DF9001 + Nivolumab for Solid Tumors

Recruiting at 15 trial locations

Overseen By Sean Rossi

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dragonfly Therapeutics

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Autoimmune disease, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

242 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new molecule that helps the immune system attack cancer cells. It focuses on patients with solid tumors that have a protein called EGFR. The study will determine the best dose and test its effectiveness alone and with another drug called pembrolizumab. AM0010 has been previously tested in combination with pembrolizumab for advanced cancers.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy, radiotherapy, or major surgery within 28 days before starting the study treatment. You also cannot be on chronic systemic steroid therapy or other immunosuppressive therapy within 7 days prior to the first dose. It's best to discuss your specific medications with the trial team.

What data supports the idea that DF9001 + Nivolumab for Solid Tumors is an effective drug?

The available research shows that Nivolumab, a part of the DF9001 + Nivolumab combination, has been effective in treating several types of cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. It has been shown to help patients live longer in these conditions. However, there is no specific data provided about the effectiveness of the combination of DF9001 + Nivolumab for solid tumors in the information available. ^{1 2 3 4 5}

What safety data is available for DF9001 + Nivolumab treatment?

The safety data for Nivolumab, which is part of the DF9001 + Nivolumab treatment, indicates a manageable safety profile in various cancers, including advanced melanoma and non-small cell lung cancer (NSCLC). Nivolumab is associated with immune-related adverse events, which can be serious and potentially life-threatening, such as hematological toxicities and cutaneous toxicity. Long-term safety data, including 5-year follow-up, suggests that while Nivolumab has high antitumor activity, its immune-related adverse events may limit patient safety and therapy continuation. Efforts are ongoing to identify biomarkers to predict severe toxicity and to develop regimens with limited toxicity. ^{6 7 8 9 10}

Is the drug DF9001 a promising treatment for solid tumors?

DF9001 is being tested with nivolumab, a drug that helps the immune system fight cancer. Nivolumab has shown success in treating several types of cancer, like lung cancer and melanoma. This combination could be promising for treating solid tumors. ^{2 3 11 12 13}

Eligibility Criteria

Adults with various advanced solid tumors expressing EGFR, who have progressed after anti-PD-(L)1 therapy and other standard treatments. They must be able to undergo biopsies, have an ECOG status of 0 or 1, adequate organ function, and use effective contraception. Excluded are those with recent cancer therapies or surgeries, active infections like HIV/Hepatitis B/C, certain autoimmune diseases or severe allergies to monoclonal antibodies.

Inclusion Criteria

My liver is working well.

My cancer has worsened despite treatment for its advanced stage.

My colorectal cancer has returned or spread and tests show it has EGFR expression.

Exclusion Criteria

I have received an organ or stem cell transplant.

I do not have significant infections like HIV or active hepatitis.

I have a medical history that may increase my risk of side effects from EGFR treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive DF9001 in sequential ascending doses to determine the recommended phase 1b dose

4 weeks

Dose Expansion

Participants receive the recommended phase 1b dose of DF9001, either as monotherapy or in combination with pembrolizumab

Variable, based on cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after last treatment

Long-term Follow-up

Participants are assessed for overall response rate and progression-free survival

Up to 24 months

Treatment Details

Interventions

• DF9001
• Nivolumab

Trial Overview The trial is testing DF9001 alone and in combination with Nivolumab on patients with solid tumors that express EGFR. It has two phases: dose escalation to find the best dose of DF9001 and expansion where this dose is given to more people. The goal is to activate NK cells and T-cells against cancer.

Participant Groups

Group I: Monotherapy DF9001 Expansion in Renal Cell Carcinoma Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20-40 patients with renal cell carcinoma (RCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Group II: Monotherapy DF9001 Expansion in Non-small Cell Lung Cancer Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20-40 patients with Non-small cell lung cancer (NSCLC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Group III: Monotherapy DF9001 Expansion in Head and Neck Squamous Cell Carcinoma Experimental Treatment 1 Intervention

Monotherapy expansion cohort enrolling up to 20-40 patients with head and neck squamous cell carcinoma (HNSCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Group IV: Monotherapy DF9001 Dose Escalation Experimental Treatment 1 Intervention

Dose escalation cohorts of DF9001 in sequential ascending order.

Group V: Combination Expansion of DF9001 and pembrolizumab in Renal Cell Carcinoma Experimental Treatment 2 Interventions

Combination expansion cohort using DF9001 and a PD-1 checkpoint inhibitor enrolling 20-40 patients with renal cell carcinoma (RCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Group VI: Combination Expansion of DF9001 and pembrolizumab in Head and Neck Squamous Cell Carcinoma Experimental Treatment 2 Interventions

Combination expansion cohort using DF9001 and a PD-1 checkpoint inhibitor enrolling 20-40 patients with head and neck squamous cell carcinoma (HNSCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Who Is Running the Clinical Trial?

Dragonfly Therapeutics

Lead Sponsor

Trials

4

Recruited

1,300+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Nivolumab is shown to be the most cost-effective treatment option for advanced melanoma patients in England, with incremental cost-effectiveness ratios of £24,483 for BRAF mutation-negative and £17,362 for mutation-positive patients.

The analysis utilized a Markov state-transition model based on patient-level data from clinical trials, indicating that nivolumab provides long-term survival benefits while being economically favorable compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

Nivolumab is an effective immune checkpoint inhibitor for treating various cancers, including melanoma and non-small-cell lung cancer, and its efficacy may be linked to the expression of PD-L1 in tumors.

In comparing two antibodies for detecting PD-L1, the 28-8 antibody showed superior detection capabilities over E1L3N, highlighting the importance of antibody choice and detection methods in assessing PD-L1 expression for predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Analytical Comparison of Dako 28-8 PharmDx Assay and an E1L3N Laboratory-Developed Test in the Immunohistochemical Detection of Programmed Death-Ligand 1. Cogswell, J., Inzunza, HD., Wu, Q., et al.[2021]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab shows similar efficacy in treating advanced melanoma for patients with wild-type BRAF (34.6% response rate) compared to those with mutant BRAF (29.7% response rate), based on a retrospective analysis of 440 patients from four clinical trials.

The safety profile of nivolumab is comparable between the two groups, with treatment-related adverse events occurring in 68.3% of wild-type BRAF patients and 58.5% of mutant BRAF patients, indicating that nivolumab is a viable treatment option regardless of BRAF mutation status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nivolumab in Patients With BRAF V600 Mutant and BRAF Wild-Type Advanced Melanoma: A Pooled Analysis of 4 Clinical Trials. Larkin, J., Lao, CD., Urba, WJ., et al.[2022]

Nivolumab is the first approved PD-1 inhibitor that helps the immune system fight against tumors, specifically for patients with unresectable melanoma.

Early phase studies have shown promising results for nivolumab in treating solid tumors like non-small cell lung cancer (NSCLC), especially when combined with chemotherapy and other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in NSCLC: latest evidence and clinical potential. Sundar, R., Cho, BC., Brahmer, JR., et al.[2022]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

The combination of nivolumab and relatlimab shows a manageable safety profile for patients with advanced melanoma who have already undergone treatment.

This combination therapy may offer a new option for patients with pretreated melanoma, suggesting potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

A 62-year-old male with metastatic squamous cell lung cancer experienced grade 2 cutaneous toxicity after treatment with nivolumab, yet maintained a durable partial response for over a year after discontinuing the drug.

The development of immune-related skin toxicities during nivolumab treatment may indicate a better clinical outcome, suggesting that in some cases, it might be reasonable to suspend treatment and monitor the patient closely instead of resuming therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term response control in a patient with metastatic squamous cell lung cancer after treatment with nivolumab: a case report. Pampín-Sánchez, R., Barbazán-Vázquez, FJ., Fernández-González, B., et al.[2022]

In a multicenter phase II study involving 76 Japanese patients with advanced non-squamous NSCLC, nivolumab demonstrated a 22.4% overall response rate, indicating its efficacy after platinum-based chemotherapy.

Nivolumab was well tolerated, with serious treatment-related adverse events occurring in 17 patients, but these were manageable, and the treatment showed better responses in current/former smokers and patients with wild type/unknown EGFR mutation status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre phase II study of nivolumab in Japanese patients with advanced or recurrent non-squamous non-small cell lung cancer. Nishio, M., Hida, T., Atagi, S., et al.[2022]

Nivolumab, an immune checkpoint inhibitor targeting PD-1, shows promise for imaging PD-1-expressing T-cells in tumors using a radiolabeled tracer (89Zr-Df-nivolumab), which was validated in a humanized mouse model of lung cancer.

The PET imaging results demonstrated clear visualization of tumors and T-cell infiltration in salivary glands, suggesting that PD-1-targeted imaging could enhance the development of immunotherapies and improve diagnostics and monitoring in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer. England, CG., Jiang, D., Ehlerding, EB., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, was administered to two advanced non-small cell lung cancer (NSCLC) patients for 5 and 9 months, respectively, and both showed a durable response even after discontinuation of the treatment due to socioeconomic reasons.

The patients maintained their clinical and radiologic responses after stopping nivolumab without experiencing disease progression or toxicity, suggesting that some patients may sustain benefits from immunotherapy even after treatment cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable response after discontinuation of nivolumab therapy in the absence of disease progression or toxicity with two advanced NSCLC patients. Yilmaz, M., Guven Mese, S.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]

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

An Analytical Comparison of Dako 28-8 PharmDx Assay and an E1L3N Laboratory-Developed Test in the Immunohistochemical Detection of Programmed Death-Ligand 1. [2021]

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

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. [2018]

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

Efficacy and Safety of Nivolumab in Patients With BRAF V600 Mutant and BRAF Wild-Type Advanced Melanoma: A Pooled Analysis of 4 Clinical Trials. [2022]

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

Nivolumab in NSCLC: latest evidence and clinical potential. [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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

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

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

9. England pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]

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

Long-term response control in a patient with metastatic squamous cell lung cancer after treatment with nivolumab: a case report. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Multicentre phase II study of nivolumab in Japanese patients with advanced or recurrent non-squamous non-small cell lung cancer. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

89Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Durable response after discontinuation of nivolumab therapy in the absence of disease progression or toxicity with two advanced NSCLC patients. [2022]