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BRIEF TITLE: DF6002 as a Monotherapy and in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications

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


  • Org Study ID: DF6002-001
  • Secondary ID:
  • NCT ID: NCT04423029
  • NCT Alias:
  • Sponsor: Dragonfly Therapeutics - Industry
  • Source: Dragonfly Therapeutics

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 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.

Overal Status Start Date Phase Study Type
Recruiting July 10, 2020 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Assessment of the number of dose limiting toxicities experienced on study with monotherapy DF6002 as defined per criteria in the study protocol

Primary Outcome 1 - Time Frame: First 3 weeks on treatment for each subject.

Primary Outcome 2 - Measure: 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

Primary Outcome 2 - Time Frame: First 3 weeks on treatment for each subject in the combination therapy cohort.

Primary Outcome 3 - Measure: Assess overall response rate

Primary Outcome 3 - Time Frame: Through 90 days after completion of the study, an average of 1 year.

Condition:

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

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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Tapan Maniar, MD

Role: Study Director

Affiliation: Dragonfly Therapeutics

Overall Contact

Name: Sean Rossi

Phone: (617) 588-0086

Email: SeanR@Dragonflytx.com

Location

Facility Status Contact
Rhode Island Hospital
Providence, Rhode Island 02903
United States
Recruiting Andrew Schumacher
401-444-3234
ASchumacher@Lifespan.org