BBO-8520 + Pembrolizumab for Lung Cancer
Recruiting in Palo Alto (17 mi)
+14 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics
Disqualifiers: Recent malignancy, Untreated brain metastases, Autoimmune disease, others
No Placebo Group
Breakthrough Therapy
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.
12345What 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.
12678What 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.
124910Eligibility 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
+3 more
Trial 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
Participant Groups
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.
4Treatment groups
Experimental Treatment
Group I: Cohort 2b - Dose Expansion Combination TherapyExperimental Treatment2 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 MonotherapyExperimental Treatment1 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 TherapyExperimental Treatment2 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 MonotherapyExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
SCRI Oncology PartnersNashville, TN
Cleveland ClinicCleveland, OH
Norwalk HospitalNorwalk, CT
NEXT OncologyFairfax, VA
More Trial Locations
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Who Is Running the Clinical Trial?
TheRas, Inc., d/b/a BridgeBio Oncology TherapeuticsLead Sponsor
TheRas, IncLead Sponsor
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.
Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science.
Pembrolizumab Shows Promise for NSCLC. [2015]Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
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]The safety of pembrolizumab monotherapy in treatment-naïve non-small cell lung cancer (NSCLC) patients with high programed death-ligand 1 (PD-L1) expression and pre-existing interstitial lung disease (ILD) has not yet been determined. Here, we aimed to evaluate the prognosis, efficacy and safety associated with pembrolizumab in such settings.
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]Pembrolizumab is a standard-of-care for advanced non-small-cell lung cancer (NSCLC). We assessed pembrolizumab as adjuvant therapy for completely resected stage IB-IIIA NSCLC.
Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data. [2022]Pembrolizumab is a programmed death-ligand 1 inhibitor that was initially indicated for monotherapy in patients with advanced lung cancer. The Japanese Lung Cancer Society conducted an observational study on pembrolizumab using confirmative data obtained through postmarketing all-case surveillance (PMACS), which was performed by a pharmaceutical company under the Japanese law in 2017.