Dose Escalation of DF6002 in Patients With Advanced Solid Tumors and Expansion in Selected Indications

  • STATUS
    Recruiting
  • End date
    Dec 30, 2024
  • participants needed
    380
  • sponsor
    Dragonfly Therapeutics
Updated on 13 June 2021
Investigator
Sean Rossi
Primary Contact
Rhode Island Hospital (9.6 mi away) Contact
+6 other location
renal function
cancer
immunosuppressant
tyrosine
lymphoma
hodgkin's disease
immunosuppressive
monoclonal antibodies
systemic therapy
measurable disease
carcinoma
breast cancer
hepatitis
growth factor
squamous cell carcinoma
lung cancer
BRAF
major surgery
experimental drug
metastasis
progressive disease
esophageal cancer
pembrolizumab
ROS1
RET
HER2
EGFR
carcinoma in situ
pd-l1
programmed cell death 1 ligand 1
nivolumab
cancer treatment
neuropathy
cancer chemotherapy
solid tumour
alopecia
erbb2
autoimmune disease
squamous cell carcinoma of head and neck
braf inhibitor
asthma
renal function tests
interleukin 2
transitional cell carcinoma
platinum-based chemotherapy
advanced urothelial carcinoma
metastatic transitional cell carcinoma
metastatic urothelial carcinoma
immunomodulator
immunostimulants
immunomodulators
advanced renal cell carcinoma
endometrial carcinoma
kidney function test
advanced melanoma
lung carcinoma
cytokine therapy
immunologic adjuvant

Summary

This study is a Phase 1/2, open-label, dose-escalation study with a consecutive parallel-group efficacy expansion study, designed to determine the safety, tolerability, PK, pharmacodynamics, and preliminary anti-tumor activity of DF6002 as monotherapy and in combination with nivolumab.

Description

This study is a Phase 1/2, open-label, dose-escalation study with a consecutive parallel-group efficacy expansion study, designed to determine the safety, tolerability, PK, pharmacodynamics, and preliminary anti-tumor activity of DF6002 as monotherapy and in combination with nivolumab.

The study consists of 3 parts:

Phase 1: Dose-escalation as a monotherapy using a 3+3 design, with Phase 1 Cohort Expansion.

Phase 1b: Dose-escalation as a combination with nivolumab using a 3+3 design, with Phase 1b Cohort Expansion.

Phase 2: Efficacy Expansion using a group sequential design.

In Phase 2, DF6002 will be evaluated as a monotherapy in the following indications:

Cohort 2A: Advanced (unresectable or metastatic) melanoma.

Cohort 2B: Advanced (unresectable or metastatic) non-small cell lung cancer (NSCLC).

In Phase 2, DF6002 will be evaluated in combination with nivolumab in the following

indication

Cohort 2C: Advanced (unresectable or metastatic) melanoma.

Cohort 2D: Advanced (unresectable or metastatic) NSCLC.

In each study phase, patients will receive DF6002 on Day 1 every 4 weeks (Q4W). Patients will receive DF6002 until confirmed progressive disease (PD), unacceptable toxicity (ie, dose-limiting toxicity [DLT]), or any reason for withdrawal from the study or Investigational Medicinal Product (IMP) occurs.

