Study of DF6215 in Patients with Advanced Solid Tumors

NCT ID: NCT06108479

Last Updated: 2025-03-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

255 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-28

Study Completion Date

2027-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

A Phase I/Ib, First-In-Human, Multi-Part, Open-Label Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of DF6215 Monotherapy and in Combination Therapy in Patients with Advanced (Unresectable, Recurrent, or Metastatic) Solid Tumors; is designed to assess the safety, tolerability, and preliminary efficacy of DF6215 alone or in combination with pembrolizumab in patients with advanced solid tumors. The study is open-label, meaning both participants and investigators are aware of the treatment being administered.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This Phase I/Ib trial involves multiple parts and includes both dose-escalation and dose-expansion phases. The primary objectives are to evaluate the safety and tolerability of DF6215, an investigational biologic agent, when administered either as a monotherapy or in combination with pembrolizumab, a known immunotherapy drug, and evaluate the clinical activity of DF6215 monotherapy and in combination with pembrolizumab. Secondary objectives include assessing pharmacokinetics, pharmacodynamics, and preliminary efficacy based on tumor response using RECIST 1.1 criteria. The trial will enroll adult patients with advanced (unresectable, recurrent, or metastatic) solid tumors, and the study design allows for dose modifications based on safety monitoring and the occurrence of dose-limiting toxicities (DLTs). The trial will also incorporate a safety monitoring committee to review data at regular intervals to ensure patient safety .

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Solid Tumor, Adult Solid Tumor Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Monotherapy Dose Escalation

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

Group Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

Combination Therapy Dose Escalation

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

Group Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

pembrolizumab

Intervention Type DRUG

Anti-PD-1 immunotherapy agent

KEYTRUDA®

Intervention Type DRUG

Anti-PD-1 immunotherapy agent

Monotherapy Dose Enrichment

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 Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

Monotherapy Expansion of DF6215 in Advanced Melanoma

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 Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

Combination Expansion of DF6215 and pembrolizumab in PROC

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 Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

pembrolizumab

Intervention Type DRUG

Anti-PD-1 immunotherapy agent

KEYTRUDA®

Intervention Type DRUG

Anti-PD-1 immunotherapy agent

Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma

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.

Group Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

pembrolizumab

Intervention Type DRUG

Anti-PD-1 immunotherapy agent

KEYTRUDA®

Intervention Type DRUG

Anti-PD-1 immunotherapy agent

Monotherapy Expansion of DF6215 in Multiple Tumor Types (Basket)

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 Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types

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 Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

pembrolizumab

Intervention Type DRUG

Anti-PD-1 immunotherapy agent

KEYTRUDA®

Intervention Type DRUG

Anti-PD-1 immunotherapy agent

DF6215 Monotherapy Safety/PK/PD

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 Type EXPERIMENTAL

DF6215

Intervention Type DRUG

Immunotherapy (cytokine) targeting effector cells.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

DF6215

Immunotherapy (cytokine) targeting effector cells.

Intervention Type DRUG

pembrolizumab

Anti-PD-1 immunotherapy agent

Intervention Type DRUG

KEYTRUDA®

Anti-PD-1 immunotherapy agent

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Male or female patients ≥ 18 years old.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* An estimated life expectancy of ≥ 3 months.
* Adequate hematological function.
* Normal pulmonary function.
* Adequate hepatic function.
* Adequate renal function.
* Effective Contraception.

Exclusion Criteria

* Patients receiving chemotherapy, radiotherapy (other than palliative bone-directed radiotherapy), major surgery, or receiving another systemic anticancer therapeutic agent within 28 days before the start of study drug(s) or within 5 half-lives of the previous therapeutic agent (if known), whichever is shorter.
* Patients receiving any of the following concurrent anticancer treatments or investigational drugs within 28 days before the start of the study drug(s), or within 5 half-lives of the previous therapeutic agent (if known), whichever is shorter:

