2023-510511-19-00
Not yet recruiting
Phase 1/2
A Phase 1/2, First-In-Human, Multi-Part, Open Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF6002 as a Monotherapy and in Combination with Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications
Dragonfly Therapeutics Inc.8 sites in 2 countries95 target enrollmentStarted: March 25, 2024Last updated:
Overview
- Phase
- Phase 1/2
- Status
- Not yet recruiting
- Sponsor
- Dragonfly Therapeutics Inc.
- Enrollment
- 95
- Locations
- 8
- Primary Endpoint
- The primary endpoints in Phase 1/1b are: Occurrence of DLTs during the first 3 weeks of treatment.
Overview
Brief Summary
The primary objective of Phase 1 is to: Assess the safety and tolerability of DF6002 as monotherapy, and to determine the maximum tolerated dose (MTD) of Subcutaneous (SC) DF6002 in patients with advanced (unresectable, recurrent, or metastatic) solid tumors in selected indications. The primary objective of Phase 1b is to: Assess the safety and tolerability of SC DF6002 in combination with intravenous (IV) Nivolumab, and to determine the MTD of DF6002 in combination with Nivolumab in patients with advanced (unresectable, recurrent, or metastatic) solid tumors in selected indications The primary objective of Phase 2 is: To assess the Objective Response Rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per an Independent Endpoint Review Committee (IERC), for all Efficacy Expansion Cohorts testing the clinical activity of DF6002 as a monotherapy or in combination with nivolumab.
Study Design
- Study Type
- Interventional clinical trial of medicinal product
- Allocation
- Not Applicable
- Primary Purpose
- Phase 2: Efficacy Expansion using a group sequential design
- Masking
- None
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Phase 1 (DF6002 Monotherapy) and Phase 1b (Combination with Nivolumab) Signed written informed consent.
- •Phase 1/1b Safety PK/PD Expansion Cohort Agrees to undergo a pre-treatment biopsy and another biopsy while on treatment
- •Phase 2, Advanced Melanoma (Cohort 2A and 2C) Signed written informed consent.
- •Phase 2, Advanced Melanoma (Cohort 2A and 2C) Male or female patients aged ≥18 years.
- •Phase 2, Advanced Melanoma (Cohort 2A and 2C) Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified in the American Joint Committee on Cancer staging system. a. Participants with ocular or uveal melanoma are ineligible.
- •Phase 2, Advanced Melanoma (Cohort 2A and 2C) PD-L1 status must be documented if available.
- •Phase 2, Advanced Melanoma (Cohort 2A and 2C)BRAF (V600) mutation status must be known. Both BRAF-mutated and wildtype participants are permitted in this cohort. a. BRAF-mutated participants must have been treated with approved targeted therapies.
- •Phase 2 Non-Small Cell Lung Cancer (Cohort 2B and 2D) Signed written informed consent.
- •Phase 2 Non-Small Cell Lung Cancer (Cohort 2B and 2D) Male or female patients aged ≥18 years.
- •Phase 2 Non-Small Cell Lung Cancer (Cohort 2B and 2D) Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or recurrent disease.
Exclusion Criteria
- •Concurrent treatment with a non-permitted drug (see Protocol Section 9.6.2).
- •Significant acute or chronic infections (including historic positive test for human immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C tested during the Screening window).
- •Prior treatment with rhIL2 or with any drug containing an IL2 or IL12 moiety.
- •Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [with the exception of palliative bone directed radiotherapy], immune therapy, or cytokine therapy except for erythropoietin), major surgery (excluding prior diagnostic biopsy), concurrent systemic therapy with immunosuppressive agents, or use of any investigational drug within 28 days before the start of study treatment, or concurrent systemic corticosteroids within 7 days before start of study treatment. Administration of steroids for management of allergic reactions or irAEs is allowed. Continued androgen deprivation therapy for castrate-resistant prostate cancer is permitted. Note: Patients receiving bisphosphonates are eligible provided treatment was initiated at least 14 days before the first dose of DF
- •Previous malignant disease other than the target malignancy to be investigated in this study within the last 3 years, with the exception of localized or resected basal or squamous cell carcinoma of the skin, localized prostate cancer or cervical carcinoma in situ.
- •Rapidly progressive disease.
- •Any Grade 2 and higher neurological or pulmonary toxicity during a treatment with an anti-PD-1 or PD-L1 agent administered as a monotherapy.
- •Patients with adrenal insufficiency requiring hormone replacement will be excluded from the “3+3” dose escalation.
- •Active or history of central nervous system (CNS) metastases, unless all of the following criteria are met: a. CNS lesions are asymptomatic and previously treated. b. Patient does not require ongoing steroid treatment daily for replacement for adrenal insufficiency (except oral steroids at a dose less than ≤ 10 mg prednisone [or equivalent]) c. Imaging demonstrates stability of disease 28 days from last treatment for CNS metastases.
- •Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
Outcomes
Primary Outcomes
The primary endpoints in Phase 1/1b are: Occurrence of DLTs during the first 3 weeks of treatment.
The primary endpoints in Phase 1/1b are: Occurrence of DLTs during the first 3 weeks of treatment.
The primary endpoints in Phase 2 are, for each cohort: Confirmed ORR, per RECIST 1.1, as adjudicated by an IERC.
The primary endpoints in Phase 2 are, for each cohort: Confirmed ORR, per RECIST 1.1, as adjudicated by an IERC.
Secondary Outcomes
- 1. Phase 1/1b Number, severity, and duration of treatment emergent AEs (TEAEs) for all dose groups/indications according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v5.0.
- 2. Phase 1/1b Change from baseline in laboratory parameters, electrocardiograms (ECGs), vital signs, and Eastern Cooperative Oncology Group (ECOG) performance status.
- 3. Phase 1/1b DOR according to RECIST 1.1, per Investigator assessment.
- 4. Phase 1/1b PK parameters for DF6002 (including AUC0-t, AUC0-∞, , Cmax, tmax, and t½, trough concentration [Ctrough]), and nivolumab (concentration at the end of the infusion [Ceoi] and Ctrough)
- 5. Phase 1/1b BOR, according to RECIST 1.1, per Investigator assessment.
- 6. Phase 1/1b CBR according to RECIST 1.1, per Investigator assessment.
- 7. Phase 1/1bThe confirmed ORR, per RECIST 1.1, per investigator assessment.
- 8. Phase 2 Number, severity, and duration of TEAEs for all dose groups/indications according to the NCI-CTCAE v5.0.
- 9. Phase 2 Change from baseline in laboratory parameters, ECGs, vital signs, and ECOG performance status.
- 10. Phase 2 BOR according to RECIST 1.1, per Investigator assessment.
- 11. Phase 2 PFS according to RECIST 1.1, per Investigator assessment
- 12. Phase 2 CBR according to RECIST 1.1, per Investigator assessment
- 13. Phase 2 DOR according to RECIST 1.1, per Investigator assessment
- 14. Phase 2 CBR according to RECIST 1.1, per IERC.
- 15. Phase 2 PFS according to RECIST 1.1, per IERC.
- 16. Phase 2 DOR according to RECIST 1.1, per IERC.
- 17. Phase 2 Unconfirmed response after 4 cycles according to RECIST 1.1.
- 18. Phase 2 PK parameters (including AUC0-t, AUC0-∞, , Cmax, Ctrough, tmax, and t½) (all cohorts) and additionally for nivolumab (Ceoi and Ctrough) (Cohort 2C and Cohort 2D).
Investigators
Sean Rossi
Scientific
Dragonfly Therapeutics Inc.
Study Sites (8)
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