Study of DF6215 in Patients With Advanced Solid Tumors

Solid Tumor, Adult Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06108479
• Other study ID #: DF6215-001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 28, 2023
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Dragonfly Therapeutics
• Contact: Sean Rossi
• Phone: 617-588-0086
• Email: sean.rossi[@]dragonflytx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: December 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• 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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Drug:
• DF6215
Immunotherapy (cytokine) targeting effector cells.

Locations

Country	Name	City	State
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
France	Institut Paoli-Calmettes	Marseille
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Sarcoma Oncology Center	Santa Monica	California
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Dragonfly Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.