Phase I/II Study of DF1001, Nivolumab, and Paclitaxel Albumin-Bound in Locally Advanced or Metastatic Solid Tumors
- Trial ID
- 2023-503291-24-00
- Protocol
- DF1001-001
- Sponsor
- Dragonfly Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **safety** and **tolerability** of DF1001 monotherapy and combination therapies in patients with advanced solid tumors. This includes determining the Maximum Tolerated Dose (MTD) of DF1001. Evaluating safety and tolerability is crucial for identifying potential adverse effects and ensuring patient safety during treatment. Additionally, the study aims to assess the confirmed Objective Response Rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), which is essential for understanding the therapeutic efficacy of DF1001 in this patient population.
Secondary objectives include: - Characterizing the **pharmacokinetics** (PK) of DF1001 monotherapy. - Evaluating the **immunogenicity** of DF1001 and correlating it with exposure and clinical activity. - Assessing overall survival (OS). - Evaluating unconfirmed and confirmed ORR, duration of response (DOR) for confirmed responses, best overall response (BOR), and progression-free survival (PFS) according to RECIST 1.1. - Evaluating DOR, disease control rate (DCR), and PFS. - Further assessing the safety and tolerability of DF1001 monotherapy and combination therapy with sacituzumab govitecan-hziy. - Further evaluating the PK of DF1001 monotherapy and combination therapy with sacituzumab govitecan-hziy. - Assessing DOR for confirmed responses, confirmed BOR, and PFS of DF1001 according to RECIST 1.1.
Participants
The clinical trial involves a total of **214 participants** diagnosed with **locally advanced or metastatic solid tumors**. The study population includes both male and female subjects aged 18 years and older, with an **ECOG performance status** of 0 to 1 at study entry, indicating a generally good health status. Participants were selected based on specific inclusion criteria, including measurable disease and adequate organ function. The trial population is diverse, encompassing individuals from various backgrounds, and includes vulnerable populations. Lifestyle considerations such as diet, physical activity, and habits are not specified in the available data. The selection process ensures that participants have adequate hematological, hepatic, and renal function, and are willing to use appropriate contraception methods as defined in the protocol. The trial aims to assess the safety and tolerability of DF1001 monotherapy and combination therapies in this patient group.
Plans and Procedures
The clinical trial is designed as a **Phase I/II**, first-in-human, multi-part, open-label, multiple-ascending dose study. The primary objective is to investigate the safety, tolerability, pharmacokinetics, biological, and clinical activity of DF1001 in patients with locally advanced or metastatic solid tumors. The trial will also explore the efficacy of DF1001 in combination with other agents such as **nivolumab** and **sacituzumab govitecan**. The study is expected to run from October 22, 2019, to October 22, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, performance status, and organ function. Following successful screening, participants will enter the dose escalation phase, where the maximum tolerated dose of DF1001 will be determined. Subsequent visits will involve regular monitoring for adverse events, assessment of drug efficacy, and collection of pharmacokinetic data. The trial includes exploratory efficacy and efficacy expansion cohorts to further evaluate the objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
The expected length of participant involvement varies depending on the cohort and response to treatment, with regular follow-up visits scheduled to monitor safety and efficacy. Conditions that may lead to early termination from the study include the occurrence of dose-limiting toxicities, severe adverse events, or withdrawal of consent. The trial's primary endpoints focus on the occurrence of dose-limiting toxicities and the number, severity, and duration of treatment-emergent adverse events. Secondary endpoints include pharmacokinetic profiling, overall survival, and progression-free survival.
Treatment
The clinical trial involves the administration of several experimental medications, each with distinct pharmaceutical forms and active substances. **Abraxane**, a **powder for dispersion for infusion**, contains the active substance **paclitaxel albumin-bound**. It is administered via **intravenous use**. The concentration of the formulation is 5 mg/mL. This medication is produced by Bristol-Myers Squibb Pharma EEIG and is classified under the ATC code L01CD01, indicating its role as an antineoplastic agent. The administration schedule and dosage are determined based on the study protocol, with compliance monitored through standard clinical trial procedures.
**DF1001** is another investigational product used in this study. It is a **solution for infusion** containing the active substance **DF1001**, a protein-based therapeutic. This product is also administered intravenously. Dragonfly Therapeutics, Inc. is responsible for its production. The dosing regimen for DF1001 is designed to assess its safety, tolerability, and pharmacokinetics in patients with advanced solid tumors. Participant compliance is ensured through regular monitoring and documentation of infusion sessions.
The trial also includes the use of **sacituzumab govitecan**, which is administered as a **PHF00230MIG** formulation. This investigational product is used as a comparator in the study and is delivered via intravenous infusion. The specific dosing schedule and administration details are outlined in the study protocol, with adherence monitored by the clinical trial team.
