DF1001 Gets Orphan Drug Designation From FDA for Esophageal Cancer

FDA

The FDA has granted an orphan drug designation to the HER2-targeted natural killer (NK) cell engager therapy, DF1001, as a potential therapeutic option for patients with esophageal cancer, according to an announcement from Dragonfly Therapeutics, Inc., the drug developer.¹

DF1001 was designed to target NK cells and T-cell activation signals to specific receptors on cancer cells. The agent was developed using the TriNKET platform, which enhances the benefits derived with immunotherapy by leveraging NK cells.² NK cells eliminate cancer cells directly and activate T cells and B cells. This helps B cells to produce antitumor antibodies and to activate more T cells that allow for the elimination of cancer cells.

“Overall, NK cells amplify the effectiveness of T cells, acting as a sentinel that calls other immune system cells to attack the cancer, as well as broadening the therapeutic window (or safety profile) by using their special characteristics of distinguishing cancer, to more specifically target tumor cells,” according to Dragonfly Therapeutics, Inc.

DF1001 is under investigation in an ongoing first-in-human, phase 1/2 study (NCT04142711) that is examining the agent in patients with solid tumors.³ To be eligible for participation, patients need to be at least 18 years of age, have histologically or cytologically confirmed locally advanced or metastatic solid tumors, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, a baseline left ventricular ejection fraction of 55% or greater, and acceptable hematologic, hepatic, and renal function.

The trial is estimated to enroll approximately 220 patients. The first phase of the research will be the dose-escalation phase in which patients with various types of HER2-expressing solid tumors will be enrolled. Two cohorts will be opened for enrollment to examine DF1001 in combination with either nivolumab (Opdivo) or nab-paclitaxel (Abraxane).

The second phase of the trial will be the dose-expansion phase in which the agent will be evaluated at the best dose selected in the prior phase. Several cohorts will open and will enroll patients with either select solid tumors or solid tumors that expressed high levels of HER2.

The primary outcome measures of the trial include assessment of dose-limiting toxicities and overall response rates. Key secondary outcomes include serum concentrations of DF1001, evaluation of DF1001 immunogenicity, best overall response, duration of response, progression-free survival, overall survival, adverse effects (AEs) with DF1001 plus nivolumab, and AEs with DF1001 plus nab-paclitaxel.

The study is currently recruiting in California, Kansas, Maryland, Michigan, New York, Ohio, Pennsylvania, Rhode Island, Tennessee, and Texas.

References

1. Dragonfly Therapeutics announces DF1001 granted orphan drug designation in the US for esophageal cancer. News release. Dragonfly Therapeutics, Inc. November 9, 2021. Accessed November 9, 2021. https://prn.to/305edV6
2. Our platform: TriNKET. Dragonfly Therapeutics, Inc. website. Accessed November 9, 2021. https://bit.ly/3C319g6
3. Study of DF1001 in patients with advanced solid tumors. ClinicalTrials.gov. Updated August 3, 2021. Accessed November 9, 2021. https://clinicaltrials.gov/ct2/show/NCT04143711