Next steps may include assessing AFM13 in combination with natural killer cells.
AFM13, a tetravalent, bispecific innate cell engager CD30+ therapy was well tolerated and showed clinical activity in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) subtypes, according to recent data from the phase 2, multi-cohort, open-label, REDIRECT trial (NCT04101331).
Data from the trial were presented at the American Associated for Cancer Research (AACR) Annual Meeting 2023, held April 14-19 in Orlando, Florida, by Won Seog Kim, MD, PhD, professor, hematology/oncology, Sungkyunkwan university, lymphoma specialist, SamsungMedicalCenter, Seoul, Korea.
“PTCL is a heterogeneous group of aggressive lymphomas with generally poor outcomes... Even with frontline treatment, outcomes are not so satisfactory and with refractory cases we don't have any established standard of care... many patients with PTCL have tumor cells that express CD30... which we know can be a good target,” Kim said during his presentation.
REDIRECT is primarily assessing the efficacy of AFM13 in patients with R/R PTCL by overall response rate (ORR). Secondary endpoints include safety, duration of response (DOR), complete response rate (CRR), immunogenicity, pharmacokinetics, and quality of life. Patients were divided into 2 cohorts with similar base characteristics of at least 10% CD30 expression (n = 30) and between 1 and 10% CD30 expression (n = 21). PTCL subtypes included PTCL not-otherwise-specified (PTCL-NOS; n, 41; 38%), angioimmunoblastic T cell lymphoma (AITL; n, 30; 27.8%), anaplastic large cell lymphoma (ALCL; n, 26; 24.1%), or other (n, 11; 11.1%). Participants had a mean age of 63 years (range, 21-93), 61% were male and there was a mean 2.7 prior lines of therapy. Around half (n, 50; 46.3%) of participants had prior brentuximab vedotin treatment and 38.9% (n = 42) had prior auto transplant.
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“From the 2 prior trials with FM13 as a monotherapy in R/R Hodgkin lymphoma (HL) and cutaneous presenting t-cell malignancies, we already confirmed the therapy’s efficacy with no safety issues, and interestingly, no cytokine release syndrome. Based on these trials, the RP2D of 200 mg AFM13 was established,” Kim added.
A total of 108 patients received 200 mg intravenous AFM13 treatment once a week, which continued until disease progression, intolerable toxicity, withdrawal of consent, of termination at the investigator’s discretion. Patients received a median of 9 infusions (range, 1-116; mean, 16). Most patients (85%) received the full 200 mg dose at all infusions and 11% of patients had at least 1 dose reduction.
No new or unexpected safety findings were observed, with treatment-related adverse events (AEs) occurring in 73.1% (n = 79) of participants. Nine patients experienced 14 serious related AEs and 2 related AEs led to study discontinuation. The most common treatment-emergent AEs were infusion-related reactions (31.5%, 5.7% grade 3), the most common of which was neutropenia (9.3% grade 3).
Investigators found that ORR was 32.4% and CRR was 10.2%; by subgroup ORR was 22.0% in PTCL-NOS, 53.3% in AITL, 23.1% in ALCL, and 36.4% in the other subgroup. Median DOR was 2.3 months (95% CI, 1.9-6.5), median duration of CR was 3.6 months (95% CI, 1.9-NE) progression free survival was 3.5 months (95% CI, 1.9-3.6), and overall survival was 13.8 months (95% CI, 5.0-NE). Overall, over 60% of patients experienced tumor shrinkage and clinical benefit. There were no significant differences in responses between cohorts of CD30 expression.
“Right now, the combination [of AFM13] with allogeneic natural killer cells is being assessed in a trial in R/R HL with encouraging efficacy. Maybe this is the next step with AFM13 in PTCL strategy,” Kim concluded.
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