Study of DF6215 in Patients With Advanced Solid Tumors

NCT06108479 | Completed Phase 1 FDA Drug

• 3 other identifiers: DF6215-001KEYNOTE-G13MK-3475-G13
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 21

Brief Summary

A Phase I/Ib, First-In-Human, Multi-Part, Open-Label Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of DF6215 Monotherapy and in Combination Therapy in Patients with Advanced (Unresectable, Recurrent, or Metastatic) Solid Tumors; is designed to assess the safety, tolerability, and preliminary efficacy of DF6215 alone or in combination with pembrolizumab in patients with advanced solid tumors. The study is open-label, meaning both participants and investigators are aware of the treatment being administered.

Conditions

Solid Tumor, Adult; Solid Tumor Cancer

Keywords

DF6215-001; DF6215; 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; Solid Tumor; Dose Escalation; oncology; pembrolizumab; KEYTRUDA®

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) of DF6215 Monotherapy and in Combination with Pembrolizumab

  Determine the maximum tolerated dose of DF6215 both as monotherapy and when combined with pembrolizumab, by assessing the occurrence of dose-limiting toxicities.

  First 28 days for monotherapy; first 42 days for combination therapy.

• Safety and Tolerability of DF6215 Monotherapy and in Combination with Pembrolizumab

  Evaluate the safety and tolerability of DF6215 monotherapy and in combination with pembrolizumab at various dose levels by monitoring the incidence, severity, and causality of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to discontinuation, per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

  Continuously throughout the study, up to 2 years.

• Efficacy Expansion: Clinical Activity of DF6215 monotherapy and in combination of Pembrolizumab

  To evaluate the clinical activity of DF6215 monotherapy and in combination with pembrolizumab, measured by ORR per investigator assessment as defined by RECIST 1.1 in the efficacy expansion part.

  Assessed from the start of treatment until disease progression or study end, up to 2 years.

Secondary Outcomes (3)

• Clinical Activity: Objective Response Rate (ORR), Disease Control Rate (DCR), and Clinical Benefit Rate (CBR)

  Assessed every 8 weeks until disease progression or study termination, up to 2 years.

• Pharmacokinetics (PK) Parameters

  Samples collected at predetermined time points across the first and second cycles and periodically thereafter.

• Immunogenicity: Incidence of Anti-Drug Antibodies (ADAs)

  Samples collected at predetermined time points across the first and second cycles and periodically thereafter.

Study Arms (9)

Monotherapy Dose Escalation

EXPERIMENTAL

Patients will receive DF6215 monotherapy, with dose levels escalated to determine the MTD of DF6215 monotherapy.

Drug: DF6215

Combination Therapy Dose Escalation

EXPERIMENTAL

Patients will receive DF6215 in combination with pembrolizumab to determine the MTD of DF6215 in combination with pembrolizumab.

Drug: DF6215; Drug: pembrolizumab; Drug: KEYTRUDA®

Monotherapy Dose Enrichment

EXPERIMENTAL

Patients with advanced melanoma after prior anti-PD-1 treatment will receive DF6215 monotherapy at two different dose levels to further characterize the doses selected during the Dose Escalation (monotherapy) part.

Drug: DF6215

Monotherapy Expansion of DF6215 in Advanced Melanoma

EXPERIMENTAL

Patients with advanced melanoma after prior anti-PD-1 will receive DF6215 monotherapy at the recommended efficacy expansion dose to evaluate the clinical activity of DF6215 in monotherapy.

Drug: DF6215

Combination Expansion of DF6215 and pembrolizumab in PROC

EXPERIMENTAL

Patients with platinum-resistant ovarian cancer (PROC) will receive DF6215 in combination with pembrolizumab at the recommended efficacy expansion dose to evaluate the clinical activity of DF6215 in combination with pembrolizumab.

Drug: DF6215; Drug: pembrolizumab; Drug: KEYTRUDA®

Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma

EXPERIMENTAL

Patients with advanced melanoma after prior anti-PD-1 therapy will receive DF6215 in combination with pembrolizumab at the recommended combination efficacy expansion dose to evaluate the clinical activity of DF6215 in combination with pembrolizumab.

Drug: DF6215; Drug: pembrolizumab; Drug: KEYTRUDA®

Monotherapy Expansion of DF6215 in Multiple Tumor Types (Basket)

EXPERIMENTAL

Patients with multiple tumor types will receive DF6215 monotherapy at the recommended efficacy expansion dose to evaluate the clinical activity of DF6215 in monotherapy.

