Study of DF1001 in Patients With Advanced Solid Tumors

NCT04143711 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: DF1001-001
• Study Type: interventional
• Target: 270
• Locations: 6 countries
• Sites: 44

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). 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 HER2 activated non-small cell lung cancer, hormone receptor (HR) positive HER2 negative metastatic breast cancer, or HER2 positive metastatic breast cancer. DF1001-001 will be administered as monotherapy or in combination; combinations are DF1001 + nivolumab, DF1001 + Nab paclitaxel, and DF1001 + sacituzumab govitecan-hziy.

Conditions

Solid Tumor, Adult

Keywords

HER-2; NK Cell; Immunotherapy; Metastatic Breast Cancer; Non-small Cell Lung Cancer; Erbb2; DF1001; Sacituzumab Govitecan-hziy

Outcome Measures

Primary Outcomes (5)

• 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 3 weeks of treatment for each subject.

• Assess Overall Response Rate

  To assess the confirmed Overall Response Rate (ORR) per RECIST version 1.1 criteria by Investigator Assessment in the Efficacy Phase.

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

• Assess number of adverse events observed during treatment with DF1001 in combination with Nivolumab

  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

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

• Assess number of adverse events observed during treatment with DF1001 in combination with Nab paclitaxel

  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

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

• Assess number of adverse events observed during treatment with DF1001 in combination with Sacituzumab govitecan-hziy

  To assess the safety of DF1001 in Combination therapy with Sacituzumab govitecan-hziy 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

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

Secondary Outcomes (7)

• Evaluation of DF1001 Pharmacokinetics

  From start of treatment up through 28 days after last treatment.

• Evaluation of DF1001 Immunogenicity

  Every 3 weeks up to 28 days after last treatment.

• Assess Overall Survival (OS) Time.

  Time from enrollment in the study until death, measured up to 2 years after last treatment on study.

• Assess Overall Response Rate by Investigator Assessment.

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

• Assess Duration of Response by Investigator Assessment.

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

Study Arms (22)

Monotherapy DF1001 Dose Escalation

EXPERIMENTAL

Dose escalation cohorts of DF1001 in sequential ascending order.

Drug: DF1001

Monotherapy DF1001 Safety/PK/PD Expansion

EXPERIMENTAL

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.

Drug: DF1001

Monotherapy DF1001 Expansion in Urothelial Bladder Cancer

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20 patients with urothelial bladder cancer using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Drug: DF1001

Monotherapy DF1001 Expansion in Metastatic Breast Cancer (HER2 Low)

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20 patients with metastatic breast cancer with documented low expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Drug: DF1001

Monotherapy DF1001 Expansion in Cancers with Erbb2 Amplification

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 40 patients with solid tumors showing documented erbb2 amplification using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Drug: DF1001

Combination Therapy with DF1001 and Nivolumab

EXPERIMENTAL

Combination dose escalation of DF1001 in combination with nivolumab in patients with select solid tumors.

Drug: DF1001; Drug: Nivolumab

Combination Therapy with DF1001 and Nab-paclitaxel

EXPERIMENTAL

Combination dose escalation of DF1001 in combination with nab-paclitaxel in patients with select solid tumors.

Drug: DF1001; Drug: Nab paclitaxel

Combination Therapy with DF1001 and Nivolumab Safety/PK/PD Expansion

EXPERIMENTAL

Expansion cohort of DF1001 in combination with nivolumab after evaluation for safety in the Combination Therapy with DF1001 and nivolumab Dose Escalation arm. Additional pharmacokinetic (PK) and pharmacodynamic (PD) samples included in this arm.

Drug: DF1001; Drug: Nivolumab

Combination Therapy with DF1001 and Nab-paclitaxel Safety/PK/PD Expansion

EXPERIMENTAL

Expansion cohort of DF1001 in combination with nab-paclitaxel after evaluation for safety in the Combination Therapy with DF1001 and nab-paclitaxel Dose Escalation arm. Additional pharmacokinetic (PK) and pharmacodynamic (PD) samples included in this arm.

Drug: DF1001; Drug: Nab paclitaxel

Combination Therapy with DF1001 and Nivolumab Expansion in Urothelial Bladder Cancer

EXPERIMENTAL

Combination therapy with DF1001 and nivolumab expansion cohort enrolling up to 20 patients with urothelial bladder cancer using the recommended phase 2 dose (RP2D) identified in the Combination Therapy with DF1001 and nivolumab arm.

Drug: DF1001; Drug: Nivolumab

Monotherapy DF1001 Expansion in Metastatic Breast Cancer (HER2 High)

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20 patients with metastatic breast cancer with documented high expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Drug: DF1001

Monotherapy DF1001 Expansion in NSCLC

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20 patients with non-small cell lung cancer with documented erbb2 amplification using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Drug: DF1001

Combination Therapy with DF1001 and Nivolumab Expansion in NSCLC

EXPERIMENTAL

Combination therapy with DF1001 and nivolumab expansion cohort enrolling up to 20 patients with non-small cell lung cancer with documented low expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Combination Therapy with DF1001 and nivolumab arm.

