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BRIEF TITLE: 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

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


  • Org Study ID: DF1001-001
  • Secondary ID:
  • NCT ID: NCT04143711
  • NCT Alias:
  • Sponsor: Dragonfly Therapeutics - Industry
  • Source: 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). 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.

Overal Status Start Date Phase Study Type
Recruiting November 11, 2019 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Assessment of number of dose limiting toxicities experienced on study as defined per criteria in the study protocol

Primary Outcome 1 - Time Frame: First 3 weeks of treatment for each subject.

Primary Outcome 2 - Measure: Assess Overall Response Rate

Primary Outcome 2 - Time Frame: Through 90 days after completion of the study, an average of 1 year.

Condition:

  • Solid Tumor, Adult

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: "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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Sean Rossi

Phone: 671-588-0086

Email: Sean.Rossi@Dragonflytx.com

Locations

Facility Status Contact
University of California Irvine Medical Center
Irvine, California 92868
United States
Recruiting Jennifer Valerin, M.D.

University of Southern California
Los Angeles, California 90033
United States
Recruiting Anthony El-Khoueiry, M.D.

Sharp Healthcare
San Diego, California 92123
United States
Recruiting Charles Redfern, M.D.

University of Michigan
Ann Arbor, Michigan 48109
United States
Recruiting Ulka Vaishampayan, M.D.

Henry Ford Health System
Detroit, Michigan 48202
United States
Recruiting Shirish Gadgeel, M.D.

Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York 10023
United States
Recruiting Matthew Galsky, M.D.

University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106
United States
Recruiting Debora Bruno, M.D.

Rhode Island Hospital
Providence, Rhode Island 02903
United States
Recruiting Howard Safran, M.D.

Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37232
United States
Recruiting Jordan Berlin, M.D.

MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting Vivek Subbiah, M.D.