A Study of DF6002 Alone and in Combination With Nivolumab
- Registration Number
- NCT04423029
- Lead Sponsor
- Dragonfly Therapeutics
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 438
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Escalation / Monotherapy / Subcutaneously or Intravenously DF6002 Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dose Escalation / Combination / Subcutaneously or Intravenously DF6002 Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W Dose Escalation / Combination / Subcutaneously or Intravenously Nivolumab Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W Safety/PK/PD / Combination / Subcutaneously or Intravenously Nivolumab Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W Efficacy Expansion / Combination / Subcutaneously or Intravenously / Melanoma Nivolumab Subcutaneous portion of the study is complete. 2L+ melanoma Dosing DF6002 Q4W Dosing nivolumab Q4W Efficacy Expansion / Combination / Subcutaneously or Intravenously / Non-Melanoma Nivolumab Subcutaneous portion of the study is complete. 2L+ non-melanoma skin cancer (including cSCC, BCC, and MCC) Dosing DF6002 Q4W Dosing nivolumab Q4W Safety/PK/PD / Monotherapy / Subcutaneously or Intravenously DF6002 Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Safety/PK/PD / Combination / Subcutaneously or Intravenously DF6002 Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W Efficacy Expansion / Combination / Subcutaneously or Intravenously / Melanoma DF6002 Subcutaneous portion of the study is complete. 2L+ melanoma Dosing DF6002 Q4W Dosing nivolumab Q4W Efficacy Expansion / Combination / Subcutaneously or Intravenously / Non-Melanoma DF6002 Subcutaneous portion of the study is complete. 2L+ non-melanoma skin cancer (including cSCC, BCC, and MCC) Dosing DF6002 Q4W Dosing nivolumab Q4W
- Primary Outcome Measures
Name Time Method Number of participants with dose-limiting toxicities (DLTs) During the first 3 weeks of treatment Dose Escalation
Overall Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per an Independent Endpoint Review Committee (IERC) Up to 2 years Efficacy Expansion Arms
- Secondary Outcome Measures
Name Time Method Severity of TEAEs Up to 2 years Severity of the TEAEs seen in study participants
Clinical benefit rate (CBR) according to RECIST 1.1 per Investigator assessment Up to 2 years Overall change, if any, after treatment
Overall Survival (OS) Up to 5 years Phase 2 only
Amount of Treatment Emergent Adverse Events (TEAEs) Up to 2 years Number of participants with TEAEs
Duration of TEAEs Up to 2 years How long the TEAEs seen last
Number of participants with changes from baseline in clinical laboratory parameters Up to 2 years Overall change, if any, after treatment
Number of participants with changes from baseline in electrocardiogram (ECG) parameters Up to 2 years Overall change, if any, after treatment
Number of participants with changes from baseline in vital sign parameters Up to 2 years Overall change, if any, after treatment
Duration of Response (DOR) according to RECIST 1.1 per Investigator assessment Up to month 24 Overall change, if any, after treatment
Area under the plasma concentration-time curve from the time of dosing to the time of the last observation (AUC 0-T) Up to day 28 Overall change, if any, after treatment
Area under the plasma concentration-time curve from the time of dosing extrapolated to infinity (AUC 0-INF) Up to day 28 Overall change, if any, after treatment
Maximum serum concentration observed post-dose (Cmax) Up to day 28 Overall change, if any, after treatment
Best overall response (BOR) according to RECIST 1.1 per Investigator assessment Approximately one year Overall change, if any, after treatment
Confirmed ORR per RECIST 1.1 per Investigator assessment Up to 2 years Phase 1/1b only
Progression-free survival (PFS) according to RECIST 1.1 per Investigator assessment Up to 2 years Phase 2 only
CBR according to RECIST 1.1 per IERC Up to 2 years Phase 2 only
PFS according to RECIST 1.1 per IERC Up to 2 years Phase 2 only
DOR according to RECIST 1.1 per IERC Up to month 24 Phase 2 only
Unconfirmed response after 4 cycles according to RECIST 1.1 Up to 2 years Phase 2 only
Serum titers of anti-DF6002 antibodies Up to 2 years Phase 2 only
Serum titers of anti-nivolumab antibodies Up to 2 years Phase 2 only
Trial Locations
- Locations (32)
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Clinica Universidad de Navarra - Madrid
🇪🇸Madrid, Spain
START Madrid - Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Clinica Universidad de Navarra - Pamplona
🇪🇸Pamplona, Spain
Local Institution - 0022
🇦🇺Heidelberg, Australia
Hôpital Saint-Louis
🇫🇷Paris, France
Centre Hospitalier Lyon-Sud
🇫🇷Pierre-Benite, France
Gustave Roussy
🇫🇷Villejuif, France
Local Institution - 0023
🇦🇺Box Hill, Australia
SCRI - HealthOne Denver
🇺🇸Denver, Colorado, United States
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
University of California Irvine
🇺🇸Orange, California, United States
Institut Bergonié
🇫🇷Bordeaux Cedex, France
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Miami
🇺🇸Miami, Florida, United States
Augusta University Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Local Institution
🇺🇸Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
HealthPartners Cancer Center at Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Atlantic Health System
🇺🇸Morristown, New Jersey, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
SCRI - Tennessee Oncology - Saint Thomas West Clinic
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute and Hospital
🇺🇸Salt Lake City, Utah, United States
USOR - Virginia Cancer Specialists - Fairfax Office
🇺🇸Fairfax, Virginia, United States
Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States