Study of DF6215 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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DF6215-001 is a study of a modified human cytokine (interleukin-2; IL-2) that retains the ability to bind to a certain part of the IL-2 receptor on a subset of white blood cells (lymphocytes), which can help recognize and kill tumor cells. The study will occur in two phases. The first phase will be a dose escalation phase, enrolling patients with various types of solid tumors. The second phase, Phase 1b, will include a dose expansion using the best dose selected from the first phase of the study. A cohort will be opened with eligible patients having a select solid tumor.

Official Title
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A Phase 1/1b, First-In-Human, Multi-Part, Open-Label Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of DF6215 in Patients With Advanced (Unresectable, Recurrent, or Metastatic) Solid Tumors

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: DF6215


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria - General (applies to all cohorts) Signed written informed consent Male or female patients aged ≥ 18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry and an estimated life expectancy of at least 3 months Adequate hematological function Adequate cardiac function Effective contraception Inclusion Criteria - 3+3 Dose Escalation Histologically or cytologically proven locally advanced or metastatic solid tumor, for which no standard therapy exists, or standard therapy has failed Evidence of objective disease (but participation does not require a measurable lesion) Archived tumor biopsy. If archival tissue is unavailable, a fresh tumor biopsy is required, obtained within the screening window. Inclusion Criteria - Safety/PK/PD Histologically or cytologically proven locally advanced or metastatic solid tumor from the following list, where standard therapy does not exist or has failed: Melanoma HPV-positive advanced malignancies Ovarian cancer Head and neck cancer Lung cancer (non-small-cell lung cancer [NSCLC]) Renal cell carcinoma (RCC) Other tumor types may be eligible after discussion with the Sponsor medical monitor Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1 A fresh tumor biopsy must be obtained during the screening window and on-treatment Inclusion Criteria - Efficacy Expansion Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1 A fresh tumor biopsy must be obtained during the screening window and on-treatment Key Exclusion Criteria - General (applies to all cohorts) Patients receiving chemotherapy, radiotherapy (other than palliative bone-directed radiotherapy), major surgery, or receiving another therapeutic agent within 28 days before the start of study drug or within 5 half-lives of the previous therapeutic agent (if known), whichever is shorter Patients receiving immune checkpoint inhibitor therapy within 3 months before the start of study drug Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [except for 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 treatment or within 5 half-lives of the previous therapeutic agent (if known), whichever is shorter. Short-term administration of systemic steroids (eg, for allergic reactions or the management of immune-related adverse events [irAEs]) is allowed. Note: Patients receiving bisphosphonate or denosumab are eligible, provided treatment was initiated at least 14 days before the first dose of DF6215 Previous malignant disease (other than the target malignancy to be investigated in this study) within the last 3 years, with the exception of basal or squamous cell carcinoma of the skin, low-grade prostate cancer (Gleason score ≤ 6 and must be Stage I or II), or cervical carcinoma in situ Life expectancy of less than 3 months Patients with brain metastases are excluded, unless all of the following criteria are met: Central nervous system (CNS) lesions are asymptomatic and previously treated Patient does not require ongoing daily steroid treatment for replacement for adrenal insufficiency (except ≤ 10 mg prednisone [or equivalent]) Imaging demonstrates stable disease 28 days after last treatment Receipt of any organ transplant, including autologous or allogeneic stem-cell transplantation Pregnancy or lactation during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DF6215 Dose Escalation<br>Dose escalation cohorts of DF6215 in sequential ascending order. | Drug: DF6215<br>* Immunotherapy (cytokine) targeting effector cells.<br>|
| Experimental: DF6215 Safety/PK/PD<br>Expansion cohorts of DF6215 in multiple dose levels after evaluation for safety in the DF6215 Dose Escalation arm. Additional Pharmacokinetic (PK) and Pharmacodynamic (PD) samples included in this arm. | Drug: DF6215<br>* Immunotherapy (cytokine) targeting effector cells.<br>|
| Experimental: DF6215 Expansion in Advanced Melanoma<br>Expansion cohort enrolling 20 patients with advanced melanoma who have progressed after an anti-PD-1 containing regimen using the dose selected for Phase 1b identified in the DF6215 Dose Escalation arm. | Drug: DF6215<br>* Immunotherapy (cytokine) targeting effector cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of number of DLTs experienced on study as defined per criteria in the study protocol | To assess the number of adverse events experienced during the study that meet Dose Limiting Toxicity (DLT) criteria per the study protocol. | First 4 weeks of treatment for each subject. | 
| Assess ORR per RECIST 1.1 criteria | To assess the Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. | Through 90 days after completion of the study, an average of 1 year. | 
| Assess DOR per RECIST 1.1 criteria | To assess Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months. | 
| Assess PFS per RECIST 1.1 criteria | To assess Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess number of adverse events observed during treatment with DF6215 | To assess the safety of DF6215 by measuring number of subjects with Treatment-Emergent Adverse Events (TEAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. | Screening visit up to 30 days after End of Treatment visit. | 
| Evaluation of DF6215 Pharmacokinetics | Concentration vs time of DF6215 will be measured using blood samples taken at various time points on study. | From start of treatment up to 28 days after the decision to stop study treatment. | 
| Evaluation of DF6215 Immunogenicity | Evaluate immunogenicity of DF6215 by measuring the number of patients developing anti-DF6215 antibodies. | From start of treatment up to 28 days after the decision to stop study treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DF6215, DF6215-001, Immunotherapy, Melanoma, HPV-Positive Advanced Malignancies, Ovarian Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Advanced or Metastatic Solid Tumors, Antineoplastic Agents, Antineoplastic Agents, Immunological, Molecular Mechanisms of Pharmacological Action, Neoplasms