DF6215 for Solid Tumors

Recruiting at 23 trial locations

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dragonfly Therapeutics

Must not be taking: Chemotherapy, Radiotherapy, Immunosuppressants, others

Disqualifiers: Brain metastases, Organ transplant, others

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

Compensation: Varies

Number of Visits: 30

255 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DF6215 (a modified interleukin-2 therapy), either alone or with pembrolizumab, to determine its safety and effectiveness for people with advanced solid tumors that are inoperable, recurrent, or metastatic. The trial is open-label, so participants and doctors will know which treatment is administered. It seeks patients with conditions like advanced melanoma or platinum-resistant ovarian cancer who have previously tried other treatments. Individuals with solid tumors who meet specific health criteria, such as normal heart and lung function, may qualify for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as chemotherapy, radiotherapy, or other anticancer treatments, at least 28 days before starting the study drug. However, you can continue taking bisphosphonate or denosumab if started at least 14 days before the trial.

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

Research shows that DF6215, when used alone, may be less harmful than traditional treatments. Studies have found that a modified version of interleukin-2, a component of DF6215, can effectively treat cancers like melanoma and kidney cancer with fewer side effects, making it potentially easier for patients to handle.

When DF6215 is combined with pembrolizumab, research has assessed its safety. Previous studies aimed to demonstrate that the side effects of combining interleukin-2 with pembrolizumab are manageable, suggesting that even in combination, DF6215 might be tolerable for patients.

As this is an early-phase study, the primary focus is on assessing the safety and tolerability of DF6215, either alone or with pembrolizumab. Although data may be limited, initial findings support its potential safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

DF6215 is unique because it targets solid tumors in a novel way, potentially enhancing the effectiveness of existing treatments like pembrolizumab. Unlike standard treatments, which typically focus on established pathways, DF6215 can be used both as a standalone therapy and in combination with pembrolizumab to potentially boost its efficacy. Researchers are excited about DF6215 because it offers a fresh approach by exploring different dose levels and combinations to determine the most effective and safe treatment strategy for patients with various tumor types, including advanced melanoma and platinum-resistant ovarian cancer. This flexibility and potential synergy with other treatments may lead to improved outcomes for patients who have limited options.

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

Research has shown that DF6215 is promising in early studies for treating solid tumors. This treatment helps the immune system better identify and attack cancer cells. Initial results suggest DF6215 might offer benefits without causing severe side effects like capillary leak syndrome. In this trial, some participants will receive DF6215 alone, while others will receive it in combination with pembrolizumab. Pembrolizumab, already effective against many solid tumors, has demonstrated high rates of remission and survival. The combination aims to enhance the overall treatment effect, increasing the benefits of both treatments. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced solid tumors where standard treatments have failed or don't exist. They should be relatively healthy (ECOG status of 0 or 1) and expected to live at least another three months. Participants need good blood and heart function, and must use effective birth control.

Inclusion Criteria

My blood counts are within a healthy range.

My heart is functioning well.

I am mostly active and my doctor thinks I have at least 3 months to live.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive DF6215 in sequential ascending doses to evaluate safety and determine the optimal dose

4 weeks

Weekly visits for dose escalation

Dose Expansion

Participants receive the best dose selected from the dose escalation phase to further evaluate safety and efficacy

Up to 24 months

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days

Follow-up visits every 30 days

What Are the Treatments Tested in This Trial?

Interventions

• DF6215

Trial Overview

The study tests DF6215, a modified cytokine aimed at boosting the immune system's ability to fight cancer. It has two parts: first, finding the right dose; second, expanding that dose to more patients with specific types of solid tumors.

How Is the Trial Designed?

Group I: Monotherapy Expansion of DF6215 in Multiple Tumor Types (Basket) Experimental Treatment 1 Intervention

Patients with multiple tumor types will receive DF6215 monotherapy at the recommended efficacy expansion dose to evaluate the clinical activity of DF6215 in monotherapy.

Group II: Monotherapy Expansion of DF6215 in Advanced Melanoma Experimental Treatment 1 Intervention

Patients with advanced melanoma after prior anti-PD-1 will receive DF6215 monotherapy at the recommended efficacy expansion dose to evaluate the clinical activity of DF6215 in monotherapy.

Group III: Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Patients will receive DF6215 monotherapy, with dose levels escalated to determine the MTD of DF6215 monotherapy.

Group IV: Monotherapy Dose Enrichment Experimental Treatment 1 Intervention

Patients with advanced melanoma after prior anti-PD-1 treatment will receive DF6215 monotherapy at two different dose levels to further characterize the doses selected during the Dose Escalation (monotherapy) part.

Group V: DF6215 Monotherapy Safety/PK/PD Experimental Treatment 1 Intervention

Expansion cohorts of DF6215 in multiple dose levels after evaluation for safety in the DF6215 Dose Escalation arm. Additional Pharmacokinetic (PK) and Pharmacodynamic (PD) samples included in this arm.

