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Study of DF1001 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04143711
Recruitment Status : Recruiting
First Posted : October 29, 2019
Last Update Posted : February 12, 2020
Sponsor:
Information provided by (Responsible Party):
Dragonfly Therapeutics

Brief Summary:
DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells. The study will occur in two phases. The first phase will be a dose escalation phase, enrolling patients with various types of solid tumors that express human epidermal growth factor receptor 2 (HER2). The second phase will include a dose expansion using the best dose selected from the first phase of the study. Multiple cohorts will be opened with eligible patients having either selected solid tumors, or solid tumors expressing high levels of HER2. A combination therapy cohort of DF1001 and pembrolizumab will also be opened for enrollment.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: DF1001 Drug: Pembrolizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, First-In-Human, Multi-Part, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF1001 in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications
Actual Study Start Date : November 11, 2019
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Monotherapy DF1001 Dose Escalation
Dose escalation cohorts of DF1001 in sequential ascending order.
Drug: DF1001
Immunotherapy agent targeting NK cells.

Experimental: Monotherapy DF1001 PK/PD Expansion
Expansion cohorts of monotherapy DF1001 in multiple dose levels after evaluation for safety in Monotherapy Dose Escalation arm. Additional pharmacokinetic (PK) and pharmacodynamic (PD) samples included in this arm.
Drug: DF1001
Immunotherapy agent targeting NK cells.

Experimental: Monotherapy DF1001 Expansion in Urothelial Bladder Cancer
Monotherapy expansion cohort enrolling up to 40 patients with urothelial bladder cancer using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.
Drug: DF1001
Immunotherapy agent targeting NK cells.

Experimental: Monotherapy DF1001 Expansion in Metastatic Breast Cancer
Monotherapy expansion cohort enrolling up to 40 patients with metastatic breast cancer using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.
Drug: DF1001
Immunotherapy agent targeting NK cells.

Experimental: Monotherapy DF1001 Expansion in HER-2 High Expressing Cancers
Monotherapy expansion cohort enrolling up to 40 patients with solid tumors showing documented high levels HER-2 expression using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.
Drug: DF1001
Immunotherapy agent targeting NK cells.

Experimental: Combination Therapy with DF1001 and Pembrolizumab
Combination dose escalation of DF1001 in combination with a PD-1 checkpoint inhibitor in patients with select solid tumors.
Drug: DF1001
Immunotherapy agent targeting NK cells.

Drug: Pembrolizumab
Anti-PD-1 immunotherapy agent




Primary Outcome Measures :
  1. Assessment of number of dose limiting toxicities experienced on study as defined per criteria in the study protocol [ Time Frame: First 3 weeks of treatment for each subject. ]
    To assess the number of adverse events experienced during the study that meet dose limiting toxicity criteria per the study protocol.

  2. Assess Overall Response Rate [ Time Frame: Through 90 days after completion of the study, an average of 1 year. ]
    To assess the Overall Response Rate (ORR) per RECIST version 1.1 criteria.


Secondary Outcome Measures :
  1. Serum concentrations of DF1001 will be determined at various time points [ Time Frame: From start of treatment up through 28 days after last treatment. ]
    Concentration vs time of DF1001 will be measured using blood samples taken a various time points on study

  2. Evaluation of DF1001 immunogenicity [ Time Frame: Every 3 weeks up to 28 days after last treatment. ]
    Evaluate the immunogenicity of DF1001 by measuring the number of patients developing anti-DF1001 antibodies

  3. Assess Best Overall Response [ Time Frame: Through 90 days after completion of the study, an average of 1 year. ]
    To assess Best Overall Response (BOR)

  4. Assess Duration of Response [ Time Frame: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months ]
    To assess Duration of Response (DOR) of DF1001

  5. Assess Progression Free Survival (PFS) [ Time Frame: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months ]
    To assess Progression Free Survival (PFS) for DF1001

  6. Assess Overall Survival (OS) time. [ Time Frame: Time from enrollment in the study until death, measured up to 2 years after last treatment on study. ]
    To assess Overall Survival (OS)

  7. Assess number of adverse events observed during treatment with DF1001 in combination with Pembrolizumab [ Time Frame: Screening visit up to 28 days after last treatment on study. ]
    To assess the safety of DF1001 in Combination therapy with pembrolizumab by measuring Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: General (applies to all cohorts)

  1. Signed written informed consent.
  2. Male or female patients aged ≥ 18 years.
  3. Histologically or cytologically proven locally advanced or metastatic solid tumors. Primary tumor must have documented HER2 expression by immunohistochemistry.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry and an estimated life expectancy of at least 3 months.
  5. Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 55% measured by echocardiography (preferred) or multigated acquisition (MUGA) scan.
  6. Adequate hematological function.
  7. Adequate hepatic function.
  8. Adequate renal function.
  9. Effective contraception for women of child bearing potential (WOCBP) patients as defined by World Health Organization (WHO) guidelines for 1 "highly effective" method or 2 "effective" methods.

