Study of DF9001 in Patients With Advanced Solid Tumors

NCT05597839 | Completed Phase 1 FDA Drug

• 3 other identifiers: DF9001-001KEYNOTE-F92MK-3475-F92
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 17

Brief Summary

DF9001-001 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 epidermal growth factor receptor (EGFR). 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 selected solid tumors (monotherapy and in combination with pembrolizumab).

Conditions

Solid Tumor, Adult

Keywords

EGFR; NK Cell; Immunotherapy; Non-Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Renal Cell Carcinoma; pembrolizumab; KEYTRUDA®

Outcome Measures

Primary Outcomes (4)

• Number, severity, and duration of treatment-related adverse events (TRAEs) according to NCI-CTCAE v5.0.

  To assess the safety of DF9001 by measuring Number of subjects with Treatment-Related Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

  Screening visit up to 28 days after last treatment on the study.

• Number of patients with AEs and TRAEs.

  To assess the safety of DF9001 by measuring Number of subjects with Treatment-Related Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

  Screening visit up to 28 days after last treatment on the study.

• Assessment of number of dose limiting toxicities experienced on study as defined per criteria in the study protocol

  To assess the number of adverse events experienced during the study that meet dose limiting toxicity criteria per the study protocol.

  First 4 weeks of treatment for each subject.

• Assess Overall Response Rate

  To assess the Overall Response Rate (ORR) per RECIST 1.1 criteria.

  Through 90 days after completion of the study, an average of 1 year.

Secondary Outcomes (4)

• Serum concentrations of DF9001 will be determined at various time points.

  From start of treatment up through 7 days after the decision to stop study treatment.

• Assess the best overall response (BOR) per RECIST v1.1.

  Through 90 days after completion of the study, an average of 1 year.

• Assess the duration of response (DOR) per RECIST v1.1.

  From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months.

• Assess progression-free survival (PFS) for DF9001 per RECIST v1.1.

  From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months.

Study Arms (6)

Monotherapy DF9001 Dose Escalation

EXPERIMENTAL

Dose escalation cohorts of DF9001 in sequential ascending order.

Drug: DF9001

Monotherapy DF9001 Expansion in Head and Neck Squamous Cell Carcinoma

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20-40 patients with head and neck squamous cell carcinoma (HNSCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Drug: DF9001

Monotherapy DF9001 Expansion in Non-small Cell Lung Cancer

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20-40 patients with Non-small cell lung cancer (NSCLC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Drug: DF9001

Combination Expansion of DF9001 and pembrolizumab in Head and Neck Squamous Cell Carcinoma

EXPERIMENTAL

Combination expansion cohort using DF9001 and a PD-1 checkpoint inhibitor enrolling 20-40 patients with head and neck squamous cell carcinoma (HNSCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Drug: DF9001; Drug: KEYTRUDA® (pembrolizumab)

Combination Expansion of DF9001 and pembrolizumab in Renal Cell Carcinoma

EXPERIMENTAL

Combination expansion cohort using DF9001 and a PD-1 checkpoint inhibitor enrolling 20-40 patients with renal cell carcinoma (RCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Drug: DF9001; Drug: KEYTRUDA® (pembrolizumab)

Monotherapy DF9001 Expansion in Renal Cell Carcinoma

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20-40 patients with renal cell carcinoma (RCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.

Drug: DF9001

Interventions

DF9001 DRUG

Immunotherapy agent targeting NK cells.

Combination Expansion of DF9001 and pembrolizumab in Head and Neck Squamous Cell Carcinoma; Combination Expansion of DF9001 and pembrolizumab in Renal Cell Carcinoma; Monotherapy DF9001 Dose Escalation; Monotherapy DF9001 Expansion in Head and Neck Squamous Cell Carcinoma; Monotherapy DF9001 Expansion in Non-small Cell Lung Cancer; Monotherapy DF9001 Expansion in Renal Cell Carcinoma

