AFM13 Exhibits Efficacy in CD30+ Relapsed/Refractory PTCL

The investigational tetravalent bispecific antibody AFM13 displayed clinical efficacy in heavily pretreated patients with CD30-positive relapsed/refractory peripheral T-cell lymphoma (PTCL), according to findings from the phase 2 REDIRECT trial (NCT04101331).

The results, which were presented during the 2023 AACR Annual Meeting, showed that patients treated with the agent (N = 108) experienced an overall response rate (ORR) of 32.4% (95% CI, 23.7%-42.1%), including a complete response rate (CRR) of 10.2% (95% CI, 5.4%-18.1%). Responses were determined by fluorodeoxyglucose-positron emission tomography (FDG-PET) per independent review committee (IRC) assessment.

“PTCL is a heterogenous group of malignancies where the outcomes are generally very poor,” Won Seog Kim, MD, an oncologist at Samsung Medical Center and Sungkyunkwan University in Seoul, South Korea, said in a presentation of the data. “The median overall survival [OS] is 1 to 3 years [depending on] the histologic subtype, and the median 5-year OS rate is less than 25%. Many patients with PTCL [have tumor cells that] are expressing CD30 [depending on] histologic subtype. From experience with brentuximab vedotin (Adcetris), we know that CD30 can be a very charming therapeutic target.”

AFM13 is a bispecific CD30/CD16 antibody designed to redirect and enhance natural killer (NK) cell–mediated antibody-dependent cellular cytotoxicity. Study authors hypothesized that augmenting innate immunity with the agent could lead to an effective treatment approach for patients with relapsed/refractory CD30-positive PTCL.

REDIRECT was an open-label, multicenter study of patients with CD30-positive relapsed/refractory PTCL who had received at least 1 prior line of systemic therapy. A CD30 expression level of at least 1% in PTCL cells was required for inclusion. Patients with central nervous system involvement, those with non-PTCL subtypes of lymphoma, those who required systemic immunosuppressive therapy, and those who had undergone an allogeneic hematopoietic cell or solid organ transplant within the past 3 years were excluded from the trial.

Enrolled patients received AFM13 at a dose of 200 mg intravenously once per week until disease progression, unacceptable toxicity, termination per investigator’s discretion, or withdrawal. The primary end point was ORR by IRC assessed by FDG-PET. Secondary end points included safety, CRR, duration of response (DOR), and ORR by computed tomography scan and investigator assessment. OS and progression-free survival (PFS) represented exploratory end points.

The median patient age was 63 years (range, 21-93) and most patients were males (61.1%). PTCL subtypes consisted of PTCL-not otherwise specified (NOS; 38.0%), angioimmunoblastic T-cell lymphoma (AITL; 27.8%) systemic anaplastic large cell lymphoma (sALCL; 24.1%) and other (11.1%).

The mean number of prior lines of therapy was 2.7. Patients underwent 1, 2, or at least 3 prior lines of therapy at a rate of 21.3%, 32.4%, and 46.3%, respectively. Prior brentuximab vedotin and autologous transplant were reported in46.3% and 38.9% of patients, respectively.

Patients underwent a mean number of 16 infusions of AFM13, with a median of 9. The mean relative dose intensity was 91%. Most patients (85%) received 200 mg of AFM13 at all infusions and 11% experienced at least 1 dose reduction.

Notably, additional findings showed that patients with AITL experienced an ORR of 53.3% (95% CI, 34.3%-71.7%) with a CRR of 26.7% (95% CI, 12.3%-45.9%). Patients with PTCL-NOS, sALCL, and other PTCL subtypes experienced ORRs of 22% (95% CI, 10.6%-37.6%), 23.1% (95% CI, 9.0%-43.6%), and 36.4% (95% CI, 10.9%-69.2%), respectively. The CRRs for these patients were 2.4% (95% CI, 0.1%-12.9%), 3.8% (95% CI, 0.1%-19.6%), and 9.1% (95% CI, 0.2%-41.3%), respectively.

The ORR was similar across CD30 expression levels. Patients with CD30 expression of at least 1% to less than 5% had an ORR of 26.7% (95% CI, 7.8%-55.1%), and those with an expression level ranging from at least 5% to less than 10% had an ORR of 30.8% (95% CI, 9.1%-61.4%). The ORR was 35.9% (95% CI, 21.2%-52.8%) and 30.6% (95% CI, 16.4%-48.1%) among patients with a CD30 expression of at least 10% to less than 50% and those with a level at or above 50%, respectively.

The median DOR was 2.3 months (95% CI, 1.9-6.5), and the median duration of complete response was 3.6 months (95% CI, 1.9-not evaluable [NE]).

In terms of survival outcomes, the median OS was 13.8 months (95% CI, 5.0-NE). The median PFS was 3.5 months (95% CI, 1.9-3.6).

Regarding safety, treatment-emergent adverse events (TEAEs) occurred in most patients (97.2%), 73.1% of which were AFM13-related. TEAEs of grade 3 or higher occurred in 53.7% of patients, 39.8% had serious TEAEs, 12.0% had TEAEs leading to AFM13 discontinuation, and 5.6% experienced fatal TEAEs. These events were determined to be related to AFM13 in 30.6%, 8.3%, 1.9%, and 0% of patients, respectively.

Common grade 1 or 2 TEAEs included infusion-related reaction (19.4%), pyrexia (7.4%), nausea (6.5%), chills (5.6%), and thrombocytopenia (4.6%). TEAEs of grade 3 or 4 included neutropenia (7.4%), infusion-related reaction (5.6%), anemia (3.7%), and thrombocytopenia (1.9%). Grade 5 AFM13-related TEAEs were not observed.

“[A trial investigating] the combination of AFM13 with AB-101 allogeneic NK cells is underway in [patients with] relapsed/refractory Hodgkin’s lymphoma, with an encouraging ORR of over 90% [among patients treated at the recommended phase 2 dose]. This may be the next step with AFM13 in PTCL [treatment] strategies,” Kim concluded.

Editor's Note: Dr Kim reports grant/research support from Sanofi, Beigene, Boryong, Roche, Kyowa-Kirin, and Donga.

Reference

Kim WS, Shortt J, Zinzani PL, et al. REDIRECT: a phase 2 study of AFM13 in patients with CD30-positive relapsed or refractory (R/R) peripheral T cell lymphoma (PTCL). Presented at: 2023 AACR Annual Meeting; April 14-19, 2023; Orlando, FL. Abstract CT024.