Drug: DF1001; Drug: Nivolumab

Monotherapy DF1001 Expansion in Gastric Cancer

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20 patients with gastric cancer with documented high expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Drug: DF1001

Combination Therapy with DF1001 and Nivolumab Expansion in Gastric Cancer

EXPERIMENTAL

Combination therapy with DF1001 and nivolumab expansion cohort enrolling up to 20 patients with gastric cancer with documented low expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Combination Therapy with DF1001 and nivolumab arm.

Drug: DF1001; Drug: Nivolumab

Monotherapy DF1001 Expansion in Esophageal Cancer

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20 patients with esophageal cancer with documented high expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Monotherapy Dose Escalation arm.

Drug: DF1001

Combination Therapy with DF1001 and Nivolumab Expansion in Esophageal Cancer

EXPERIMENTAL

Combination therapy with DF1001 and nivolumab expansion cohort enrolling up to 20 patients with esophageal cancer with documented low expression of HER2 using the recommended phase 2 dose (RP2D) identified in the Combination Therapy with DF1001 and nivolumab arm.

Drug: DF1001; Drug: Nivolumab

Monotherapy DF1001 Exploratory Efficacy Expansion in NSCLC

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20 patients with non-small cell lung cancer with documentation of HER2 activation.

Drug: DF1001

Combo Therapy with DF1001 and Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in NSCLC

EXPERIMENTAL

Combination therapy with DF1001 and sacituzumab govitecan-hziy cohort enrolling up to 20 patients, including safety lead-in, with non-small cell lung cancer with documentation of HER2 activation.

Drug: DF1001; Drug: Sacituzumab Govitecan-hziy

Monotherapy DF1001 Exploratory Efficacy Expansion in Metastatic Breast Cancer (HR+/HER2-)

EXPERIMENTAL

Monotherapy expansion cohort enrolling up to 20 patients with metastatic breast cancer with documentation of HR positive and HER2 negative expression.

Drug: DF1001

DF1001 with Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in Breast Cancer (HER2+)

EXPERIMENTAL

Combination therapy with DF1001 and sacituzumab govitecan-hziy cohort enrolling up to 40 patients, including safety lead-in, with metastatic breast cancer with documentation of HER2 positive expression.

Drug: DF1001; Drug: Sacituzumab Govitecan-hziy

DF1001 with Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in Breast Cancer (HR+/HER2-)

EXPERIMENTAL

Combination therapy with DF1001 and sacituzumab govitecan-hziy cohort enrolling up to 40 patients, including safety lead-in, with metastatic breast cancer with documentation of HR positive and HER2 negative expression.

Drug: DF1001; Drug: Sacituzumab Govitecan-hziy

Interventions

DF1001 DRUG

Immunotherapy agent targeting NK cells.

Combination Therapy with DF1001 and Nab-paclitaxel; Combination Therapy with DF1001 and Nab-paclitaxel Safety/PK/PD Expansion; Combination Therapy with DF1001 and Nivolumab; Combination Therapy with DF1001 and Nivolumab Expansion in Esophageal Cancer; Combination Therapy with DF1001 and Nivolumab Expansion in Gastric Cancer; Combination Therapy with DF1001 and Nivolumab Expansion in NSCLC; Combination Therapy with DF1001 and Nivolumab Expansion in Urothelial Bladder Cancer; Combination Therapy with DF1001 and Nivolumab Safety/PK/PD Expansion; Combo Therapy with DF1001 and Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in NSCLC; DF1001 with Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in Breast Cancer (HER2+); DF1001 with Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in Breast Cancer (HR+/HER2-); Monotherapy DF1001 Dose Escalation; Monotherapy DF1001 Expansion in Cancers with Erbb2 Amplification; Monotherapy DF1001 Expansion in Esophageal Cancer; Monotherapy DF1001 Expansion in Gastric Cancer; Monotherapy DF1001 Expansion in Metastatic Breast Cancer (HER2 High); Monotherapy DF1001 Expansion in Metastatic Breast Cancer (HER2 Low); Monotherapy DF1001 Expansion in NSCLC; Monotherapy DF1001 Expansion in Urothelial Bladder Cancer; Monotherapy DF1001 Exploratory Efficacy Expansion in Metastatic Breast Cancer (HR+/HER2-); Monotherapy DF1001 Exploratory Efficacy Expansion in NSCLC; Monotherapy DF1001 Safety/PK/PD Expansion

Nivolumab DRUG

Anti-PD-1 immunotherapy agent

Combination Therapy with DF1001 and Nivolumab; Combination Therapy with DF1001 and Nivolumab Expansion in Esophageal Cancer; Combination Therapy with DF1001 and Nivolumab Expansion in Gastric Cancer; Combination Therapy with DF1001 and Nivolumab Expansion in NSCLC; Combination Therapy with DF1001 and Nivolumab Expansion in Urothelial Bladder Cancer; Combination Therapy with DF1001 and Nivolumab Safety/PK/PD Expansion

Nab paclitaxel DRUG

A chemotherapy treatment combining paclitaxel with albumin

Combination Therapy with DF1001 and Nab-paclitaxel; Combination Therapy with DF1001 and Nab-paclitaxel Safety/PK/PD Expansion

Sacituzumab Govitecan-hziy DRUG

A Trop-2 (Tumor-associated calcium signal transducer 2) directed antibody and topoisomerase inhibitor drug conjugate

Combo Therapy with DF1001 and Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in NSCLC; DF1001 with Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in Breast Cancer (HER2+); DF1001 with Sacituzumab Govitecan-hziy Exploratory Efficacy Expansion in Breast Cancer (HR+/HER2-)

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.
• Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 55% measured by echocardiography (preferred) or multigated acquisition (MUGA) scan.
• Adequate hematological function.
• Adequate hepatic function.
• Adequate renal function.
• 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.
• Have progression of unresectable locally advanced or metastatic NSCLC after last systemic therapy (as confirmed by investigator) or be intolerant of last systemic therapy.
• Have HER2 overexpression status (IHC 2+ or 3+), or ERBB2 amplification, or HER2 activating mutation
• Have recurrent or progressive disease during or after platinum doublet-based chemotherapy.
• Have received and progressed on or after anti-PD-(L)1 therapy.
• Documented evidence of HR+ metastatic breast cancer
• Documented evidence of HER2- status.
• Disease progression or recurrence after prior therapy.

You may not qualify if:

• 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 or 5 half-lives before the start of study treatment. Note: Patients receiving bisphosphonates are eligible provided treatment was initiated at least 14 days before the first dose of DF1001.
• 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.
• Rapidly progressive disease.
• Active or history of central nervous system (CNS) metastases.
• 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).
• 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.
• 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).
• Persisting toxicity related to prior therapy \> Grade 1 NCI-CTCAE v5.0, however alopecia and sensory neuropathy ≤ Grade 2 is acceptable.
• Pregnancy or lactation in females during the study.
• Known alcohol or drug abuse.
• Serious cardiac illness
• NYHA III of IV heart failure or systolic dysfunction (LVEF \< 55%)
• High-risk uncontrolled arrhythmias ie, tachycardia with a heart rate \> 100/min at rest
• 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)

Sponsors & Collaborators

• Dragonfly Therapeutics: lead

Study Sites (44)

University of California Irvine Medical Center

Irvine, California, 92868, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Sharp Healthcare

San Diego, California, 92123, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Westwood, Kansas, 66205, United States

Location

Louisiana State University

New Orleans, Louisiana, 70112, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, 10023, United States

Location

Montefiore Einstein Center for Cancer Care

The Bronx, New York, 10461, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Multicare Health System Tacoma General Hospital

Tacoma, Washington, 98405, United States

Location

University of Wisconsin

Madison, Wisconsin, 53715, United States

Location

Centre Hospitalier de l'Ardenne

Arlon, 6700, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

Domaine Universitaire du Sart Tilman; CHU de Liege

Liège, 4000, Belgium

Location

Rigshospitalet

Copenhagen, Capital Region, 2100, Denmark

Location

Herlev og Gentofte Hospital

Herlev, 2730, Denmark

Location

Institut Curie

Paris, Paris, 75005, France

Location

Groupe Hospitalier Saint Andre

Bordeaux, 33000, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Institut Regional du Cancer de Montepelier

Montpellier, France

Location

ICO - Site Rene Gauducheau

Saint-Herblain, 44805, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Amsterdam University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Maasticht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Radboud University Nijmegen

Nijmegen, 6525 EZ, Netherlands

Location

Erasmus University Medical Center

Rotterdam, 3015 ZH, Netherlands

Location

UMC Utrecht

Utrecht, 3508 GA, Netherlands

Location

Inje University Haeundae Paik Hospital

Busan, South Korea

Location

National Cancer Center

Goyang-si, South Korea

Location

Ajou University Hospital

Gyeonggi-do, South Korea

Location

CHA Bundang Medical Center, CHA University

Gyeonggi-do, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Taxes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations

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, 2019
• First Posted: October 29, 2019
• Study Start: November 11, 2019
• Primary Completion: December 5, 2025
• Study Completion: December 5, 2025
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

DK (2); KR (9); FR (8); US (16); BE (3); NL (6)