Overview

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.

Eligibility

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.