A Study of DF6002 Alone and in Combination With Nivolumab

• ClinicalTrials.gov Identifier: NCT04423029
• Recruitment Status: Recruiting
• First Posted: June 9, 2020
• Last Update Posted: April 20, 2023
• Sponsor: Dragonfly Therapeutics
• Information provided by (Responsible Party): Dragonfly Therapeutics

Tracking Information

• First Submitted Date: June 5, 2020
• First Posted Date: June 9, 2020
• Last Update Posted Date: April 20, 2023
• Actual Study Start Date: July 13, 2020
• Estimated Primary Completion Date: July 19, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 8, 2022)

• Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: During the first 3 weeks of treatment ]
  Phase 1/1b only
• Overall Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per an Independent Endpoint Review Committee (IERC) [ Time Frame: Up to 2 years ]
  Phase 2 only

Original Primary Outcome Measures (submitted: June 5, 2020)

• Assessment of the number of dose limiting toxicities experienced on study with monotherapy DF6002 as defined per criteria in the study protocol [ Time Frame: First 3 weeks on treatment for each subject. ]
  To assess the number of adverse events experienced during treatment with monotherapy DF6002 that meet dose limiting toxicity criteria per the study protocol.
• Assessment of the number of dose limiting toxicities experienced on study with combination therapy of DF6002 and pembrolizumab as defined per criteria in the study protocol [ Time Frame: First 3 weeks on treatment for each subject in the combination therapy cohort. ]
  To assess the number of adverse events experienced during treatment with combination therapy of DF6002 and pembrolizumab that meet dose limiting toxicity criteria per the study protocol.
• Assess overall response rate [ Time Frame: Through 90 days after completion of the study, an average of 1 year. ]
  To assess the Overall Response Rate (ORR) per RECIST version 1.1 criteria of patients in the Phase 2 expansion cohorts.

Current Secondary Outcome Measures (submitted: April 8, 2022)

• Number of participants with treatment emergent adverse events (TEAEs) [ Time Frame: Up to 2 years ]
• Severity of TEAEs [ Time Frame: Up to 2 years ]
• Duration of TEAEs [ Time Frame: Up to 2 years ]
• Number of participants with changes from baseline in clinical laboratory parameters [ Time Frame: Up to 2 years ]
• Number of participants with changes from baseline in electrocardiogram (ECG) parameters [ Time Frame: Up to 2 years ]
• Number of participants with changes from baseline in vital sign parameters [ Time Frame: Up to 2 years ]
• Number of participants with changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Up to 2 years ]
• Duration of Response (DOR) according to RECIST 1.1 per Investigator assessment [ Time Frame: 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) [ Time Frame: Up to day 28 ]
• Area under the plasma concentration-time curve from the time of dosing extrapolated to infinity (AUC 0-INF) [ Time Frame: Up to day 28 ]
• Maximum serum concentration observed post-dose (Cmax) [ Time Frame: Up to day 28 ]
• Best overall response (BOR) according to RECIST 1.1 per Investigator assessment [ Time Frame: Approximately one year ]
• Clinical benefit rate (CBR) according to RECIST 1.1 per Investigator assessment [ Time Frame: Up to 2 years ]
• Confirmed ORR per RECIST 1.1 per Investigator assessment [ Time Frame: Up to 2 years ]
  Phase 1/1b only
• Progression-free survival (PFS) according to RECIST 1.1 per Investigator assessment [ Time Frame: Up to 2 years ]
  Phase 2 only
• CBR according to RECIST 1.1 per IERC [ Time Frame: Up to 2 years ]
  Phase 2 only
• PFS according to RECIST 1.1 per IERC [ Time Frame: Up to 2 years ]
  Phase 2 only
• DOR according to RECIST 1.1 per IERC [ Time Frame: Up to month 24 ]
  Phase 2 only
• Unconfirmed response after 4 cycles according to RECIST 1.1 [ Time Frame: Up to 2 years ]
  Phase 2 only
• Overall Survival (OS) [ Time Frame: Up to 5 years ]
  Phase 2 only
• Serum titers of anti-DF6002 antibodies [ Time Frame: Up to 2 years ]
  Phase 2 only
• Serum titers of anti-nivolumab antibodies [ Time Frame: Up to 2 years ]
  Phase 2 only

Original Secondary Outcome Measures (submitted: June 5, 2020)

• Assess number of treatment emergent adverse events throughout study [ Time Frame: Until 30 days after the last treatment of the last subject enrolled in the Phase 2 portion of the study. ]
  Characterize the safety profile of DF6002 by assessing the number of adverse events occurring while on treatment with DF6002.
• Determine serum concentrations of DF6002 at various timepoints [ Time Frame: From start of treatment up through 28 days after last treatment ]
  Concentration vs time of DF6002 will be measured using blood samples taken a various time points on study
• Assess Duration of Response [ Time Frame: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months ]
  To assess duration of response using RECIST 1.1 criteria
• Assess Best Overall Response [ Time Frame: Through 90 days after completion of the study, an average of 1 year ]
  To assess best overall response using RECIST 1.1 criteria
• Assess Overall Survival [ Time Frame: Time from enrollment in the study until death, measured up to 2 years after last treatment on study ]
  To assess overall survival following treatment
• Assess Overall Response Rate [ Time Frame: Time from enrollment in the study until up to 2 years after last treatment on study ]
  To assess overall response rate according to Investigator judgment

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of DF6002 Alone and in Combination With Nivolumab
• Official Title: A Phase 1/2, 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
• 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

• Drug: DF6002
  Specified dose on specified days
• Drug: Nivolumab
  Specified dose on specified days
  Other Name: Opdivo

Study Arms

• Experimental: Monotherapy Dose Escalation
  Intervention: Drug: DF6002
• Experimental: Monotherapy Dose Expansion (Melanoma)
  Intervention: Drug: DF6002
• Experimental: Monotherapy Dose Expansion (NSCLC)
  Intervention: Drug: DF6002
• Experimental: Combination Dose Escalation
  Interventions:

  • Drug: DF6002
  • Drug: Nivolumab
• Experimental: Combination Dose Expansion (Melanoma)
  Interventions:

  • Drug: DF6002
  • Drug: Nivolumab
• Experimental: Combination Dose Expansion (NSCLC)
  Interventions:

  • Drug: DF6002
  • Drug: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 8, 2022): 473
• Original Estimated Enrollment (submitted: June 5, 2020): 260
• Estimated Study Completion Date: December 16, 2025
• Estimated Primary Completion Date: July 19, 2024 (Final data collection date for primary outcome measure)

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
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sean Rossi; 617-588-0086; sean.rossi@dragonflytx.com

• Listed Location Countries: Australia, France, Spain, United States

Administrative Information

• NCT Number: NCT04423029
• Other Study ID Numbers: CA101-001; 2021-000038-33 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dragonfly Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Dragonfly Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jean-Marie Cuillerot, MD; Chief Medical Officer

• PRS Account: Dragonfly Therapeutics
• Verification Date: April 2023