A Study of DF6002 Alone and in Combination With Nivolumab

A Phase 1/1b, First-In-Human, Multi-Part, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF6002 as a Monotherapy and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications

The purpose of this study is to evaluate the safety, tolerability, drug-levels, drug-effects and preliminary anti-tumor activity of DF6002 alone and in combination with Nivolumab in participants with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Nivolumab; Drug: DF6002

Detailed Description

Assess the safety and tolerability of subcutaneous (SC) and intravenous (IV) administration of DF6002, as monotherapy and in combination with nivolumab, and to determine the maximum tolerated dose (MTD) and recommended efficacy expansion dose (REED) of SC and IV DF6002, both as monotherapy and in combination with nivolumab, for patients with advanced (unresectable, recurrent, or metastatic) solid tumors.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Local Institution - 0023
  • Heidelberg, Australia, 3084
    • Local Institution - 0022
• France
  • Bordeaux, France, 33000
    • Institut Bergonie
  • Paris, France, 75010
    • Hôpital Saint-Louis
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon-Sud
  • Villejuif, France, 94805
    • Gustave Roussy
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28027
    • Clínica Universidad de Navarra - Madrid
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • START Madrid - Hospital Universitario Fundacion Jimenez Diaz
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra - Pamplona
• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine
  • Colorado
    • Denver, Colorado, United States, 80218
      • SCRI - HealthOne Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale School of Medicine
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Augusta, Georgia, United States, 30912-0003
      • Augusta University Georgia Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • HealthPartners Cancer Center at regions Hospital
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • SCRI - Tennessee Oncology - Saint Thomas West Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute and Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • USOR - Virginia Cancer Specialists - Fairfax Office
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Advanced/metastatic solid tumors, for which no standard therapy exists or standard therapy has failed among the following tumor types: melanoma, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell, urothelial, gastric, esophageal, cervical, hepatocellular, merkel cell, cutaneous squamous cell carcinoma, renal cell, endometrial, triple-negative breast, ovarian, and prostate
• ECOG performance status of 0 or 1
• Clinical or radiological evidence of disease
• Adequate hematological, hepatic and renal function
• Anticoagulants are required for the following: Khorana Risk Score ≥ 2 or as assessed by Investigator as being at high risk for venous thromboembolism (VTE) or history of VTE ≥ 6 months from enrollment

Exclusion Criteria:

• Concurrent anticancer treatment (with the exception of palliative bone directed radiotherapy), immune therapy, or cytokine therapy (except for erythropoietin), major surgery (excluding prior diagnostic biopsy), concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of study treatment
• Prior treatment with DF6002, recombinant human interleukin-12 (rhIL-12)-directed therapy, or any drug containing an interleukin-12 (IL-12) moiety
• Previous malignant disease other than the current target malignancy within the last 3 years, with the exception of basal or squamous cell carcinoma of the skin, localized prostate cancer or cervical carcinoma in situ
• Rapidly progressive disease
• Serious cardiac illness or medical conditions
• Known diagnosis of antiphospholipid syndrome or clinically significant hereditary thrombophilia