Drug: DF6215

Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types

EXPERIMENTAL

Patients with multiple tumor types will receive DF6215 in combination with pembrolizumab at the recommended combination efficacy expansion dose to evaluate the clinical activity of DF6215 in combination with pembrolizumab.

Drug: DF6215; Drug: pembrolizumab; Drug: KEYTRUDA®

DF6215 Monotherapy Safety/PK/PD

EXPERIMENTAL

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

Interventions

DF6215 DRUG

Immunotherapy (cytokine) targeting effector cells.

Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma; Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types; Combination Expansion of DF6215 and pembrolizumab in PROC; Combination Therapy Dose Escalation; DF6215 Monotherapy Safety/PK/PD; Monotherapy Dose Enrichment; Monotherapy Dose Escalation; Monotherapy Expansion of DF6215 in Advanced Melanoma; Monotherapy Expansion of DF6215 in Multiple Tumor Types (Basket)

pembrolizumab DRUG

Anti-PD-1 immunotherapy agent

Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma; Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types; Combination Expansion of DF6215 and pembrolizumab in PROC; Combination Therapy Dose Escalation

KEYTRUDA® DRUG

Anti-PD-1 immunotherapy agent

Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma; Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types; Combination Expansion of DF6215 and pembrolizumab in PROC; Combination Therapy Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• An estimated life expectancy of ≥ 3 months.
• Adequate hematological function.
• Normal pulmonary function.
• Adequate hepatic function.
• Adequate renal function.
• Effective Contraception.

You may not qualify if:

• Patients receiving chemotherapy, radiotherapy (other than palliative bone-directed radiotherapy), major surgery, or receiving another systemic anticancer therapeutic agent within 28 days before the start of study drug(s) or within 5 half-lives of the previous therapeutic agent (if known), whichever is shorter.
• Patients receiving any of the following concurrent anticancer treatments or investigational drugs within 28 days before the start of the study drug(s), or within 5 half-lives of the previous therapeutic agent (if known), whichever is shorter:
• Cytoreductive therapy
• Radiotherapy (except for palliative bone-directed radiotherapy)
• Note: ≤ 2 weeks of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study drug.
• Immune therapy
• Cytokine therapy (except for erythropoietin)
• Major surgery (excluding prior diagnostic biopsy)
• Concurrent systemic therapy with steroids or other immunosuppressive agents.
• Note that short-term administration of systemic steroids (eg, for allergic reactions or the management of irAEs) and physiologic dose steroids (≤ 10 mg prednisone, or equivalent) for those with treated brain metastases are allowed. Patients receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug(s) will be excluded.
• Bisphosphonate or denosumab initiated within 14 days of the first dose of study drug(s)
• Previous malignant disease, other than the target malignancies to be investigated in this study, within the last 3 years. Exceptions (eg, 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) may be considered on a case-by-case basis, in consultation with the Medical Monitor.
• Any of the following cardiac abnormalities:
• A clinically relevant abnormality on the electrocardiogram (ECG)
• Clinically relevant coronary artery disease (CAD) or uncontrolled congestive heart failure

Sponsors & Collaborators

• Dragonfly Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (21)

The Angeles Clinic and Research Institute - West Los Angeles Office

Los Angeles, California, 90025, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

University of California San Diego Moores Cancer Center

San Diego, California, 92093, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Lifespan - Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Cancer Research SA (CRSA)

Adelaide, South Australia, 5000, Australia

Location

Peninsula and South East Oncology Medical (PASO)

Frankston, Victoria, 3199, Australia

Location

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, 33075, France

Location

Centre Georges François Leclerc

Dijon, 21000, France

Location

CHU de Marseille - Hôpital de la Timone

Marseille, 13005, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

Institut Curie

Paris, 75005, France

Location

Hôpital Lyon-Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86000, France

Location

Institut de Cancérologie de l'Ouest - Saint-Herblain - Site René Gauducheau

Saint-Herblain, 44805, France

Location

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, 31100, France

Location

MeSH Terms

Conditions

Melanoma; Ovarian Neoplasms; Head and Neck Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: October 31, 2023
• Study Start: November 28, 2023
• Primary Completion: December 4, 2025
• Study Completion: December 4, 2025
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10); US (9); AU (2)