Additionally, **Opdivo**, a **concentrate for solution for infusion**, is utilized in the trial. The active substance in Opdivo is **nivolumab**, a protein-based therapeutic agent. It is administered intravenously at a concentration of 10 mg/mL. Bristol-Myers Squibb Pharma EEIG manufactures this product, which is used in combination with other investigational drugs to evaluate its efficacy and safety in the treatment of solid tumors. The administration and dosing of Opdivo are conducted according to the trial's guidelines, with participant compliance closely monitored.
Efficacy
Efficacy in this clinical trial will be assessed through several key parameters. The primary endpoint for the exploratory efficacy part is the confirmed **Objective Response Rate (ORR)**, evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per Investigator assessment. This will be measured for both DF1001 monotherapy and DF1001 combination therapy with sacituzumab govitecan-hziy. The efficacy expansion cohorts will also focus on assessing the confirmed ORR using the same criteria.
Secondary endpoints include the Duration of Response (DOR) for confirmed responses, Disease Control Rate (DCR), and Progression-Free Survival (PFS), all evaluated according to RECIST 1.1 per Investigator assessment. Overall Survival (OS) from initial treatment to death from any cause will also be monitored. Additional secondary endpoints involve the pharmacokinetic (PK) profile, immunogenicity parameters, and the number, severity, and duration of treatment-emergent adverse events (TEAEs) and treatment-related adverse events (trAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
These efficacy parameters will be collected and analyzed at various timepoints throughout the trial, with specific attention to the safety and tolerability of the treatments. The assessments will be conducted using validated scales and criteria, ensuring a comprehensive evaluation of the therapeutic impact of DF1001 and its combinations in patients with locally advanced or metastatic solid tumors.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed written informed consent.
- Male or female patients aged ≥ 18 years.
- ECOG performance status of 0 to 1 at study entry.
- Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1. (Not applicable to "Accelerated Titration and 3+3 Dose Escalation" cohorts.
- Baseline LVEF ≥ 55% measured by echocardiography (preferred) or MUGA scan.
- Adequate hematological function defined by white blood cell (WBC) count ≥ 3 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 75 × 109/L (in Dose Escalation, Safety/PK/PD, and Dose Expansion parts), platelet count ≥ 100 × 109/L (in Efficacy Expansion part), and hemoglobin ≥ 9 g/dL (may have been transfused but must show hematologic count stability for 14 days from the time of transfusion to C1D1).
- Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN). Aspartate aminotransferase (AST) level ≤ 2.5 × ULN, and an alanine aminotransferase (ALT) level ≤ 2.5 × ULN or, for patients with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN. Patients with known Gilbert Disease who have serum bilirubin level ≤ 3 ULN may be enrolled.
- Adequate renal function defined by an estimated creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault formula or another calculation of measurement method as according to local standards.
- Subjects must be willing to use appropriate contraception as defined in the protocol. Effective contraception for women of childbearing potential (WOCBP) and male patients as defined by World Health Organization (WHO) guidelines for 1 "highly effective" method or 2 "effective" methods. CTFG. WOCBP require use of a highly effective contraceptive measure. Contraception methods with low user dependency should preferably be 1used, in particular when contraception is introduced as a result of participation in the clinical trial for 120 days after last dose. A male subject should use condom during treatment and until the end of relevant systemic exposure in the male subject plus a further 90-day period. For a non-pregnant WOCBP partner, contraception recommendations should also be considered
Exclusion Criteria
- Previous treatment with drugs that specifically target the HER2 pathway (mAb or Tyrosine Kinase Inhibitor [TKI]) is acceptable providing washout period
- Concurrent anticancer treatment, immune therapy, or cytokine therapy
- Life expectancy of less than 3 months.
- Active or history of central nervous system (CNS) metastases.
- Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
- Significant acute or chronic infections
- Preexisting autoimmune disease (except for patients with vitiligo) needing treatment with systemic immunosuppressive agents ≥ 28 days within the last 3 years or clinically relevant immunodeficiencies (e.g, dys-gammaglobulinemia or congenital immunodeficiencies), or fever Grade 2 or higher within 7 days of Day 1. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.
- Pregnancy or lactation in females during the study.
- Serious cardiac illness or clinically relevant uncontrolled cardiac risk factors
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 22 Oct 2019 | 39 |
 Denmark | Not Recruiting | 22 Oct 2019 | 8 |
 France | Not Recruiting | 22 Oct 2019 | 113 |
 The Netherlands | Not Recruiting | 22 Oct 2019 | — |
| Netherlands | — | — | 14 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
OPDIVO 10 mg/mL concentrate for solution for infusion. | Comparator | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | — | — | PRD2941375 |
DF1001 | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | — | — | PRD8217878 |
Abraxane 5 mg/ml powder for dispersion for infusion. | Test | POWDER FOR DISPERSION FOR INFUSION | INTRAVENOUS USE | — | — | PRD9254303 |
SACITUZUMAB GOVITECAN | Test | PHF00230MIG | INTRAVENOUS USE | — | — | SCP53436014 |