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Dose Escalation of DF6002 in Patients With Advanced Solid Tumors, and Expansion in Selected Indications

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04423029
Recruitment Status : Recruiting
First Posted : June 9, 2020
Last Update Posted : October 1, 2020
Sponsor:
Information provided by (Responsible Party):
Dragonfly Therapeutics

Tracking Information
First Submitted Date  ICMJE June 5, 2020
First Posted Date  ICMJE June 9, 2020
Last Update Posted Date October 1, 2020
Actual Study Start Date  ICMJE July 10, 2020
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 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 nivolumab 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 nivolumab 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.
Original Primary Outcome Measures  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation of DF6002 in Patients With Advanced Solid Tumors, and Expansion in Selected Indications
Official Title  ICMJE 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 This study is a Phase 1/2, open-label, dose-escalation study with a consecutive parallel-group efficacy expansion study, designed to determine the safety, tolerability, PK, pharmacodynamics, and preliminary anti-tumor activity of DF6002 as monotherapy and in combination with nivolumab.
Detailed Description

This study is a Phase 1/2, open-label, dose-escalation study with a consecutive parallel-group efficacy expansion study, designed to determine the safety, tolerability, PK, pharmacodynamics, and preliminary anti-tumor activity of DF6002 as monotherapy and in combination with nivolumab.

The study consists of 3 parts:

Phase 1: Dose-escalation as a monotherapy using a 3+3 design, with Phase 1 Cohort Expansion.

Phase 1b: Dose-escalation as a combination with nivolumab using a 3+3 design, with Phase 1b Cohort Expansion.

Phase 2: Efficacy Expansion using a group sequential design.

In Phase 2, DF6002 will be evaluated as a monotherapy in the following indications:

Cohort 2A: Advanced (unresectable or metastatic) melanoma.

Cohort 2B: Advanced (unresectable or metastatic) renal cell carcinoma (RCC).

In Phase 2, DF6002 will be evaluated in combination with nivolumab in the following indication:

Cohort C: Advanced (unresectable or metastatic) urothelial carcinoma.

In each study phase, patients will receive DF6002 on Day 1 every 4 weeks (Q4W). Patients will receive DF6002 until confirmed progressive disease (PD), unacceptable toxicity (ie, dose-limiting toxicity [DLT]), or any reason for withdrawal from the study or Investigational Medicinal Product (IMP) occurs.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Melanoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
  • Lung Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Esophageal Cancer
  • Gastric Cancer
  • Ovarian Cancer
  • Prostate Cancer
Intervention  ICMJE
  • Biological: DF6002
    DF6002 is a monovalent human interleukin-12 (IL12)-constant fragment (Fc) fusion protein that binds to the IL12 receptor.
  • Biological: Nivolumab
    Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
    Other Name: Opdivo
Study Arms  ICMJE
  • Experimental: DF6002 Monotherapy Dose Escalation
    3+3 dose escalation of subcutaneous DF6002 as monotherapy in patients with solid tumors.
    Intervention: Biological: DF6002
  • Experimental: DF6002 Monotherapy Expansion (Melanoma)
    Dose expansion of up to 40 patients with melanoma receiving subcutaneous DF6002 as monotherapy.
    Intervention: Biological: DF6002
  • Experimental: DF6002 Monotherapy Expansion (Renal Cell)
    Dose expansion of up to 40 patients with renal cell carcinoma receiving subcutaneous DF6002 as monotherapy.
    Intervention: Biological: DF6002
  • Experimental: DF6002 In Combination with Opdivo Escalation
    3+3 dose escalation of subcutaneous DF6002 in combination with intravenous Opdivo.
    Interventions:
    • Biological: DF6002
    • Biological: Nivolumab
  • Experimental: DF6002 in Combination with Opdivo Expansion (Urothelial)
    Dose expansion of up to 40 patients with urothelial carcinoma receiving subcutaneous DF6002 in combination with intravenous Opdivo.
    Interventions:
    • Biological: DF6002
    • Biological: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2020)
260
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria (General Phase 1 and Phase 1b):