Details
Condition Malignant neoplasm of prostate, Pulmonary Disease, Adenocarcinoma, Ovarian disorder, Endometrial Carcinoma, Malignant neoplasm of kidney, Uterine Cancer, Prostatic disorder, Breast Cancer, Ovarian Cancer, Esophageal Diseases, Esophageal Cancer, melanoma, Transitional cell carcinoma, Renal Cell Carcinoma, Lung Neoplasm, skin cancer, Gastropathy, Gastric Cancer, Bronchial Neoplasm, head and neck cancer, Stomach Discomfort, Metastatic Melanoma, Prostate Disorders, Prostate Cancer, Early, Recurrent, Solid Tumors, Ovarian Function, Solid Tumor, Esophageal Carcinoma, Squamous Cell Carcinoma of the Head and Neck, Triple Negative Breast Cancer, Solid Neoplasm, Head and Neck Squamous Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck, Gastric Carcinoma, Recurrent Ovarian Cancer, Solid Tumour, Kidney Cancer, Lung Cancer, Endometrial Cancer, Prostate Cancer, Esophageal Disorders, Malignant Melanoma, Malignant Adenoma, Lung Disease, Stomach Cancer, Renal Cell Cancer, Renal Cancer, Urothelial Carcinoma, clear cell renal cell carcinoma, prostate carcinoma, ovarian carcinomas, cancer, ovarian, cancer ovarian, cancer of the ovary, gastric cancers, esophagus cancer, oesophageal cancer, ovarian tumors, prostate cancers, cancer of the esophagus, oesophageal carcinoma, carcinoma lung, lung carcinoma
Treatment Pembrolizumab, Nivolumab, DF6002
Clinical Study IdentifierNCT04423029
SponsorDragonfly Therapeutics
Last Modified on13 June 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or female patients aged 18 years
Histologically or cytologically proven locally advanced or metastatic solid tumors, for which no standard therapy exists or standard therapy has failed among the following tumor types: melanoma, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell, urothelial, gastric, esophageal, cervical, hepatocellular, merkel cell, cutaneous squamous cell carcinoma, renal cell, endometrial, triple-negative breast, ovarian, and prostate
ECOG performance status of 0 or 1
Clinical or radiological evidence of disease
Adequate hematological, hepatic and renal function
Resolution of toxic effect(s) of prior anti-cancer therapy to Grade 1 (Patients with Grade 2 neuropathy, Grade 2 endocrinopathy or Grade 2 alopecia are exceptions)
Effective contraception for women of child-bearing potential as defined by World Health Organization guidelines for 1 "highly effective" method or 2 "effective" methods
Additional Phase 1 Monotherapy and Phase 1b Combination With Nivolumab
Expansion Inclusion
Criteria
Has one of the following tumor types: melanoma, non-small cell lung cancer, or triple negative breast cancer
Expansion Inclusion Criteria specific to Melanoma
Male or female patients aged 18 years
Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified in the American Joint Committee on Cancer staging system
Participants with ocular or uveal melanoma are ineligible
ECOG performance status of 0 or 1
PD-L1 status must be documented if available
Clinical or radiological evidence of measurable disease
BRAF (V600) mutation status must be known. Both BRAF-mutated and wild type participants are permitted in this cohort
Adequate hematological, hepatic and renal function
BRAF-mutated participants must have been treated with approved targeted therapies
Agrees to undergo a pre-treatment biopsy and another biopsy while on treatment
Must have documented progressive or recurrent disease on or after discontinuation of anti-PD-(L)1 therapy (administered as monotherapy or as part of a combination) as per RECIST 1.1 criteria
Additional Inclusion Criteria for Phase 2 (Advanced Melanoma Patients)
Participants who received anti-PD-(L)1 in the adjuvant setting must have documented progressive or recurrent disease on or within 6 months of discontinuation of anti-PD-(L)1 therapy (administered as monotherapy or as part of a combination) as per RECIST 1.1 criteria
Expansion Inclusion Criteria specific to NSCLC
Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or recurrent disease
Disease progression was confirmed at least 4 weeks after the initial diagnosis of disease progression while receiving an anti PD-1 antibody
Participants must have recurrent or progressive disease during or after platinum doublet-based chemotherapy or at least two prior lines of systemic therapy for advanced or metastatic disease OR Must have recurrent or progressive disease within 6 months after completing platinum-based chemotherapy for local disease
Received a BRAF inhibitor if the tumor carries a BRAF activating mutation and progressed after the last line of treatment
Participants must have received and progressed on or after anti-PD-(L)1 therapy, if available