Group VI: Combination Therapy Dose Escalation Experimental Treatment 3 Interventions

Patients will receive DF6215 in combination with pembrolizumab to determine the MTD of DF6215 in combination with pembrolizumab.

Group VII: Combination Expansion of DF6215 and pembrolizumab in PROC Experimental Treatment 3 Interventions

Patients with platinum-resistant ovarian cancer (PROC) will receive DF6215 in combination with pembrolizumab at the recommended efficacy expansion dose to evaluate the clinical activity of DF6215 in combination with pembrolizumab.

Group VIII: Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types Experimental Treatment 3 Interventions

Patients with multiple tumor types will receive DF6215 in combination with pembrolizumab at the recommended combination efficacy expansion dose to evaluate the clinical activity of DF6215 in combination with pembrolizumab.

Group IX: Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma Experimental Treatment 3 Interventions

Patients with advanced melanoma after prior anti-PD-1 therapy will receive DF6215 in combination with pembrolizumab at the recommended combination efficacy expansion dose to evaluate the clinical activity of DF6215 in combination with pembrolizumab.

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

Published Research Related to This Trial

The 'BALLkine-2' nanoparticle formulation of recombinant human IL-2 significantly reduces systemic side effects and toxicity associated with high-dose IL-2 treatment, as demonstrated in cynomolgus monkeys.

This innovative delivery method enhances the effectiveness of IL-2 by increasing its half-life and promoting intratumoral lymphocyte infiltration without increasing regulatory T cell development, making it a promising option for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle delivery of recombinant IL-2 (BALLkine-2) achieves durable tumor control with less systemic adverse effects in cancer immunotherapy. Kim, J., Kang, S., Kim, KW., et al.[2022]

A novel human IL-2 mutant has been developed that shows higher antitumor efficacy and lower toxicity compared to wild type IL-2, making it a promising candidate for cancer therapy.

This mutant selectively promotes the proliferation of immune cells that fight tumors while reducing the expansion of regulatory T cells, which can suppress antitumor immunity, thus enhancing its effectiveness in various tumor models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human IL-2 mutein with higher antitumor efficacy than wild type IL-2. Carmenate, T., Pacios, A., Enamorado, M., et al.[2020]

Denileukin Diftitox (DD), a fusion protein that targets IL-2 receptors on tumor cells, has shown a 36.1% objective response rate in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), indicating comparable efficacy to existing therapies.

E7777, the improved formulation of DD, has a maximum tolerated dose of 9 μg/kg/day and is associated with a high incidence of grade 3 or higher adverse events (94.6%), necessitating ongoing safety monitoring, especially for serious conditions like capillary leak syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preclinical and clinical researches of Denileukin Diftitox (Genetical Recombination) (Remitoro®), a novel agent for T-cell lymphoma]. Shiiba, H., Takechi, A., Asakura, S., et al.[2022]

BAY 50-4798, a modified version of human IL-2, shows approximately 3,000-fold selectivity for T cells over NK cells, potentially reducing the severe toxicity associated with traditional IL-2 therapy.

In studies with chimpanzees, BAY 50-4798 demonstrated comparable T-cell activation to human IL-2 but was better tolerated, and it also inhibited metastasis in mouse tumor models, suggesting it may be a safer and more effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A T-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo. Shanafelt, AB., Lin, Y., Shanafelt, MC., et al.[2021]

The engineered mutant IL2 (IL2v) shows reduced binding to the high-affinity IL2 receptor compared to wild-type IL2 (wt-IL2), resulting in lower toxicity and a longer plasma half-life, making it a safer option for therapy.

PET studies demonstrated that IL2v has a significantly lower volume of distribution and binding potential in activated immune cells compared to wt-IL2, indicating that IL2v may be more suitable for therapeutic use due to its reduced receptor binding and slower kinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic properties of radiolabeled mutant Interleukin-2v: a PET imaging study. Hartimath, SV., Manuelli, V., Zijlma, R., et al.[2019]

High-dose interleukin-2 (IL-2) has been used to treat certain cancers, but its clinical use is limited due to a short half-life and significant toxicity.

Recent advancements in engineered IL-2 mutants aim to selectively stimulate beneficial T cells while reducing harmful side effects, enhancing their potential for cancer treatment and autoimmune disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic strategies based on biasing IL-2 mutants for cancers and autoimmune diseases. Jin, D., Jiang, Y., Chang, L., et al.[2022]

High-dose recombinant human IL-2 (rhIL-2) has shown potential as a treatment for metastatic melanoma and renal cell carcinoma, leading to durable antitumor responses in some patients, but its use is limited due to severe side effects that require specialized medical support.

Recent advancements in drug development, including engineered IL-2 variants, aim to enhance the efficacy and safety of IL-2 therapies by selectively activating anti-tumor immune cells, potentially expanding its use beyond current FDA-approved indications and allowing for safer combinations with other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rethinking Oncologic Treatment Strategies with Interleukin-2. Ko, B., Takebe, N., Andrews, O., et al.[2023]

Interleukin-2 (IL-2) therapy shows promise in treating tumors, particularly when administered at lower tumor burdens, as predicted by preclinical studies, highlighting the importance of tumor susceptibility and host factors in treatment efficacy.

