Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLGT Classification code 10027476 Term: Metastases System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: DF1001
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DF1001
Other descriptive name: DF1001
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
C
Sponsors
Dragonfly Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Common Inclusion Criteria For All Groups/Cohorts/Combinations: - 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 used, 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 318 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: Exclusion Criteria for All Patients of Both Study Parts: 1. Previous treatment with drugs that specifically target the HER2 pathway (mAb or Tyrosine Kinase Inhibitor [TKI]) is acceptable providing washout period 2. Concurrent anticancer treatment, immune therapy, or cytokine therapy 3. Life expectancy of less than 3 months. 4. Active or history of central nervous system (CNS) metastases. 5. Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation. 6. Significant acute or chronic infections 7. Preexisting autoimmune disease 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. 8. Pregnancy or lactation in females during the study. 9. Serious cardiac illness or clinically relevant uncontrolled cardiac risk factors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation Part: • To assess the safety and tolerability of DF1001 monotherapy, and to determine the Maximum Tolerated Dose (MTD) of DF1001 in patients with advanced (unresectable, recurrent, or metastatic) solid tumors. • To assess the safety and tolerability of DF1001 monotherapy, DF1001 with nivolumab and DF1001 with nab-paclitaxel combination therapies Exploratory Efficacy Part • To assess key safety and tolerability of DF1001 monotherapy and DF1001 combination therapy with sacituzumab govitecan-hziy. • To evaluate the confirmed objective response rate (ORR) of DF1001 monotherapy and DF1001 combination therapy with sacituzumab govitecanhziy. Efficacy Expansion Cohorts Part: • To assess the confirmed ORR according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per Investigator assessment. ;Secondary Objective: Dose Escalation Part: • To characterize the pharmacokinetics (PK), of DF1001 monotherapy • To evaluate immunogenicity of DF1001, and to correlate to its exposure and clinical activity • To assess overall survival (OS) • To assess unconfirmed and confirmed ORR, duration of response (DOR) for confirmed responses, unconfirmed and confirmed best overall response (BOR), and progression-free survival (PFS) according to RECIST 1.1 Exploratory Efficacy Part: • To evaluate DOR, disease control rate (DCR), progression-free survival (PFS) • To evaluate the OS • To further assess the safety and tolerability of DF1001 monotherapy and DF1001 combination therapy with sacituzumab govitecan-hziy • To further evaluate the PK of DF1001 monotherapy and evaluate the PK of DF1001 combination therapy with sacituzumab govitecan-hziy Efficacy Expansion Part: • To assess DOR for confirmed responses, confirmed BOR, and PFS of DF1001 according to RECIST 1.1 ;Primary end point(s): Dose escalation part: • Occurrence of DLTs during the first 21 days of treatment. • Number, severity, and duration of treatmentemergent adverse events ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Escalation Part : • PK profile. • OS from initial treatment to death from any cause. • Unconfirmed and confirmed ORR, DOR, unconfirmed and confirmed BOR, and PFS according to RECIST 1.1, per Investigator Assessment. • Immunogenicity parameters. Exploratory Efficacy Part : • DOR for confirmed responses according to RECIST 1.1, per Investigator assessment. • DCR according to RECIST 1.1, per Investigator assessment. • PFS according to RECIST 1.1, per Investigator assessment • OS from initial treatment to death from any cause. • SAEs. • Number, severity, relationship, and duration of TEAEs for all cohorts, according to the NCICTCAE v5.0. • Number, severity, and duration of trAEs according to NCI-CTCAE v5.0. • Physical examination. • Vital sign measurements. • clinical laboratory parameters. • ECG parameters, Echocardiogram (ECHO) or multigated acquisition (MUGA) scan findings. • Anti-drug antibody. • PK profile. Efficacy Expansion Part • DOR, confirmed BOR, and PFS per Investigator assessment. ;Timepoint(s) of evaluation of this end point: •Serum concentrations of DF1001 determined at various time points from start up through 28 days after last treatment •Evaluation of DF1001 immunogenicity every 3 weeks up to 28 days after last treatment •Assess BOR through 90 days after completion of the study an average of 1 year •Assess DOR from time of initiation of therapy until the date of first documented tumor progression assessed up to 2 years •Assess PFS from time of initiation of therapy until the date of first documented tumor progression assessed up to 2 years •Assess OS time from enrollment in the study until death measured up to 2 years after last treatment on study | — |
Countries
Belgium, Denmark, France, Netherlands, United States
Contacts
Public ContactSean Rossi
Dragonfly Therapeutics, Inc.
Outcome results
None listed