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation / Monotherapy / Subcutaneously or Intravenously; Subcutaneous portion of the study is complete. Dosing DF6002 Q4W	Drug: DF6002; Specified dose on specified days; Other Names: BMS-986415
Experimental: Dose Escalation / Combination / Subcutaneously or Intravenously; Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W	Drug: Nivolumab; Specified dose on specified days; Other Names: Opdivo; Drug: DF6002; Specified dose on specified days; Other Names: BMS-986415
Experimental: Safety/PK/PD / Monotherapy / Subcutaneously or Intravenously; Subcutaneous portion of the study is complete. Dosing DF6002 Q4W	Drug: DF6002; Specified dose on specified days; Other Names: BMS-986415
Experimental: Safety/PK/PD / Combination / Subcutaneously or Intravenously; Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W	Drug: Nivolumab; Specified dose on specified days; Other Names: Opdivo; Drug: DF6002; Specified dose on specified days; Other Names: BMS-986415
Experimental: Efficacy Expansion / Combination / Subcutaneously or Intravenously / Melanoma; Subcutaneous portion of the study is complete. 2L+ melanoma Dosing DF6002 Q4W Dosing nivolumab Q4W	Drug: Nivolumab; Specified dose on specified days; Other Names: Opdivo; Drug: DF6002; Specified dose on specified days; Other Names: BMS-986415
Experimental: Efficacy Expansion / Combination / Subcutaneously or Intravenously / Non-Melanoma; Subcutaneous portion of the study is complete. 2L+ non-melanoma skin cancer (including cSCC, BCC, and MCC) Dosing DF6002 Q4W Dosing nivolumab Q4W	Drug: Nivolumab; Specified dose on specified days; Other Names: Opdivo; Drug: DF6002; Specified dose on specified days; Other Names: BMS-986415

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with dose-limiting toxicities (DLTs)	Dose Escalation	During the first 3 weeks of treatment
Overall Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per an Independent Endpoint Review Committee (IERC)	Efficacy Expansion Arms	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed ORR per RECIST 1.1 per Investigator assessment	Phase 1/1b only	Up to 2 years
Progression-free survival (PFS) according to RECIST 1.1 per Investigator assessment	Phase 2 only	Up to 2 years
CBR according to RECIST 1.1 per IERC	Phase 2 only	Up to 2 years
PFS according to RECIST 1.1 per IERC	Phase 2 only	Up to 2 years
DOR according to RECIST 1.1 per IERC	Phase 2 only	Up to month 24
Unconfirmed response after 4 cycles according to RECIST 1.1	Phase 2 only	Up to 2 years
Overall Survival (OS)	Phase 2 only	Up to 5 years
Serum titers of anti-DF6002 antibodies	Phase 2 only	Up to 2 years
Serum titers of anti-nivolumab antibodies	Phase 2 only	Up to 2 years
Amount of Treatment Emergent Adverse Events (TEAEs)	Number of participants with TEAEs	Up to 2 years
Severity of TEAEs	Severity of the TEAEs seen in study participants	Up to 2 years
Duration of TEAEs	How long the TEAEs seen last	Up to 2 years
Number of participants with changes from baseline in clinical laboratory parameters	Overall change, if any, after treatment	Up to 2 years
Number of participants with changes from baseline in electrocardiogram (ECG) parameters	Overall change, if any, after treatment	Up to 2 years
Number of participants with changes from baseline in vital sign parameters	Overall change, if any, after treatment	Up to 2 years
Duration of Response (DOR) according to RECIST 1.1 per Investigator assessment	Overall change, if any, after treatment	Up to month 24
Area under the plasma concentration-time curve from the time of dosing to the time of the last observation (AUC 0-T)	Overall change, if any, after treatment	Up to day 28
Area under the plasma concentration-time curve from the time of dosing extrapolated to infinity (AUC 0-INF)	Overall change, if any, after treatment	Up to day 28
Maximum serum concentration observed post-dose (Cmax)	Overall change, if any, after treatment	Up to day 28
Best overall response (BOR) according to RECIST 1.1 per Investigator assessment	Overall change, if any, after treatment	Approximately one year
Clinical benefit rate (CBR) according to RECIST 1.1 per Investigator assessment	Overall change, if any, after treatment	Up to 2 years

Collaborators and Investigators

• Sponsor: Dragonfly Therapeutics
• Investigators: Study Chair: Clinical Trials, Dragonfly Therapeutics

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2020
• Primary Completion (Actual): November 26, 2025
• Study Completion (Actual): November 26, 2025

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Melanoma; Non-small Cell Lung Cancer; Advanced or Metastatic Solid Tumors; DF6002
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Non-Small-Cell Lung; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: DF6002 - 001; 2023-510511-19 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No