* Cytoreductive therapy
* Radiotherapy (except for palliative bone-directed radiotherapy)
* Note: ≤ 2 weeks of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study drug.
* Immune therapy
* Cytokine therapy (except for erythropoietin)
* Major surgery (excluding prior diagnostic biopsy)
* Concurrent systemic therapy with steroids or other immunosuppressive agents.
* Note that short-term administration of systemic steroids (eg, for allergic reactions or the management of irAEs) and physiologic dose steroids (≤ 10 mg prednisone, or equivalent) for those with treated brain metastases are allowed. Patients receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug(s) will be excluded.
* Bisphosphonate or denosumab initiated within 14 days of the first dose of study drug(s)
* Previous malignant disease, other than the target malignancies to be investigated in this study, within the last 3 years. Exceptions (eg, basal or squamous cell carcinoma of the skin, low grade prostate cancer \[Gleason score ≤ 6 and must be Stage I or II\], or cervical carcinoma in situ) may be considered on a case-by-case basis, in consultation with the Medical Monitor.
* Any of the following cardiac abnormalities:

* A clinically relevant abnormality on the electrocardiogram (ECG)
* Clinically relevant coronary artery disease (CAD) or uncontrolled congestive heart failure
* Medically uncontrolled angina pectoris
* An implantable pacemaker or automatic implantable cardioverter-defibrillator
* A history of risk factors for ventricular tachycardia, torsades de pointes, fainting, unexplained loss of consciousness, or convulsions
* A history of heart failure, congestive heart failure, cardiomyopathy, uncontrolled hypokalemia, hypomagnesemia, or hypoglycemia; any evidence of conduction abnormality (eg, increased QRS complex)
* Congenital long QT syndrome or a prolonged QTc mean on screening ECG
* QTc \> 470 msec for women and \> 450 msec for men
* History of myocardial infarction within 6 months before the first dose of study drug(s)
* Received sotalol within 10 days of the first dose of study drug(s), or received a medication known to prolong the ECG QT interval within 14 days of the first dose of study drug(s)
* A heart rate of \< 50 or \> 100 bpm at rest on screening ECG
* Patients aged more than 50 years must have a normal cardiac stress test.
* Patients with history of CAD must have a normal stress test (eg, thallium or technetium-99m sestamibi) and be cleared to participate in the study.
* History of ocular/uveal melanoma or mucosal melanoma.
* Primary tumor site of nasopharynx (any histology).
* Patients with brain metastases are excluded, unless all of the following criteria are met:

* CNS lesions are asymptomatic and previously treated
* Patient does not require ongoing daily steroid treatment for replacement for adrenal insufficiency (except ≤ 10 mg prednisone \[or equivalent\]) for at least 14 days before the first dose of study drug
* Imaging demonstrates stable disease 28 days after last treatment
* Receipt of any organ transplant, including autologous or allogeneic stem-cell transplantation.
* Patients must not have received aldesleukin or any other experimental IL-2 based drug, including intralesional administration.
* Significant acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV) infection during the screening window, as well as historic positive for human immunodeficiency virus (HIV) or clinically significant active infections that render the patient ineligible for study treatment as determined by the treating investigator.

* Patients with known HIV infection are excluded unless they meet the following criteria:
* Must have CD4+ T-cell (CD4+) counts ≥ 350 cells/μL at the time of screening, and
* Must have no history of AIDS-related opportunistic infections of HIV-associated conditions such as Kaposi sarcoma or multicentric Castleman's disease, and
* Patients on antiretroviral therapy (ART) must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening and agree to continue ART throughout the study
* Preexisting autoimmune disease (except vitiligo) needing treatment with systemic immunosuppressive agents for more than 28 days within the last 3 years, or clinically relevant immunodeficiencies (eg, dysgammaglobulinemia or congenital immunodeficiencies). Patients with a history of immune related endocrinopathies (eg, hypothyroidism, hyperthyroidism, and type 1 diabetes mellitus) that are stable on hormone replacement therapy are eligible for this study.
* Patients with a known medical history of keratitis, ulcerative keratitis, or corneal perforation.
* Patients with known history of neurologic conditions, cerebrovascular accident, or seizures.
* Known severe hypersensitivity reactions to mAbs (≥ Grade 3 as defined by NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly controlled asthma).
* Persisting toxicity related to a prior therapeutic agent \> Grade 1 as defined by NCI CTCAE v5.0 (however, ≤ Grade 2 alopecia, ≤ Grade 2 endocrinopathies, and ≤ Grade 2 sensory neuropathy are acceptable).
* Patients in certain cohorts with prior anti-PD-1 and anti-PD-L1 treatment are eligible for the study, unless they have experienced any of the following:

