Study of DF6215 in Patients with Advanced Solid Tumors
- Conditions
- Solid Tumor, AdultSolid Tumor Cancer
- Interventions
- Registration Number
- NCT06108479
- Lead Sponsor
- Dragonfly Therapeutics
- 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.
- Detailed Description
This Phase I/Ib trial involves multiple parts and includes both dose-escalation and dose-expansion phases. The primary objectives are to evaluate the safety and tolerability of DF6215, an investigational biologic agent, when administered either as a monotherapy or in combination with pembrolizumab, a known immunotherapy drug, and evaluate the clinical activity of DF6215 monotherapy and in combination with pembrolizumab. Secondary objectives include assessing pharmacokinetics, pharmacodynamics, and preliminary efficacy based on tumor response using RECIST 1.1 criteria. The trial will enroll adult patients with advanced (unresectable, recurrent, or metastatic) solid tumors, and the study design allows for dose modifications based on safety monitoring and the occurrence of dose-limiting toxicities (DLTs). The trial will also incorporate a safety monitoring committee to review data at regular intervals to ensure patient safety .
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 255
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Monotherapy Dose Escalation DF6215 Patients will receive DF6215 monotherapy, with dose levels escalated to determine the MTD of DF6215 monotherapy. Combination Therapy Dose Escalation DF6215 Patients will receive DF6215 in combination with pembrolizumab to determine the MTD of DF6215 in combination with pembrolizumab. Combination Therapy Dose Escalation pembrolizumab Patients will receive DF6215 in combination with pembrolizumab to determine the MTD of DF6215 in combination with pembrolizumab. Combination Therapy Dose Escalation KEYTRUDA® Patients will receive DF6215 in combination with pembrolizumab to determine the MTD of DF6215 in combination with pembrolizumab. Monotherapy Dose Enrichment DF6215 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. Monotherapy Expansion of DF6215 in Advanced Melanoma DF6215 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. Combination Expansion of DF6215 and pembrolizumab in PROC DF6215 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. Combination Expansion of DF6215 and pembrolizumab in PROC pembrolizumab 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. Combination Expansion of DF6215 and pembrolizumab in PROC KEYTRUDA® 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. Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma DF6215 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. Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma pembrolizumab 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. Combination Expansion of DF6215 and pembrolizumab in Advanced Melanoma KEYTRUDA® 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. Monotherapy Expansion of DF6215 in Multiple Tumor Types (Basket) DF6215 Patients with multiple tumor types will receive DF6215 monotherapy at the recommended efficacy expansion dose to evaluate the clinical activity of DF6215 in monotherapy. Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types DF6215 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. Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types pembrolizumab 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. Combination Expansion of DF6215 and pembrolizumab in Multiple Tumor Types KEYTRUDA® 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. DF6215 Monotherapy Safety/PK/PD DF6215 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.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of DF6215 Monotherapy and in Combination with Pembrolizumab First 28 days for monotherapy; first 42 days for combination therapy. Determine the maximum tolerated dose of DF6215 both as monotherapy and when combined with pembrolizumab, by assessing the occurrence of dose-limiting toxicities.
Safety and Tolerability of DF6215 Monotherapy and in Combination with Pembrolizumab Continuously throughout the study, up to 2 years. 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.
Efficacy Expansion: Clinical Activity of DF6215 monotherapy and in combination of Pembrolizumab Assessed from the start of treatment until disease progression or study end, up to 2 years. 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.
- Secondary Outcome Measures
Name Time Method 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. Evaluate the clinical activity of DF6215 monotherapy and in combination with pembrolizumab, measured by ORR, DCR, and CBR as per RECIST 1.1.
Pharmacokinetics (PK) Parameters Samples collected at predetermined time points across the first and second cycles and periodically thereafter. Assess the PK of DF6215 monotherapy and in combination with pembrolizumab at multiple dose levels, measured by PK parameters such as area under the concentration-time curve (AUC0-t), maximum concentration (Cmax), minimum concentration (Cmin), time to reach maximum concentration (tmax), and half-life (t½).
Immunogenicity: Incidence of Anti-Drug Antibodies (ADAs) Samples collected at predetermined time points across the first and second cycles and periodically thereafter. To assess the immunogenicity of DF6215 monotherapy and in combination with pembrolizumab, measured by incidence of patients with anti-drug antibodies against DF6215.
Trial Locations
- Locations (21)
The Angeles Clinic and Research Institute - West Los Angeles Office
🇺🇸Los Angeles, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
University of California San Diego Moores Cancer Center
🇺🇸San Diego, California, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
NYU Langone Health
🇺🇸New York, New York, United States
Lifespan - Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Cancer Research SA (CRSA)
🇦🇺Adelaide, South Australia, Australia
Peninsula and South East Oncology Medical (PASO)
🇦🇺Frankston, Victoria, Australia
Institut Bergonié
🇫🇷Bordeaux, France
Centre Hospitalier Universitaire de Bordeaux
🇫🇷Bordeaux, France
Centre Georges François Leclerc
🇫🇷Dijon, France
CHU de Marseille - Hôpital de la Timone
🇫🇷Marseille, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
Institut Curie
🇫🇷Paris, France
Hôpital Lyon-Sud
🇫🇷Pierre-Bénite, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, France
Institut de Cancérologie de l'Ouest - Saint-Herblain - Site René Gauducheau
🇫🇷Saint-Herblain, France
Institut Universitaire du Cancer de Toulouse Oncopole
🇫🇷Toulouse, France