Study of DF6215 in Patients With Advanced Solid Tumors

Sponsor

Dragonfly Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06108479

Collaborator

(none)

102

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult	Drug: DF6215	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

102 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DF6215 Dose Escalation Dose escalation cohorts of DF6215 in sequential ascending order.	Drug: DF6215 Immunotherapy (cytokine) targeting effector cells.
Experimental: DF6215 Safety/PK/PD 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 Immunotherapy (cytokine) targeting effector cells.
Experimental: DF6215 Expansion in Advanced Melanoma 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 Immunotherapy (cytokine) targeting effector cells.

Arm

Intervention/Treatment

Experimental: DF6215 Dose Escalation

Dose escalation cohorts of DF6215 in sequential ascending order.

Drug: DF6215

Immunotherapy (cytokine) targeting effector cells.

Experimental: DF6215 Safety/PK/PD

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

Immunotherapy (cytokine) targeting effector cells.

Experimental: DF6215 Expansion in Advanced Melanoma

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

Immunotherapy (cytokine) targeting effector cells.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Assess number of adverse events observed during treatment with DF6215 [Screening visit up to 30 days after End of Treatment visit.]
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.
Evaluation of DF6215 Pharmacokinetics [From start of treatment up to 28 days after the decision to stop study treatment.]
Concentration vs time of DF6215 will be measured using blood samples taken at various time points on study.
Evaluation of DF6215 Immunogenicity [From start of treatment up to 28 days after the decision to stop study treatment.]
Evaluate immunogenicity of DF6215 by measuring the number of patients developing anti-DF6215 antibodies.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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