Clinical Trials /

Study of DF1001 in Patients With Advanced Solid Tumors

NCT04143711

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of DF1001 in Patients With Advanced Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: DF1001-001
  • NCT ID: NCT04143711

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
DF1001Monotherapy DF1001 Dose Escalation
PembrolizumabCombination Therapy with DF1001 and Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Monotherapy DF1001 Dose EscalationExperimentalDose escalation cohorts of DF1001 in sequential ascending order.
  • DF1001
Monotherapy DF1001 PK/PD ExpansionExperimentalExpansion 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.
  • DF1001
Monotherapy DF1001 Expansion in Urothelial Bladder CancerExperimentalMonotherapy 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.
  • DF1001
Monotherapy DF1001 Expansion in Metastatic Breast CancerExperimentalMonotherapy 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.
  • DF1001
Monotherapy DF1001 Expansion in HER-2 High Expressing CancersExperimentalMonotherapy 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.
  • DF1001
Combination Therapy with DF1001 and PembrolizumabExperimentalCombination dose escalation of DF1001 in combination with a PD-1 checkpoint inhibitor in patients with select solid tumors.
  • DF1001
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:To assess the number of adverse events experienced during the study that meet dose limiting toxicity criteria per the study protocol.

Secondary Outcome Measures

Measure:Serum concentrations of DF1001 will be determined at various time points
Time Frame:From start of treatment up through 28 days after last treatment.
Safety Issue:
Description:Concentration vs time of DF1001 will be measured using blood samples taken a various time points on study
Measure:Evaluation of DF1001 immunogenicity
Time Frame:Every 3 weeks up to 28 days after last treatment.
Safety Issue:
Description:Evaluate the immunogenicity of DF1001 by measuring the number of patients developing anti-DF1001 antibodies
Measure:Assess Best Overall Response
Time Frame:Through 90 days after completion of the study, an average of 1 year.
Safety Issue:
Description:To assess Best Overall Response (BOR)
Measure: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
Safety Issue:
Description:To assess Duration of Response (DOR) of DF1001
Measure: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
Safety Issue:
Description:To assess Progression Free Survival (PFS) for DF1001
Measure: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.
Safety Issue:
Description:To assess Overall Survival (OS)
Measure: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.
Safety Issue:
Description: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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dragonfly Therapeutics

Trial Keywords

  • HER-2
  • NK Cell
  • Immunotherapy
  • Metastatic Breast Cancer
  • Urothelial Bladder Cancer

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