PBF-1129 + Nivolumab for Lung Cancer

Overseen by Dwight Owen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Dwight Owen

Must be taking: PD-1, PD-L1 therapies

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, Immunodeficiency, Infections, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing PBF-1129 and nivolumab in patients with advanced lung cancer. The goal is to see if these drugs can work together to stop cancer growth and boost the immune system's ability to fight the cancer. Nivolumab has shown effectiveness in treating various cancers, including non-small cell lung cancer.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive drugs, you may need to stop them before starting the trial.

What data supports the effectiveness of the drug Nivolumab for lung cancer?

Nivolumab has been shown to significantly improve overall survival and response rates in patients with advanced non-small cell lung cancer (NSCLC) compared to the chemotherapy drug docetaxel, as demonstrated in the CheckMate 017 and CheckMate 057 trials. ^{1 2 3 4 5}

Is the combination of PBF-1129 and Nivolumab safe for humans?

Nivolumab, also known as Opdivo, has been studied in lung cancer and is generally well-tolerated, with manageable side effects, including immune-related reactions. However, when combined with other treatments, like in immune checkpoint blockade, side effects can be more frequent and severe, requiring careful monitoring and management. ^{1 2 4 6 7}

What makes the drug combination of PBF-1129 and Nivolumab unique for lung cancer treatment?

The combination of PBF-1129 and Nivolumab is unique because it combines an adenosine A2B receptor antagonist (PBF-1129) with a PD-1 immune checkpoint inhibitor (Nivolumab), potentially enhancing the immune system's ability to fight lung cancer by targeting different pathways. This approach may offer a novel mechanism compared to standard treatments that typically focus on a single pathway. ^{1 2 4 6 8}

Research Team

Dwight Owen, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

Adults with recurrent or metastatic non-small cell lung cancer who have tried standard treatments, including chemotherapy and immunotherapy. They must have good organ function, no untreated brain metastases, no active infections like HIV/Hepatitis B or C, not be pregnant/breastfeeding, and willing to use contraception. Prior PD-1/PD-L1 therapy is required; prior CTLA4 therapy is okay.

Inclusion Criteria

You have a recent tumor tissue sample stored in a special way, or you can provide unstained slides with tissue samples from a recent tumor biopsy or surgery.

Your albumin levels are at least 2.5 mg/dL.

Your blood clotting time is not too fast or too slow, unless you are taking medication to control it.

Exclusion Criteria

You have brain metastases that have not been treated yet. If you have already been treated for brain metastases and are doing well, you may still be eligible.

You had bad side effects from a previous treatment with a checkpoint inhibitor.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PBF-1129 orally once daily and nivolumab intravenously on day 1 of each 28-day cycle

Up to 1 year

Monthly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Every 12 weeks

Treatment Details

Interventions

• Nivolumab (Checkpoint Inhibitor)
• PBF-1129 (Adenosine A2B Receptor Antagonist)

Trial Overview The trial tests PBF-1129 combined with nivolumab to determine the safest dose and side effects for treating non-small cell lung cancer that has returned or spread. It explores how these drugs might help the immune system fight cancer by inhibiting tumor growth.

Participant Groups

Group I: Treatment (PBF-1129, nivolumab) Experimental Treatment 3 Interventions

Patients receive PBF-1129 PO QD and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Nivolumab is already approved in Canada, Switzerland for the following indications:

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Dwight Owen

Lead Sponsor

Trials

6

Recruited

210+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

In a retrospective study of patients with pulmonary adenocarcinomas treated with nivolumab, no significant differences were found in objective response rates or progression-free survival based on previous chemotherapy regimens.

However, there was a trend indicating that patients previously treated with carboplatin plus taxanes or vinorelbine (with or without bevacizumab) had better overall survival compared to those treated with cisplatin and pemetrexed, suggesting that the former may be a more effective combination for immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Previous Chemotherapy Affect the Outcome of Nivolumab Treatment in Non-small Cell Lung Cancer? Svaton, M., Bratova, M., Koubkova, L., et al.[2022]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

In a study of 79 pre-treated patients with advanced non-small cell lung cancer, nivolumab significantly prolonged progression-free survival, especially in patients who had a partial response to prior treatments.

The occurrence of skin rash during nivolumab treatment was associated with improved long-term survival, suggesting that this side effect may indicate a favorable response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. Akano, Y., Kuribayashi, K., Funaguchi, N., et al.[2020]

Combined immune checkpoint blockade (ICB) using nivolumab and ipilimumab shows significant efficacy in treating advanced melanoma, but it also leads to a higher frequency and severity of adverse drug reactions (ADRs) compared to single-agent therapies, based on pooled safety data from 1551 patients.

Most immune-related ADRs are reversible with glucocorticoids, but due to the increased risk and rapid onset of these toxicities, clinicians must be well-trained to monitor and manage these side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. Hassel, JC., Heinzerling, L., Aberle, J., et al.[2022]

A network meta-analysis of five trials showed that PD-1 inhibitors (pembrolizumab and nivolumab) had higher overall response rates (ORR) compared to the PD-L1 inhibitor (atezolizumab), particularly in patients with high PD-L1 expression.

Both pembrolizumab and nivolumab demonstrated superior overall survival (OS) benefits in various patient subgroups, but treatment decisions should also consider individual patient characteristics and safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis. Almutairi, AR., Alkhatib, N., Martin, J., et al.[2019]

References

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

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

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

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

3. Greece pubmed.ncbi.nlm.nih.gov

Can Previous Chemotherapy Affect the Outcome of Nivolumab Treatment in Non-small Cell Lung Cancer? [2022]

4. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]

6. Greece pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis. [2019]