Inclusion Criteria: Dose Escalation

  1. Evidence of objective disease, but participation does not require a measurable lesion.
  2. Archived tumor biopsy available

Inclusion Criteria: Safety/PK/PD Expansion Cohorts

  1. Fresh tumor biopsy must be obtained during the screening window
  2. HER2 by immunohistochemistry (IHC)

Inclusion Criteria: Urothelial Bladder Cancer Expansion Cohort

  1. Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary urothelial, urethra).
  2. Patients must have radiographic disease progression after their last line of therapy.
  3. Patients must have received one (and no more than one) platinum-containing regimen (eg, platinum plus another agent such as gemcitabine, methotrexate, vinblastine, doxorubicin, etc.) for inoperable locally advanced or metastatic urothelial carcinoma with radiographic progression or with recurrent disease
  4. Patients must have received treatment with a checkpoint inhibitor (CPI) (i.e., anti-PD-1 or anti-PD-L1), with radiographic progression.
  5. Patients must have expression of HER2 by IHC.
  6. A fresh tumor biopsy must be obtained during the screening window

Inclusion Criteria: Metastatic Breast Cancer (MBC) Expansion Cohort

  1. Patients must have histologically confirmed MBC.
  2. Patients must have received no more than 3 prior lines of cytotoxic therapy for metastatic disease.
  3. Patients must have received a taxane and an anthracycline unless anthracycline is contraindicated.
  4. Patients must have HER2 expression by IHC
  5. Patients must have progressed (radiographically) after their last line of systemic therapy.
  6. A fresh tumor biopsy must be obtained during the screening window

Inclusion Criteria: HER-2 High Basket Cohort

  1. Patients with any solid tumor except breast cancer or gastric cancer HER2 high expression by IHC
  2. Patients must have received at least one prior line of an approved or established therapy.
  3. A fresh tumor biopsy must be obtained during the screening window

Inclusion Criteria: Combination Therapy with Pembrolizumab

  1. Patients must be eligible to receive pembrolizumab per its label for a malignancy of epithelial origin.
  2. A fresh tumor biopsy must be obtained during the screening window

Exclusion Criteria:

  1. Concurrent treatment with a non-permitted drug as in Non-Permitted Medicines and Therapies section. Previous treatment with drugs that specifically target the HER2 pathway (mAb or tyrosine kinase inhibitor [TKI]) is acceptable providing washout period (4 weeks for mAbs or protein therapeutics and 2 weeks for a TKI).
  2. 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 steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of study treatment. Short-term administration of systemic steroids (i.e., for allergic reactions or the management of immune-related adverse events [irAEs]) is allowed.

    Note: Patients receiving bisphosphonates are eligible provided treatment was initiated at least 14 days before the first dose of DF1001.

  3. Previous malignant disease other than the target malignancy to be investigated in this study within the last 3 years, with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ.
  4. Rapidly progressive disease.
  5. Active or history of central nervous system (CNS) metastases.
  6. Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
  7. 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).
  8. Preexisting autoimmune disease (except for patients with vitiligo) needing treatment with systemic immunosuppressive agents for more than 28 days within the last 3 years or clinically relevant immunodeficiencies (eg, dys-gammaglobulinemia or congenital immunodeficiencies), or fever within 7 days of Day 1.
  9. Known severe hypersensitivity reactions to mAbs (≥ Grade 3 NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly controlled asthma).
  10. Persisting toxicity related to prior therapy > Grade 1 NCI-CTCAE v5.0, however alopecia and sensory neuropathy ≤ Grade 2 is acceptable.
  11. Pregnancy or lactation in females during the study.
  12. Known alcohol or drug abuse.
  13. Serious cardiac illness
  14. All other significant diseases (e.g., inflammatory bowel disease), which, in the opinion of the Investigator, might impair the patient's ability to participate
  15. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  16. Legal incapacity or limited legal capacity.
  17. Incapable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04143711


Contacts
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Contact: Sean Rossi 671-588-0086 SeanR@Dragonflytx.com

Locations
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United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Howard Safran, M.D.    401-444-3234    ASchumacher@Lifespan.org   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Vivek Subbiah, M.D.    713-563-1930    vsubbiah@mdanderson.org   
Sponsors and Collaborators
Dragonfly Therapeutics
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Responsible Party: Dragonfly Therapeutics
ClinicalTrials.gov Identifier: NCT04143711    
Other Study ID Numbers: DF1001-001
First Posted: October 29, 2019    Key Record Dates
Last Update Posted: February 12, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dragonfly Therapeutics:
HER-2
NK Cell
Immunotherapy
Metastatic Breast Cancer
Urothelial Bladder Cancer
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents