Registrational Trial of AFM13 Will Continue Following Success of Preplanned Interim Analysis

March 11, 2021
Audrey Sternberg

A phase 2 trial of single-agent AFM13, a bispecific tetravalent innate cell engager that binds to CD30, will continue following positive results of a preplanned interim futility analysis.

The phase 2 registrational REDIRECT trial (NCT04101331) studying the efficacy and safety of single-agent AFM13 in patients with relapsed/refractory CD30-positive peripheral T-cell lymphoma (PTCL) or Transformed Mycosis Fungoides has superseded the threshold for continuation at a preplanned interim futility analysis, according to Affimed N.V., the agent’s developer.1

Based on these results that were triggered after enrollment of 20 participants, the trial will continue to enroll with few changes to the study protocol.

“We are encouraged by the observed activity of AFM13 in this heavily pretreated patient population, where more than half of the patients had 3 or more lines of previous therapy. These data reinforce our strategy to broadly develop AFM13 across CD30-positive lymphomas both as monotherapy and in combination with other therapies,” said Dr. Andreas Harstrick, MD, Affimed’s chief medical officer, said in a press release. “Having successfully met the criteria for continuation, the trial will move forward by merging the CD30 high- and low-expressing PTCL cohorts for evaluation of the safety and efficacy of AFM13.”

Originally, patients in cohort A were those with CD30 expression of 10% or greater whereas those in cohort B had between 1% and 10% expression rates. The futility boundary, which was derived from response rates in prior studies of other therapies for relapsed/refractory PTCL, was achieved in cohort A and was sufficiently comparable in cohort B. These findings taken together allowed for the merging of both cohorts into a single cohort with CD30 expression of 1% or more. Antitumor activity was noted in both cohorts, with complete and partial responses seen across the study population.

The safety profile was consistent with prior data of AFM13 in phase 1 trials, with infusion-related reaction being the most concerning adverse event. With the inclusion of mandatory premedication, infusion-related reactions were significantly reduced and led to fewer dose reductions.

“We are excited by this progress and by AFM13’s potential as monotherapy for patients with PTCL,” Won Seog Kim, MD, PhD, Principal Investigator of REDIRECT and Professor of Hematology and Oncology at the Samsung Medical Center, Sungkyunkwan University, Seoul, Korea, said in a press release. “PTCL is an aggressive and challenging cancer to treat in patients who relapse or do not respond favorably to current therapies, which often have high toxicity profiles, and new therapeutic approaches are needed.”

AFM13 is a bispecific tetravalent innate cell engager, or ICE, that targets CD30 on tumor cells and natural killer (NK) cells and macrophages.

In April 2020, AFM13 was granted orphan drug designation for the treatment of patients with T-cell lymphoma, including PTCL.2

In a presentation at the 2020 American Society of Hematology Annual Meeting, AFM13 monotherapy demonstrated a response rate of 42% in 14 patients with CD30-positive lymphomas treated on a phase 1b/2 trial (NCT03192202). Circulating NK cells decreased during therapy, as made evident by flow cytometry monitoring. Tumor biopsies from patients who responded to therapy showed increased pre-therapy CD56-positive NK cell infiltration versus those who did not respond, suggesting that AFM13 may enlist and promote infiltration of NK cells.3

References:

1. Affimed Announces Continuation of REDIRECT, a Registration-directed Study of AFM13 in PTCL, after Positive Preplanned Interim Futility Analysis. News release. Affimed N.V. March 8, 2021. Accessed March 10, 2021. https://bit.ly/38v5lcR

2. Affimed announces FDA granted orphan drug designation for lead innate cell engager AFM13 for the treatment of T-cell lymphoma. News release. Affimed N.V. April 1, 2020. Accessed March 10, 2021. https://bit.ly/3rAgXTl

3. Affimed announces updated AFM13 clinical data presentation at the American Society of Hematology Annual Meeting, demonstrating good tolerability and a high objective response rate in patients with recurrent/refractory CD30-positive lymphoma with cutaneous presentation. News release. Affimed N.V. December 7, 2020. Accessed March 10, 2021. https://bit.ly/30y9J6y