Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Irvine, California and other locations
Dates
study started
estimated completion

Description

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.

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

Keywords

Solid Tumor, Adult HER-2 NK Cell Immunotherapy Metastatic Breast Cancer Urothelial Bladder Cancer Neoplasms Paclitaxel Nivolumab Nab paclitaxel Monotherapy DF1001 Dose Escalation Monotherapy DF1001 PK/PD Expansion Monotherapy DF1001 Expansion in Urothelial Bladder Cancer Monotherapy DF1001 Expansion in Metastatic Breast Cancer Monotherapy DF1001 Expansion in HER-2 High Expressing Cancers

Eligibility

You can join if…

Open to people ages 18 years and up

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.

You CAN'T join if...

  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.

  1. 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.
  2. Rapidly progressive disease.
  3. Active or history of central nervous system (CNS) metastases.
  4. Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
  5. 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).
  6. 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.
  7. 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).
  8. . Persisting toxicity related to prior therapy > Grade 1 NCI-CTCAE v5.0, however alopecia and sensory neuropathy ≤ Grade 2 is acceptable.
  9. . Pregnancy or lactation in females during the study.
  10. . Known alcohol or drug abuse.
  11. . Serious cardiac illness
  12. . NYHA III of IV heart failure or systolic dysfunction (LVEF < 55%)
  13. . High-risk uncontrolled arrhythmias ie, tachycardia with a heart rate > 100/min at rest
  14. . 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)
  15. . Angina pectoris requiring anti-anginal medication
  16. . Clinically significant valvular heart disease
  17. . Evidence of transmural infarction on ECG
  18. . Poorly controlled hypertension (defined by: systolic > 180 mm Hg or diastolic > 100 mm Hg)
  19. . 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.
  20. . Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
  21. . All other significant diseases (e.g., inflammatory bowel disease), which, in the opinion of the Investigator, might impair the patient's ability to participate
  22. . Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  23. . Legal incapacity or limited legal capacity.
  24. . 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.

Locations

  • University of California Irvine Medical Center accepting new patients
    Irvine California 92868 United States
  • University of Southern California accepting new patients
    Los Angeles California 90033 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Dragonfly Therapeutics
ID
NCT04143711
Phase
Phase 1/2
Study Type
Interventional
Last Updated