Clinical Trials /

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

NCT04423029

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 pembrolizumab.

Related Conditions:
  • Breast Carcinoma
  • Cancer
  • Cervical Carcinoma
  • Classical Hodgkin Lymphoma
  • Endometrial Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Melanoma
  • Merkel Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
  • Primary Mediastinal B-Cell Lymphoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation of DF6002 in Patients With Advanced Solid Tumors, and Expansion in Selected Indications
  • 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 Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications

Clinical Trial IDs

  • ORG STUDY ID: DF6002-001
  • NCT ID: NCT04423029

Conditions

  • Solid Tumor
  • Melanoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
DF6002DF6002 In Combination with Keytruda Escalation
PembrolizumabKeytrudaDF6002 In Combination with Keytruda Escalation

Purpose

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 pembrolizumab.

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 pembrolizumab.

      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 pembrolizumab 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 pembrolizumab in the following
      indication:

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

      In each study phase, patients will receive DF6002 on Day 1 every 3 weeks (Q3W). 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.
    

Trial Arms

NameTypeDescriptionInterventions
DF6002 Monotherapy Dose EscalationExperimental3+3 dose escalation of subcutaneous DF6002 as monotherapy in patients with solid tumors.
  • DF6002
DF6002 Monotherapy Expansion (Melanoma)ExperimentalDose expansion of up to 40 patients with melanoma receiving subcutaneous DF6002 as monotherapy.
  • DF6002
DF6002 Monotherapy Expansion (Renal Cell)ExperimentalDose expansion of up to 40 patients with renal cell carcinoma receiving subcutaneous DF6002 as monotherapy.
  • DF6002
DF6002 In Combination with Keytruda EscalationExperimental3+3 dose escalation of subcutaneous DF6002 in combination with intravenous Keytruda.
  • DF6002
  • Pembrolizumab
DF6002 in Combination with Keytruda Expansion (Urothelial)ExperimentalDose expansion of up to 40 patients with urothelial carcinoma receiving subcutaneous DF6002 in combination with intravenous Keytruda.
  • DF6002
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria (General Phase 1):

          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

          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 Expansion Inclusion Criteria:

          7. Has measurable disease in one of the following tumor types: melanoma, non-small cell
             lung cancer, small cell lung cancer, head and neck squamous cell carcinoma , classical
             Hodgkin lymphoma, primary mediastinal large B-Cell lymphoma, urothelial carcinoma,
             micro-satellite instability high cancer, gastric cancer, esophageal cancer, cervical
             cancer, hepatocellular cancer, Merkel cell carcinoma, renal cell carcinoma,
             endometrial cancer, cutaneous T cell lymphoma, or triple negative breast cancer.

          8. Agrees to undergo a pre-treatment biopsy and another biopsy while on treatment

        Inclusion Criteria for Phase 1b, DF6002 in Combination with Pembrolizumab

          1. Male or female patients aged ≥ 18 years.

          2. Histologically or cytologically proven locally advanced or metastatic solid tumors.

          3. Eligible to receive pembrolizumab per its US label

          4. ECOG performance status of 0 or 1.

          5. Clinical or radiological evidence of disease.

          6. Adequate hematological, hepatic and renal function.

          7. Resolution of toxic effect(s) of the prior anti-cancer therapy to ≤Grade 1 (Patients
             with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are exceptions.)

             Additional Inclusion Criteria for Patients in the Phase 1b Expansion Cohort:

          8. Has measurable disease in one of the following tumor types: melanoma, NSCLC, SCLC,
             HNSCC, classical Hodgkin lymphoma, primary mediastinal large B-Cell lymphoma,
             urothelial carcinoma, micro-satellite instability high cancer, gastric cancer,
             oesophageal cancer, cervical cancer, hepatocellular cancer, Merkel cell carcinoma,
             renal cell carcinoma, endometrial cancer, cutaneous T cell lymphoma.

          9. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:To assess the number of adverse events experienced during treatment with monotherapy DF6002 that meet dose limiting toxicity criteria per the study protocol.

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description:Characterize the safety profile of DF6002 by assessing the number of adverse events occurring while on treatment with DF6002.
Measure:Determine serum concentrations of DF6002 at various timepoints
Time Frame:From start of treatment up through 28 days after last treatment
Safety Issue:
Description:Concentration vs time of DF6002 will be measured using blood samples taken a various time points on study
Measure: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
Safety Issue:
Description:To assess duration of response using RECIST 1.1 criteria
Measure:Assess Best Overall Response
Time Frame:Through 90 days after completion of the study, an average of 1 year
Safety Issue:
Description:To assess best overall response using RECIST 1.1 criteria
Measure:Assess Overall Survival
Time Frame:Time from enrollment in the study until death, measured up to 2 years after last treatment on study
Safety Issue:
Description:To assess overall survival following treatment
Measure:Assess Overall Response Rate
Time Frame:Time from enrollment in the study until up to 2 years after last treatment on study
Safety Issue:
Description:To assess overall response rate according to Investigator judgment

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dragonfly Therapeutics

Trial Keywords

  • Immunotherapy
  • Cytokine
  • Solid Tumor
  • Melanoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
  • IL-12
  • DF6002

Last Updated

June 5, 2020