DF6002 + Nivolumab for Advanced Cancer

Recruiting in Palo Alto (17 mi)

+62 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Bristol-Myers Squibb

Must be taking: Anticoagulants

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Rapidly progressive disease, cardiac illness, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, DF6002, alone and with an existing drug, Nivolumab, in patients with advanced solid tumors. These patients have cancers that are hard to treat with standard methods. DF6002 might help shrink or slow down tumors, while Nivolumab boosts the immune system to fight cancer.

Will I have to stop taking my current medications?

The trial requires that you stop any current anticancer treatments, immune therapies, cytokine therapies (except erythropoietin), and systemic steroid or immunosuppressive therapies before starting the study. If you are on anticoagulants due to a high risk of blood clots, you may need to continue them.

What data supports the effectiveness of the drug DF6002 + Nivolumab for advanced cancer?

Nivolumab, one of the drugs in the treatment, has shown to significantly improve survival and response rates in patients with advanced squamous non-small cell lung cancer, as seen in the CheckMate 017 trial. Additionally, combining nivolumab with another drug, ipilimumab, has achieved higher response rates in certain tumors, suggesting potential benefits of combination therapies. ^{1 2 3 4 5}

Is the combination of DF6002 and Nivolumab safe for humans?

Nivolumab, also known as Opdivo, has been used in various cancer treatments and is generally considered to have a manageable safety profile. Common side effects include fatigue, diarrhea, nausea, and rash, and there are risks of immune-related side effects. However, specific safety data for the combination of DF6002 and Nivolumab is not provided in the available research. ^{6 7 8 9 10}

What makes the drug DF6002 + Nivolumab unique for advanced cancer?

The combination of DF6002 and Nivolumab is unique because it pairs a novel treatment with an established immune checkpoint inhibitor, Nivolumab, which enhances the immune system's ability to fight cancer by blocking the PD-1 pathway. This combination aims to improve the effectiveness of cancer treatment by leveraging the immune system's natural defenses. ^{1 3 10 11 12}

Research Team

Clinical Trials

Principal Investigator

Dragonfly Therapeutics

Eligibility Criteria

This trial is for adults with advanced solid tumors where standard treatments have failed or don't exist. Participants should be relatively active and well (ECOG status 0-1), show signs of cancer, and have good blood, liver, and kidney function. They can't join if they've had serious heart issues, other cancers in the last 3 years (with some exceptions), recent major surgery, or are on certain medications like steroids.

Inclusion Criteria

My condition shows signs on exams or images.

I need blood thinners for certain health risks.

My advanced cancer has no standard treatment left or treatments have failed.

Exclusion Criteria

I have not had any cancer other than my current one in the last 3 years.

I have a serious heart condition or other major health issues.

I have been diagnosed with a significant blood clotting disorder.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive DF6002 as monotherapy or in combination with nivolumab to determine the maximum tolerated dose and recommended efficacy expansion dose

Up to 3 weeks

Weekly visits for dose-limiting toxicity assessment

Efficacy Expansion

Participants receive DF6002 in combination with nivolumab to evaluate safety, tolerability, and preliminary anti-tumor activity

Up to 2 years

Monthly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• DF6002 (Other)
• Nivolumab (Checkpoint Inhibitor)

Trial Overview The study is testing DF6002 alone and combined with Nivolumab to see how safe they are and how patients respond to them. Researchers want to know what levels of these drugs stay in the body, their effects on tumors, and any potential benefits for those with tough-to-treat cancers.

Participant Groups

Group I: Safety/PK/PD / Monotherapy / Subcutaneously or Intravenously Experimental Treatment 1 Intervention

Subcutaneous portion of the study is complete. Dosing DF6002 Q4W

Group II: Safety/PK/PD / Combination / Subcutaneously or Intravenously Experimental Treatment 2 Interventions

Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W

Group III: Efficacy Expansion / Combination / Subcutaneously or Intravenously / Non-Melanoma Experimental Treatment 2 Interventions

Subcutaneous portion of the study is complete. 2L+ non-melanoma skin cancer (including cSCC, BCC, and MCC) Dosing DF6002 Q4W Dosing nivolumab Q4W

Group IV: Efficacy Expansion / Combination / Subcutaneously or Intravenously / Melanoma Experimental Treatment 2 Interventions

Subcutaneous portion of the study is complete. 2L+ melanoma Dosing DF6002 Q4W Dosing nivolumab Q4W

Group V: Dose Escalation / Monotherapy / Subcutaneously or Intravenously Experimental Treatment 1 Intervention

Subcutaneous portion of the study is complete. Dosing DF6002 Q4W

Group VI: Dose Escalation / Combination / Subcutaneously or Intravenously Experimental Treatment 2 Interventions

Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Dragonfly Therapeutics

Lead Sponsor

Trials

4

Recruited

1,300+

Findings from Research

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

In a phase II study involving 45 patients with MSI-H/dMMR metastatic colorectal cancer, the combination of nivolumab and low-dose ipilimumab showed a high objective response rate of 69% and a disease control rate of 84%, indicating strong efficacy as a first-line treatment.

The treatment was well tolerated, with only 22% of patients experiencing grade 3-4 treatment-related adverse events, and 74% of responders maintained their response at the time of data cutoff, suggesting durability of the treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. Lenz, HJ., Van Cutsem, E., Luisa Limon, M., 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 significantly improved one-year survival rates in patients with inoperable or metastatic BRAF V600-negative melanoma compared to dacarbazine (73% vs. 42%), indicating its efficacy as a first-line treatment option.

While nivolumab shows promise for treatment-naive patients, it does not demonstrate a clear advantage over other treatments for patients who have already received therapy, and it carries a risk of serious immunological side effects in 9% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab (OPDIVOO) BRAF V600 mutation-negative metastatic or inoperable melanoma: survival advantage. [2019]

Nivolumab, a monoclonal antibody targeting the programmed death receptor-1, has shown promising efficacy in treating advanced malignant melanoma, with nearly 25% of patients achieving a partial tumor response in a phase II trial involving previously treated stage III/IV patients.

The treatment demonstrated a durable clinical benefit, with a median progression-free survival of 172 days and an acceptable safety profile, as less than 18% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review of its use in patients with malignant melanoma. Deeks, ED.[2021]

References

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

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

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

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

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

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

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

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]

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

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

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

First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. [2022]

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

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. [2023]

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

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]

10. England pubmed.ncbi.nlm.nih.gov

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

11. France pubmed.ncbi.nlm.nih.gov

Nivolumab (OPDIVOO) BRAF V600 mutation-negative metastatic or inoperable melanoma: survival advantage. [2019]

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

Nivolumab: a review of its use in patients with malignant melanoma. [2021]