Combining IL-2 with other cytokines or activated immune cells enhances its antitumor effects, suggesting that optimizing dosage, scheduling, and combination therapies could lead to more effective and less toxic cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons from the clinical trials of interleukin-2. Parkinson, DR.[2007]

High-dose interleukin-2 (HD IL-2) treatment in patients with metastatic renal cell cancer (RCC) resulted in a median survival of 18 months and a 1-year survival rate of 74%, compared to 14 months and 51% for other cytokine therapies.

The study, which reviewed data from 85 patients with a median follow-up of 13 months, indicates that HD IL-2 provides a clinically meaningful improvement in survival outcomes for metastatic RCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of therapy choice on overall survival in metastatic renal cell carcinoma: a single institution experience. Parmar, S., Rademaker, AW., Fung, BB., et al.[2022]

A mutated form of human interleukin-2 (IL-2) was developed to have a reduced affinity for the high-affinity IL-2 receptor alpha (IL-2Rα), which is responsible for severe toxicity in cancer treatments.

This mutant IL-2 demonstrated higher antitumor activity and better cytotoxic effects compared to the wild type IL-2, suggesting it could be a safer and more effective option for immunotherapy in cancers like melanoma and renal cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and antitumor activity of a mutant type of interleukin 2. Dehghan, R., Beig Parikhani, A., Zeinali, S., et al.[2022]

Denileukin diftitox demonstrated significant efficacy in treating relapsed/refractory T-cell non-Hodgkin lymphoma, with an objective response rate of 48.1% among 27 patients, including complete responses in six patients and partial responses in seven patients.

The treatment was well tolerated, with most adverse reactions being mild (grade 1/2) and no severe (grade 4-5) toxicities reported, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma. Dang, NH., Pro, B., Hagemeister, FB., et al.[2013]

The modified IL-2 variant, IL-2K35C-moFA, effectively activates tumor-killing CD8+ T cells and NK cells while reducing the amplification of regulatory T cells (Tregs), addressing limitations of traditional IL-2 therapy.

In a murine tumor model, IL-2K35C-moFA demonstrated significant efficacy as a single dose, providing durable immunity for one week, suggesting its potential as a novel cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-2K35C-moFA, a Long-Acting Engineered Cytokine with Decreased Interleukin 2 Receptor α Binding, Improved the Cellular Selectivity Profile and Antitumor Efficacy in a Mouse Tumor Model. Wang, X., Chen, G., Nie, L., et al.[2022]

The intravenous administration of DAB486-IL-2 has demonstrated the feasibility of fusion toxin therapy in patients with refractory hematological malignancies, indicating a promising new treatment approach.

The development of receptor-targeted fusion toxins, such as DAB389-EGF for breast cancer and DAB389-IL-7 for acute leukemias, suggests that this method could be adapted for various cancers by targeting specific cell-surface receptors associated with disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diphtheria toxin-based receptor-specific chimaeric toxins as targeted therapies. Sweeney, EB., Murphy, JR.[2005]

Citations

1.

clinicaltrials.ucsd.edu

clinicaltrials.ucsd.edu/trial/NCT06108479

Study of DF6215 in Patients with Advanced Solid Tumors

A Phase I/Ib, First-In-Human, Multi-Part, Open-Label Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of DF6215

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withpower.com

withpower.com/trial/phase-1-neoplasms-10-2023-44a3a

DF6215 for Solid Tumors

This trial tests a modified protein that helps the immune system fight cancer in patients with solid tumors by making it easier for immune cells to find and ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2704

A phase 1/1b, first-in-human, multi-part study of DF6215 ...

Methods: This is a first-in-human, open-label, multipart, Phase 1/1b clinical trial to characterize the initial safety, tolerability, ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12521426/

Efficacy and safety of pembrolizumab for the treatment of ...

Pembrolizumab has demonstrated high objective remission and overall survival rates in a variety of solid tumors, and clinical trials are now ...

5.

cancernetwork.com

cancernetwork.com/view/nemvaleukin-pembrolizumab-yield-no-os-improvement-in-ovarian-cancer

Nemvaleukin/Pembrolizumab Yield No OS Improvement in ...

Nemvaleukin alfa, an engineered interleukin-2 (IL-2) variant immunotherapy, plus pembrolizumab (Keytruda) did not elicit a significant improvement in overall ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06108479

Study of DF6215 in Patients with Advanced Solid Tumors

The primary objectives are to evaluate the safety and tolerability of DF6215, an investigational biologic agent, when administered either as a monotherapy or in ...

7.

kidneycancer.org

kidneycancer.org/trial/study-of-df6215-in-patients-with-advanced-solid-tumors/

Study of DF6215 in Patients With Advanced Solid Tumors

Brief Summary. DF6215-001 is a study of a modified human cytokine (interleukin-2; IL-2) that retains the ability to bind to a certain part of the IL-2 ...