Status for actionable mutations (e.g., EGFR, ALK, ROS1, RET, etc.) must be known (when testing is available as per country/region standard of care practices); participants with actionable mutations must have received and progressed on, have been intolerant to, or not be a candidate for, standard tyrosine kinase inhibitors (as available per country/region standard of care practices)
Expansion Inclusion Criteria specific to TNBC
Histologically confirmed unresectable, locally advanced or metastatic triple negative breast cancer.PD-L1 status, HER2-negative, estrogen receptor-negative, and progesterone receptor-negative status must be evaluated by local institutions before enrolment per guidelines of the American Society of Clinical Oncology and the College of American Pathologists
Patients must not have received an anti PD-1/PD-L1 for the treatment of the metastatic disease, but the administration of an anti PD-1/PD-L1 in the adjuvant setting is acceptable
Patients must have received one line of chemotherapy for the treatment of their metastatic disease, and experience progression during or after that line of chemotherapy
Patients must have not received more than one line of chemotherapy for the treatment of their unresectable, recurrent or metastatic disease
Inclusion Criteria for Phase 2 (General)
Exclusion Criteria for All Patients (All Phases)
Prior treatment with rhIL2 or any recombinant long acting drug containing an IL2 moiety
Previous malignant disease other than the current target malignancy within the last 3 years, with the exception of basal or squamous cell carcinoma of the skin, localized prostate cancer or cervical carcinoma in situ
Resolution of toxic effect(s) of prior anti-cancer therapy to Grade 1. (Patients with Grade 2 neuropathy, Grade 2 endocrinopathy or Grade 2 alopecia are exceptions.)
Participants must have received and progressed on or after anti-PD-(L)1 therapy
Rapidly progressive disease
Any Grade 2 and higher neurological or pulmonary toxicity during a treatment with an anti-PD-1 or PD-L1 agent administered as a monotherapy
Effective contraception for women of child-bearing potential as defined by World Health Organization guidelines for 1 "highly effective" method or 2 "effective" methods
Receipt of any organ transplantation, autologous or allogeneic stem-cell transplantation
Participants who received anti-PD-(L)1 in the advanced/metastatic setting, must have documented progressive or recurrent disease on or within 3 months of discontinuation of anti-PD-(L)1 therapy
Significant acute or chronic infections, or active or latent hepatitis B or active hepatitis C
Participants who received anti-PD-(L)1 in the adjuvant setting must have documented progressive or recurrent disease on or within 6 months of discontinuation of anti-PD-(L)1 therapy
BRAF mutation status must be known and treated with approved targeted therapies
Known severe hypersensitivity reactions to monoclonal antibodies and any history of anaphylaxis, or uncontrolled asthma
Serious cardiac illness or medical conditions
Participants with ocular or uveal melanoma are ineligible
Confirmation of radiographic progression on prior anti-PD-(L)1 therapy is required with a scan confirming progression at least 4 weeks after the initial progression
Additional Inclusion Criteria for Phase 2 (Non-small Cell Lung Cancer)
Participants must have recurrent or progressive disease during or after platinum doublet-based chemotherapy or at least two prior lines of systemic therapy for advanced or metastatic disease OR must have recurrent or progressive disease within 6 months after completing platinum-based chemotherapy for local disease
Status for actionable mutations must be known; participants with actionable mutations must have received and progressed on, have been intolerant to, or not be a candidate for, standard tyrosine kinase inhibitors
Concurrent anticancer treatment (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
Active or history of central nervous system (CNS) metastases unless all of the following criteria are met
CNS lesions are asymptomatic and previously treated
Patient does not require ongoing steroid treatment daily for replacement for adrenal insufficiency
Imaging demonstrates stability of disease 28 days from last treatment for CNS metastases
Preexisting autoimmune disease needing treatment with systemic immunosuppressive agents for more than 28 days within the last 3 years, clinically relevant immunodeficiencies, or fever within 7 days of Day 1
History of life-threatening toxicity related to prior immune therapy except those that are unlikely to re-occur with standard countermeasures
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