Dose Escalation of DF1001 in Patients With Advanced Solid Tumors, and Expansion in Selected Indications

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dragonfly Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Mar 2021 → 5 Dec 2025

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Dragonfly Therapeutics, Inc

External identifiers

EU CT number

2023-503291-24-00

EudraCT number

2019-004706-10

ClinicalTrials.gov

NCT04143711

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Pharmacokinetic, Efficacy, Pharmacodynamic, Safety

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 objectives 9

1. Dose Escalation Part: To characterize the pharmacokinetics (PK), of DF1001 monotherapy
2. Dose Escalation Part: To evaluate immunogenicity of DF1001, and to correlate to its exposure and clinical activity
3. Dose Escalation Part: To assess overall survival (OS)
4. Dose Escalation Part: 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
5. Exploratory Efficacy Part: To evaluate DOR, disease control rate (DCR), progression-free survival (PFS)
6. Exploratory Efficacy Part: To evaluate the OS
7. Exploratory Efficacy Part: To further assess the safety and tolerability of DF1001 monotherapy and DF1001 combination therapy with sacituzumab govitecan-hziy
8. Exploratory Efficacy Part: To further evaluate the PK of DF1001 monotherapy and evaluate the PK of DF1001 combination therapy with Sacituzumab govitecan-hziy
9. Efficacy Expansion Part: To assess DOR for confirmed responses, confirmed BOR, and PFS of DF1001 according to RECIST 1.1

Conditions and MedDRA coding

Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. ECOG performance status of 0 to 1 at study entry.
4. 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.
5. Baseline LVEF ≥ 55% measured by echocardiography (preferred) or MUGA scan.
6. 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).
7. 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.
8. 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.
9. 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 9

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 (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.
8. Pregnancy or lactation in females during the study.
9. Serious cardiac illness or clinically relevant uncontrolled cardiac risk factors

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Dose escalation part: Occurrence of DLTs during the first 21 days of treatment.
2. Dose escalation part: Number, severity, and duration of treatmentemergent adverse events (TEAEs), treatmentrelated adverse events (trAEs), and serious adverse events (SAEs) per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (cytokine release syndromes will be reported using American Society for Transplantation and Cellular Therapy [ASTCT] criteria).
3. Dose escalation part: Adverse events of special interest (AESI) and adverse events (AEs) leading to treatment discontinuation.
4. Exploratory Efficacy Part: Number, severity, and duration of drug-related TEAEs for all cohorts and those leading to treatment discontinuation, according to NCI-CTCAE v5
5. Exploratory Efficacy Part: The ORR, according to RECIST 1.1, per Investigator assessment.
6. Efficacy Expansion Part : The confirmed ORR, according to RECIST 1.1, per Investigator assessment.

Secondary endpoints 18

1. Dose Escalation Part: PK profile.
2. Dose Escalation Part: OS from initial treatment to death from any cause.
3. Dose Escalation Part: Unconfirmed and confirmed ORR, DOR, unconfirmed and confirmed BOR, and PFS according to RECIST 1.1, per Investigator Assessment.
4. Dose Escalation Part: Immunogenicity parameters.
5. Exploratory Efficacy Part: DOR for confirmed responses according to RECIST 1.1, per Investigator assessment.
6. Exploratory Efficacy Part: DCR according to RECIST 1.1, per Investigator assessment.
7. Exploratory Efficacy Part: PFS according to RECIST 1.1, per Investigator assessment
8. Exploratory Efficacy Part: OS from initial treatment to death from any cause.
9. Exploratory Efficacy Part: SAEs.
10. Exploratory Efficacy Part: Number, severity, relationship, and duration of TEAEs for all cohorts, according to the NCICTCAE v5.0.
11. Exploratory Efficacy Part: Number, severity, and duration of trAEs according to NCI-CTCAE v5.0.
12. Exploratory Efficacy Part: Physical examination.
13. Exploratory Efficacy Part: Vital sign measurements.
14. Exploratory Efficacy Part: clinical laboratory parameters
15. Exploratory Efficacy Part: ECG parameters, Echocardiogram (ECHO) or multigated acquisition (MUGA) scan findings.
16. Exploratory Efficacy Part: Anti-drug antibody.
17. Exploratory Efficacy Part: PK profile.
18. Efficacy Expansion Part: DOR, confirmed BOR, and PFS per Investigator assessment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dragonfly Therapeutics Inc.

Sponsor organisation

Dragonfly Therapeutics Inc.

Address

35 Gatehouse Drive

City

Waltham

Postcode

02451-1215

Country

United States

Scientific contact point

Organisation

Dragonfly Therapeutics Inc.

Contact name

Clinical trial information

Public contact point

Organisation

Dragonfly Therapeutics Inc.

Contact name

Clinical trial information

Third parties 6

Locations

4 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 76 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications