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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 : March 22, 2022
Sponsor:
Information provided by (Responsible Party):
Dragonfly Therapeutics

Tracking Information
First Submitted Date  ICMJE October 18, 2019
First Posted Date  ICMJE October 29, 2019
Last Update Posted Date March 22, 2022
Actual Study Start Date  ICMJE November 11, 2019
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2019)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2021)
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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)
  • Assess number of adverse events observed during treatment with DF1001 in combination with nivolumab [ Time Frame: Screening visit up to 28 days after last treatment on study. ]
    To assess the safety of DF1001 in Combination therapy with nivolumab 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
  • Assess number of adverse events observed during treatment with DF1001 in combination with Nab paclitaxel [ Time Frame: Screening visit up to 28 days after last treatment on study. ]
    To assess the safety of DF1001 in Combination therapy with Nab paclitaxel 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2019)
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of DF1001 in Patients With Advanced Solid Tumors
Official Title  ICMJE 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
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). Two combination therapy cohorts will be opened for enrollment, DF1001 + nivolumab and DF1001 + Nab paclitaxel. 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor, Adult
Intervention  ICMJE
  • Drug: DF1001
    Immunotherapy agent targeting NK cells.
  • Drug: Nivolumab
    Anti-PD-1 immunotherapy agent
  • Drug: Nab paclitaxel
    A chemotherapy treatment combining paclitaxel with albumin
Study Arms  ICMJE
  • Experimental: Monotherapy DF1001 Dose Escalation
    Dose escalation cohorts of DF1001 in sequential ascending order.
    Intervention: Drug: DF1001
  • 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.
    Intervention: Drug: DF1001
  • 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.
    Intervention: Drug: DF1001
  • Experimental: Monotherapy DF1001 Expansion in Metastatic Breast Cancer
    Monotherapy expansion cohort enrolling up to 50 patients with metastatic breast cancer using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.
    Intervention: Drug: DF1001
  • 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.
    Intervention: Drug: DF1001
  • Experimental: Combination Therapy with DF1001 and nivolumab
    Combination dose escalation of DF1001 in combination with a PD-1 checkpoint inhibitor in patients with select solid tumors.
    Interventions:
    • Drug: DF1001
    • Drug: Nivolumab
  • Experimental: Combination Therapy with DF1001 and Nab paclitaxel
    Combination dose escalation of DF1001 in combination with a PD-L1 checkpoint inhibitor in patients with select solid tumors.
    Interventions:
    • Drug: DF1001
    • Drug: Nab paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 28, 2019)
220
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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: "3+3" Nivolumab Combination Cohort

  1. Eligible to receive nivolumab per its label for a malignancy of epithelial origin; or
  2. Have no standard therapy available, or standard therapy has failed, and must not have received nivolumab prior to joining the study.

Inclusion Criteria: "3+3" Nab paclitaxel Combination Cohort

  1. Eligible for treatment with nab paclitaxel. In this case, additional inclusion criteria include also no exposure to taxanes in the last 6 months; or
  2. Have tumor for which no standard therapy exists, or tumor for which standard therapy has failed. In this case, patients should also not have been treated with a taxane over the last 6 months.

Inclusion Criteria: Safety/PK/PD Expansion Cohorts

  1. Fresh tumor biopsy must be obtained during the screening window.
  2. HER2 by immunohistochemistry (IHC).
  3. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.

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.
  7. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.

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 ob tained 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. NYHA III of IV heart failure or systolic dysfunction (LVEF < 55%)
  15. High-risk uncontrolled arrhythmias ie, tachycardia with a heart rate > 100/min at rest
  16. Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade Atrioventricular block (AV-block; second-degree AV-block Type 2 [Mobitz 2] or third-degree AV-block)
  17. Angina pectoris requiring anti-anginal medication
  18. Clinically significant valvular heart disease
  19. Evidence of transmural infarction on ECG
  20. Poorly controlled hypertension (defined by: systolic > 180 mm Hg or diastolic > 100 mm Hg)
  21. Clinically relevant uncontrolled cardiac risk factors, clinically relevant pulmonary disease or any clinically relevant medical condition in the opinion of the Investigator that may limit participation in this study.
  22. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
  23. All other significant diseases (e.g., inflammatory bowel disease), which, in the opinion of the Investigator, might impair the patient's ability to participate
  24. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  25. Legal incapacity or limited legal capacity.
  26. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sean Rossi 671-588-0086 ext 7060 Sean.Rossi@Dragonflytx.com
Listed Location Countries  ICMJE Belgium,   Denmark,   France,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04143711
Other Study ID Numbers  ICMJE DF1001-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Dragonfly Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Dragonfly Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Dragonfly Therapeutics
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP