Clinical trial NCT04423029: A Study of DF6002 Alone and in Combination With Nivolumab
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Advanced or Metastatic Solid Tumors
Melanoma
Non-small Cell Lung Cancer
Nivolumab
DF6002
Lead sponsor: Dragonfly Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-06-09
Enrollment: 438
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: During the first 3 weeks of treatment
measure: Overall Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per an Independent Endpoint Review Committee (IERC)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Amount of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 2 years
measure: Severity of TEAEs
timeFrame: Up to 2 years
measure: Duration of TEAEs
timeFrame: Up to 2 years
measure: Number of participants with changes from baseline in clinical laboratory parameters
timeFrame: Up to 2 years
measure: Number of participants with changes from baseline in electrocardiogram (ECG) parameters
timeFrame: Up to 2 years
measure: Number of participants with changes from baseline in vital sign parameters
timeFrame: Up to 2 years
measure: Duration of Response (DOR) according to RECIST 1.1 per Investigator assessment
timeFrame: Up to month 24
measure: Area under the plasma concentration-time curve from the time of dosing to the time of the last observation (AUC 0-T)
timeFrame: Up to day 28
measure: Area under the plasma concentration-time curve from the time of dosing extrapolated to infinity (AUC 0-INF)
timeFrame: Up to day 28
measure: Maximum serum concentration observed post-dose (Cmax)
timeFrame: Up to day 28
measure: Best overall response (BOR) according to RECIST 1.1 per Investigator assessment
timeFrame: Approximately one year
measure: Clinical benefit rate (CBR) according to RECIST 1.1 per Investigator assessment
timeFrame: Up to 2 years
measure: Confirmed ORR per RECIST 1.1 per Investigator assessment
timeFrame: Up to 2 years
measure: Progression-free survival (PFS) according to RECIST 1.1 per Investigator assessment
timeFrame: Up to 2 years
measure: CBR according to RECIST 1.1 per IERC
timeFrame: Up to 2 years
measure: PFS according to RECIST 1.1 per IERC
timeFrame: Up to 2 years
measure: DOR according to RECIST 1.1 per IERC
timeFrame: Up to month 24
measure: Unconfirmed response after 4 cycles according to RECIST 1.1
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Serum titers of anti-DF6002 antibodies
timeFrame: Up to 2 years
measure: Serum titers of anti-nivolumab antibodies
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Denver
country: United States
facility: SCRI - HealthOne Denver
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia Cancer Center
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Boston
country: United States
facility: Local Institution
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Paul
country: United States
facility: HealthPartners Cancer Center at Regions Hospital
state: Minnesota
city: Morristown
country: United States
facility: Atlantic Health System
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology - Saint Thomas West Clinic
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute and Hospital
state: Utah
city: Fairfax
country: United States
facility: USOR - Virginia Cancer Specialists - Fairfax Office
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: Box Hill
country: Australia
facility: Local Institution - 0023
city: Heidelberg
country: Australia
facility: Local Institution - 0022
city: Bordeaux Cedex
country: France
facility: Institut Bergonié
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Pierre-Benite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Villejuif
country: France
facility: Gustave Roussy
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: START Madrid - Hospital Universitario Fundación Jiménez Díaz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
Study officials:
affiliation: Dragonfly Therapeutics
name: Clinical Trials
role: STUDY_CHAIR
References: