of patients. ^{1 2 6 7 8}

What makes the drug BBO-8520 + Pembrolizumab unique for lung cancer treatment?

This treatment combines BBO-8520 with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, and is already used for various cancers, including lung cancer. The combination may offer a novel approach by potentially enhancing the immune response against lung cancer compared to using Pembrolizumab alone. ^{1 2 4 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

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 (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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

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

Pembrolizumab Shows Promise for NSCLC. [2015]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

8. Singapore 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. [2021]

9. England 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. [2022]

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

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data. [2022]