Dose Escalation of DF6002 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

8 Nov 2021 → 26 Nov 2025

Decision date (initial)

2024-04-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Dragonfly Therapeutics, Inc.

External identifiers

EU CT number

2023-510511-19-00

EudraCT number

2021-000038-33

ClinicalTrials.gov

NCT04423029

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacogenetic, Dose response, Pharmacodynamic, Pharmacogenomic

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.

Secondary objectives 13

1. Phase 1: Characterize the safety of DF6002 as a monotherapy and in combination with nivolumab.
2. Phase 1: Characterize the pharmacokinetics (PK) of DF6002 and the PK profiles of DF6002 and nivolumab when given in combination.
3. Phase 1: Evaluate immunogenicity of DF6002.
4. Phase 1: Evaluate the immunogenicity of nivolumab, when given in combination with DF6002.
5. Phase 1: Assess ORR, as determined by the Investigator using RECIST 1.1.
6. Phase 1: Assess duration of response (DOR), as determined by the Investigator using RECIST 1.1.
7. Phase 1: Assess clinical benefit rate (CBR), as determined by the Investigator.
8. Phase 2: Characterize the safety of DF6002 as a monotherapy and in combination with nivolumab.
9. Phase 2: Characterize the PK of DF6002 as a monotherapy and the PK profiles of DF6002 and nivolumab when given in combination.
10. Phase 2: Assess DOR per an IERC using RECIST 1.1.
11. Phase 2: Assess CBR per IERC using RECIST 1.1. CBR is defined as the percentage of patients with complete response (CR), partial response (PR), or stable disease (SD) as best response.
12. Phase 2: Evaluate the immunogenicity of DF6002 as a monotherapy and each of DF6002 and nivolumab when give in combination, and investigate potential correlation between exposure and clinical activity.
13. Phase 2: Assess progression free survival (PFS) per an IERC using RECIST 1.1. Assess median overall survival (OS) time.

Conditions and MedDRA coding

Advanced Solid Tumors

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. 1. Phase 1 (DF6002 Monotherapy) and Phase 1b (Combination with Nivolumab) Signed written informed consent.
2. 2. Phase 1 (DF6002 Monotherapy) and Phase 1b (Combination with Nivolumab) Male or female patients aged ≥ 18 years.
3. 3. Phase 1 (DF6002 Monotherapy) and Phase 1b (Combination with Nivolumab) Histologically or cytologically proven locally advanced or metastatic solid tumors, for which no standard therapy exists or standard therapy has failed among the following tumor types: melanoma, NSCLC, small cell lung, head and neck squamous cell, urothelial, gastric, esophageal, cervical, hepatocellular, Merkel cell, cutaneous squamous cell carcinoma, renal cell, endometrial, TNBC, ovarian, and prostate.
4. 4. Phase 1 (DF6002 Monotherapy) and Phase 1b (Combination with Nivolumab) ECOG performance status of 0 or 1 at study entry and an estimated life expectancy of at least 3 months.
5. 5. Phase 1 (DF6002 Monotherapy) and Phase 1b (Combination with Nivolumab) Clinical or radiological evidence of disease.
6. 6. Phase 1/1b Safety PK/PD Expansion CohortSigned written informed consent.
7. 7. Phase 1/1b Safety PK/PD Expansion Cohort Male or female patients aged ≥ 18 years.
8. 8. Phase 1/1b Safety PK/PD Expansion Cohort ECOG performance status of 0 or 1 at study entry and an estimated life expectancy of at least 3 months.
9. 9. Phase 1/1b Safety PK/PD Expansion Cohort Measurable disease, as determined by the Investigator using RECIST, version 1.1.
10. 10. Phase 1/1b Safety PK/PD Expansion Cohort Agrees to undergo a pre-treatment biopsy and another biopsy while on treatment
11. 11. Phase 2, Advanced Melanoma (Cohort 2A and 2C) Signed written informed consent.
12. 12. Phase 2, Advanced Melanoma (Cohort 2A and 2C) Male or female patients aged ≥18 years.
13. 13. 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.
14. 14. Phase 2, Advanced Melanoma (Cohort 2A and 2C) PD-L1 status must be documented if available.
15. 15. 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.
16. 16. Phase 2 Non-Small Cell Lung Cancer (Cohort 2B and 2D) Signed written informed consent.
17. 17. Phase 2 Non-Small Cell Lung Cancer (Cohort 2B and 2D) Male or female patients aged ≥18 years.
18. 18. 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.
19. 19. Phase 2 Non-Small Cell Lung Cancer (Cohort 2B and 2D)Participants must have recurrent or progressive disease during or after platinum doublet- based chemotherapy or at least two prior lines of systemic therapy for advanced or metastatic disease. OR must have recurrent or progressive disease within 6 months after completing platinum-based chemotherapy for local disease
20. 20. Phase 2 Non-Small Cell Lung Cancer (Cohort 2B and 2D) Participants must have received and progressed on or after anti-PD-(L)1 therapy, if available.

Exclusion criteria 10

1. 1. Concurrent treatment with a non-permitted drug (see Protocol Section 9.6.2).
2. 2. Prior treatment with rhIL2 or with any drug containing an IL2 or IL12 moiety.
3. 3. 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 DF6002.
4. 4. 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.
5. 5. Rapidly progressive disease.
6. 6. 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.
7. 7. Patients with adrenal insufficiency requiring hormone replacement will be excluded from the “3+3” dose escalation.
8. 8. 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.
9. 9. Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
10. 10. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary endpoints in Phase 1/1b are: Occurrence of DLTs during the first 3 weeks of treatment.
2. The primary endpoints in Phase 2 are, for each cohort: Confirmed ORR, per RECIST 1.1, as adjudicated by an IERC.

Secondary endpoints 18

1. 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. 2. Phase 1/1b Change from baseline in laboratory parameters, electrocardiograms (ECGs), vital signs, and Eastern Cooperative Oncology Group (ECOG) performance status.
3. 3. Phase 1/1b DOR according to RECIST 1.1, per Investigator assessment.
4. 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. 5. Phase 1/1b BOR, according to RECIST 1.1, per Investigator assessment.
6. 6. Phase 1/1b CBR according to RECIST 1.1, per Investigator assessment.
7. 7. Phase 1/1bThe confirmed ORR, per RECIST 1.1, per investigator assessment.
8. 8. Phase 2 Number, severity, and duration of TEAEs for all dose groups/indications according to the NCI-CTCAE v5.0.
9. 9. Phase 2 Change from baseline in laboratory parameters, ECGs, vital signs, and ECOG performance status.
10. 10. Phase 2 BOR according to RECIST 1.1, per Investigator assessment.
11. 11. Phase 2 PFS according to RECIST 1.1, per Investigator assessment
12. 12. Phase 2 CBR according to RECIST 1.1, per Investigator assessment
13. 13. Phase 2 DOR according to RECIST 1.1, per Investigator assessment
14. 14. Phase 2 CBR according to RECIST 1.1, per IERC.
15. 15. Phase 2 PFS according to RECIST 1.1, per IERC.
16. 16. Phase 2 DOR according to RECIST 1.1, per IERC.
17. 17. Phase 2 Unconfirmed response after 4 cycles according to RECIST 1.1.
18. 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).

Investigational products

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

Test 1

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

Sean Rossi

Public contact point

Organisation

Dragonfly Therapeutics Inc.

Contact name

Sean Rossi

Third parties 4

Locations

2 EU/EEA countries · 9 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 18 files

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

Application history

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