KEYTRUDA® (pembrolizumab) DRUG

Anti-PD-1 immunotherapy agent

Combination Expansion of DF9001 and pembrolizumab in Head and Neck Squamous Cell Carcinoma; Combination Expansion of DF9001 and pembrolizumab in Renal Cell Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent.
• Male or female patients aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry and an estimated life expectancy of at least 3 months.
• Adequate hematological function per protocol.
• Adequate hepatic function per protocol.
• Adequate renal function per protocol.
• Participation in the use of contraception during the study, and for 150 days after the last dose of study drug for women of child-bearing potential (WOCBP) and 30 days after the last dose of study drug for male patients, as defined by the Clinical Trial Facilitation Group (CTFG) guidelines.
• Histologically proven locally advanced or metastatic solid tumors of epithelial origin that (1) have squamous NSCLC or HNSCC, (2) has documented EGFR protein expression or EGFR amplification or polysomy in their medical history from previous testing, or (3) test positive for EGFR expression via archival or fresh biopsy tissue prior to study enrollment using a validated immunohistochemistry (IHC) assay.
• Evidence of objective disease, but participation does not require a measurable lesion.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Histologically documented relapsed or metastatic HNSCC. Primary tumor locations include oropharynx, oral cavity, hypopharynx, or larynx. Patients may not have a primary tumor site of nasopharynx (any histology).
• Patients must have radiographic disease progression while on or after having received both platinum-based or fluoropyrimidine-based chemotherapy and an anti-PD-(L)1 therapy, administered either concurrent or sequentially.
• Willing and able to provide the most recently available tissue blocks representing tumor biopsy obtained prior to treatment initiation. If recent tissue is not available, then a newly obtained baseline biopsy of an accessible tumor is required. Note that "recent" is defined as no intervening systemic anticancer therapies from the time of the last treatment of the prior therapy until screening for this trial.
• Willing to undergo on-treatment biopsies, if safe and medically feasible.
• Patients must have radiographic progression during treatment or after completing treatment for advanced (recurrent/unresectable/metastatic) disease or be intolerant to prior therapy.

You may not qualify if:

• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
• a. Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system (CNS) disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
• Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy \[except for palliative bone-directed radiotherapy, which is not a target lesion\], 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 or 5 half-lives of the drug (if known), whichever is shorter, before the start of study treatment. Short-term administration of systemic steroids (eg, for allergic reactions or the management of irAEs) is allowed. Note: Patients receiving bisphosphonate or denosumab are eligible, provided treatment was initiated at least 14 days before the first dose of DF9001.
• Previous malignant disease other than the target malignancy to be investigated in this study within the last 3 years. Exceptions (eg, basal or squamous cell carcinoma of the skin, or cervical carcinoma in situ) can be considered on a case-by-case basis, in consultation with the Medical Monitor.
• Life expectancy of less than 6 months.
• Receipt of any organ transplantation, including autologous or allogeneic stem-cell transplantation.
• 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). If HBsAg is negative and the anti-hepatitis B core antibody is positive, then hepatitis B viral DNA load must be undetectable.
• 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, dysgammaglobulinemia or congenital immunodeficiencies). Patients with a history of immune-related endocrinopathies (eg, hypothyroidism, type 1 diabetes mellitus \[TIDM\], and adrenal insufficiency) that are stable on hormone replacement therapy may be eligible for this study.
• Patients with a known medical history that may place them at risk of known toxicities of EGFR blockade.
• History of or ongoing keratitis, ulcerative keratitis, or corneal perforation.
• History of cardiopulmonary arrest unless this was caused by an acute, reversible etiology that is no longer present.
• History of or ongoing pulmonary fibrosis or interstitial lung disease.
• Known severe hypersensitivity reactions to mAbs (≥ Grade 3 of the NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly controlled asthma).
• Persisting toxicity related to prior therapy \>Grade 1 NCI-CTCAE v5.0; however, alopecia ≤Grade 2, endocrinopathies ≤Grade 2, and sensory neuropathy ≤ Grade 2 is acceptable.

Sponsors & Collaborators

• Dragonfly Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (17)

Banner MD Anderson

Gilbert, Arizona, 85234, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

UC Irvine Medical Center

Irvine, California, 92617, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Louisville Hospital

Louisville, Kentucky, 40202, United States

Location

Mayo Clinic Minnesota

Rochester, Minnesota, 55905, United States

Location

AMR Kansas City

Kansas City, Missouri, 64114, United States

Location

Rutgers

New Brunswick, New Jersey, 08903, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UMPC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 28, 2022
• Study Start: November 15, 2022
• Primary Completion: August 15, 2025
• Study Completion: August 15, 2025
• Last Updated: October 29, 2025

Record last verified: 2025-10

Locations

US (17)