* Grade 3 or 4 treatment-related toxicity during an anti-PD-1 or anti-PD-L1 treatment (excluding Grade 3 or 4 immune-related endocrinopathies adequately controlled with hormone replacement therapy).
* Grade 2 treatment-related toxicity that impacted either the lungs, the nervous system, or the cardiac system, during an anti-PD-1 or anti-PD-L1 treatment (patients with a history of Grade 2 peripheral neuropathy, or paresthesia, not related to anti-PD-1 or anti-PD-L1 treatments are eligible).
* For combination basket cohorts: received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
* For combination basket cohorts: received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
* Known alcohol or drug abuse.
* Severe dyspnea at rest due to complications of advanced malignancy.
* Requiring supplementary oxygen therapy.
* All other significant diseases (eg, inflammatory bowel disease) which, in the opinion of the Investigator, might impair the patient's ability to participate.
* Legal incapacity or limited legal capacity.
* Unable to understand or give signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol. Examples include certain psychiatric conditions.
* Patients who have received a live or live-attenuated vaccine within 30 days before the first dose of study drug. Administration of killed vaccines is allowed.
* Pregnant or lactating.
* Severe hypersensitivity (≥ Grade 3) to study drugs and/or any of their excipients.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Dragonfly Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The Angeles Clinic and Research Institute - West Los Angeles Office

Los Angeles, California, United States

Site Status RECRUITING

University of California Irvine Medical Center

Orange, California, United States

Site Status RECRUITING

University of California San Diego Moores Cancer Center

San Diego, California, United States

Site Status RECRUITING

Sarcoma Oncology Center

Santa Monica, California, United States

Site Status RECRUITING

Tampa General Hospital

Tampa, Florida, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Lifespan - Rhode Island Hospital

Providence, Rhode Island, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

Cancer Research SA (CRSA)

Adelaide, South Australia, Australia

Site Status RECRUITING

Peninsula and South East Oncology Medical (PASO)

Frankston, Victoria, Australia

Site Status RECRUITING

Institut Bergonié

Bordeaux, , France

Site Status RECRUITING

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, , France

Site Status RECRUITING

Centre Georges François Leclerc

Dijon, , France

Site Status RECRUITING

CHU de Marseille - Hôpital de la Timone

Marseille, , France

Site Status RECRUITING

Institut Paoli-Calmettes

Marseille, , France

Site Status RECRUITING

Institut Curie

Paris, , France

Site Status RECRUITING

Hôpital Lyon-Sud

Pierre-Bénite, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Universitaire de Poitiers

Poitiers, , France

Site Status RECRUITING

Institut de Cancérologie de l'Ouest - Saint-Herblain - Site René Gauducheau

Saint-Herblain, , France

Site Status RECRUITING

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, , France

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States Australia France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Clinical Trials

Role: CONTACT

617-588-0086

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Navid Hafez, M.D., MPH

Role: primary

Jennifer Valerin, M.D., PhD

Role: primary

Gregory Daniels, M.D., PhD

Role: primary

Sant Chawla, M.D.

Role: primary

Mayer Fishman, M.D.

Role: primary

Ahmad Tarhini, M.D., PhD

Role: primary

Maya Dimitrova, M.D.

Role: primary

Benedito Carneiro, M.D.

Role: primary

Meredith McKean, M.D.

Role: primary

Sarwan Bishnoi, MBBS, MD, FRACP

Role: primary

Vinod Ganju, MBBS, FRACP

Role: primary

Antoine Italiano, M.D., PhD

Role: primary

Antoine Italiano, M.D., PhD

Role: primary

François Ghiringhelli, M.D., PhD

Role: primary

Caroline Gaudy, M.D., PhD

Role: primary

Cecile Vicier, M.D., PhD

Role: primary

Emanuela Romano, M.D., PhD

Role: primary

Benoit You, M.D., PhD

Role: primary

Nicolas Isambert, M.D.

Role: primary

Judith Raimbourg, M.D.

Role: primary

Iphigenie Korakis, M.D.

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

KEYNOTE-G13

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3475-G13

Identifier Type: OTHER

Identifier Source: secondary_id

DF6215-001

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors
NCT04478279 ACTIVE_NOT_RECRUITING PHASE1/PHASE2
Study to Evaluate D-1553 in Subjects With Solid Tumors
NCT04585035 ACTIVE_NOT_RECRUITING PHASE1/PHASE2