  1. Male or female patients aged ≥ 18 years
  2. Histologically or cytologically proven locally advanced or 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.
  3. ECOG performance status of 0 or 1
  4. Clinical or radiological evidence of disease
  5. Adequate hematological, hepatic and renal function
  6. Resolution of toxic effect(s) of prior anti-cancer therapy to ≤Grade 1 (Patients with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are exceptions)

    Additional Phase 1 Monotherapy and Phase 1b Combination With Nivolumab Expansion Inclusion Criteria:

  7. Has one of the following tumor types: melanoma, non-small cell lung cancer, or triple negative breast cancer
  8. Agrees to undergo a pre-treatment biopsy and another biopsy while on treatment

Inclusion Criteria (General Phase 2)

  1. Male or female patients aged ≥ 18 years.
  2. ECOG performance status of 0 or 1
  3. Clinical or radiological evidence of measurable disease.
  4. Adequate hematological, hepatic and renal function.
  5. Resolution of toxic effect(s) of prior anti-cancer therapy to ≤Grade 1. (Patients with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are exceptions.)
  6. Agrees to undergo a pre-treatment biopsy and another biopsy while on treatment.

Additional Inclusion Criteria for Phase 2 (Advanced Melanoma Patients)

  1. Received treatment with an anti PD-1 antibody for at least 6 weeks.
  2. Disease progression was confirmed at least 4 weeks after the initial diagnosis of disease progression while receiving an anti PD-1 antibody.
  3. Received a BRAF inhibitor if the tumor carries a BRAF activating mutation and progressed after the last line of treatment.

Additional Inclusion Criteria for Phase 2 (Advanced Renal Cell Carcinoma)

  1. Any clear cell histology component
  2. Prior treatment with an anti PD-1/PD-L1 antibody or an anti-vascular endothelial growth factor therapy, as monotherapy or in combination.
  3. Received ≤3 prior lines of therapy.

Additional Inclusion Criteria for Phase 2 (Advanced Urothelial Carcinoma)

  1. Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary urothelial, urethra).
  2. Received only one platinum-containing regimen for inoperable locally advanced or metastatic urothelial carcinoma with radiographic progression or with recurrence within 6 months after the last administration of a platinum-containing regimen as an adjuvant, which would be considered failure of a first-line, platinum-containing regimen.
  3. Received no more than 2 lines of therapy (including the platinum-containing regimen) for the treatment of metastatic disease.
  4. Have not received treatment with a check point inhibitor (ie, anti-PD-1 or anti-PD-L1) as a monotherapy or in combination with a platinum-based chemotherapy

Exclusion Criteria for All Patients (All Phases)

  1. Prior treatment with rhIL2 or any recombinant long acting drug containing an IL2 moiety.
  2. Concurrent anticancer treatment (with the exception of palliative bone directed radiotherapy), immune therapy, or cytokine therapy, major surgery, concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of study treatment.
  3. 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.
  4. Rapidly progressive disease.
  5. Any Grade 2 and higher neurological or pulmonary toxicity during a treatment with an anti-PD-1 or PD-L1 agent administered as a monotherapy.
  6. Active or history of central nervous system (CNS) metastases. Melanoma patients with brain metastasis(ses) are eligible if they have been stable for 4 weeks after treatment.
  7. Receipt of any organ transplantation, autologous or allogeneic stem-cell transplantation.
  8. Significant acute or chronic infections, or active or latent hepatitis B or active hepatitis C.
  9. Preexisting autoimmune disease needing treatment with systemic immunosuppressive agents for more than 28 days within the last 3 years, or clinically relevant immunodeficiencies.
  10. Known severe hypersensitivity reactions to monoclonal antibodies and any history of anaphylaxis, or uncontrolled asthma
  11. Serious cardiac illness or medical conditions.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sean Rossi (617) 588-0086 ext 760 SeanR@Dragonflytx.com
Contact: Jeannette Hasapidis Jeannette@Dragonflytx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04423029
Other Study ID Numbers  ICMJE DF6002-001
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  ICMJE Not Provided
Responsible Party Dragonfly Therapeutics
Study Sponsor  ICMJE Dragonfly Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Tapan Maniar, MD Dragonfly Therapeutics
PRS Account Dragonfly Therapeutics
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP