DF9001 + Nivolumab for Solid Tumors

No longer recruiting at 16 trial locations
SR
Overseen BySean Rossi
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DF9001, which activates specific immune cells to target cancer cells. The study targets individuals with certain solid tumors that express a protein called EGFR. It includes two phases: the first determines the optimal dose, and the second tests that dose in various cancers, such as renal cell carcinoma and head and neck cancer. Eligible participants include those with EGFR-positive tumors who have experienced cancer progression despite previous treatments. As a Phase 1 and Phase 2 trial, this research aims to understand how DF9001 works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the safety of DF9001, a new treatment targeting cancer cells, remains under investigation. This treatment undergoes testing both alone and in combination with pembrolizumab, a drug already approved for cancer. Unfortunately, limited information exists on how well individuals tolerate DF9001 alone or with pembrolizumab.

The trial is in its early stages, so scientists are still gathering data on its safety in humans. These early trials aim to determine the treatment's safety and potential side effects. Since the treatment is still under evaluation, participants should be aware that its safety is not yet fully understood.

Pembrolizumab, when used alone, is an approved treatment for some cancers and is generally well-tolerated. However, combining it with DF9001 is new, so the safety of this combination remains uncertain. Prospective participants should consult their doctor to understand the implications of joining this clinical trial.12345

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cancers like renal cell carcinoma, head and neck squamous cell carcinoma, and non-small cell lung cancer, which typically involve surgery, radiation, and various chemotherapy drugs, DF9001 offers a novel approach as an experimental therapy. DF9001 is designed to be used both alone and in combination with checkpoint inhibitors like pembrolizumab. This combination aims to enhance the body's immune response against tumors more effectively. By targeting specific pathways in the immune system, DF9001 could potentially offer improved outcomes with fewer side effects compared to traditional treatments. Researchers are excited about DF9001 because it represents a new class of treatment that may unlock more personalized and effective cancer care.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that DF9001 helps fight cancer by boosting the activity of natural killer and T-cells, key components of the immune system. This approach aims to halt tumor growth and enhance the body's cancer-fighting ability. Early studies found DF9001 more effective at combating tumors than cetuximab, a common treatment, because it targets EGFR, a protein on some cancer cells. In this trial, researchers are testing DF9001 combined with pembrolizumab for kidney cancer (Renal Cell Carcinoma) and certain head and neck cancers (Head and Neck Squamous Cell Carcinoma). Another similar drug, nivolumab, has successfully treated these cancers by slowing tumor growth and extending patient survival. These findings suggest that DF9001, whether used alone or with other treatments, could benefit certain cancer types.12367

Are You a Good Fit for This Trial?

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.
See 21 more

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.
See 15 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
6Treatment groups
Experimental Treatment
Group I: Monotherapy DF9001 Expansion in Renal Cell CarcinomaExperimental Treatment1 Intervention
Group II: Monotherapy DF9001 Expansion in Non-small Cell Lung CancerExperimental Treatment1 Intervention
Group III: Monotherapy DF9001 Expansion in Head and Neck Squamous Cell CarcinomaExperimental Treatment1 Intervention
Group IV: Monotherapy DF9001 Dose EscalationExperimental Treatment1 Intervention
Group V: Combination Expansion of DF9001 and pembrolizumab in Renal Cell CarcinomaExperimental Treatment2 Interventions
Group VI: Combination Expansion of DF9001 and pembrolizumab in Head and Neck Squamous Cell CarcinomaExperimental Treatment2 Interventions

Find a Clinic Near You

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 profile image

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 profile image

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

Published Research Related to This Trial

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.
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]
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.
The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis.Shi, Z., Liu, X., Chen, M., et al.[2023]
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.
An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers.Wong, AC., Ma, B.[2018]

Citations

Study of DF9001 in Patients With Advanced Solid TumorsDF9001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells.
Study to evaluate DF9001 plus pembrolizumab in solid ...DF9001 is an EGFR immune engager that is currently being investigated as a monotherapy in patients with RCC, head and neck squamous cell ...
Review of Current and Future Medical Treatments in Head ...Here, we provide a review of how medical therapy is used in the management of HNSCC, with a specific focus on active clinical trials.
Flamingo doses first subject in Phase II head and neck ...Flamingo Therapeutics has dosed the first subject in the Phase II trial of danvatirsen regimen for head and neck squamous cell carcinoma.
(PDF) 1060 DF9001, an EGFR targeted immune engager ...Conclusions DF9001 disrupts tumor growth by inhibiting EGFR signaling and promoting anti-tumor immunity. DF9001 has been optimized for ...
MSD's trial of cancer treatment meets primary endpointMSD has reported that the Phase III KEYNOTE-689 trial of KEYTRUDA to treat head and neck squamous cell carcinoma met the primary endpoint.
Merck's KEYTRUDA® (pembrolizumab) Met Primary ...KEYNOTE-689 is the first Phase 3 trial to demonstrate statistically significant and clinically meaningful improvement in EFS in the intent-to-treat population.
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