A phase II study of acimtamig (AFM13) in patients with CD30-positive, relapsed, or refractory peripheral T-cell lymphomas Journal Article
| Authors: | Kim, W. S.; Shortt, J.; Zinzani, P. L.; Mikhailova, N.; Radeski, D.; Ribrag, V.; Domenech, E. D.; Sawas, A.; Alexis, K.; Emig, M.; Elbadri, R.; Hajela, P.; Ravenstijn, P.; Pinto, S.; Garcia, L.; Overesch, A.; Pietzko, K.; Horwitz, S. |
| Article Title: | A phase II study of acimtamig (AFM13) in patients with CD30-positive, relapsed, or refractory peripheral T-cell lymphomas |
| Abstract: | Purpose: Patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) generally have poor prognoses and limited treatment options. This study evaluated the efficacy of a novel CD30/CD16A bispecific innate cell engager, acimtamig (AFM13), in patients with R/R PTCL. Patients and Methods: Patients included those with CD30 expression in ≥1% of tumor cells and who were R/R following ≥1 prior line of systemic therapy. Acimtamig (200 mg) was administered once weekly in 8-week cycles. The primary endpoint was the overall response rate by fluorodeoxyglucose-PET per independent review committee; secondary and exploratory endpoints included duration of response, safety, progression-free survival, and overall survival. Results: The overall response rate in 108 patients was 32.4% [95% confidence interval (CI), 23.7, 42.1] with a complete response rate of 10.2% (95% CI, 5.2, 17.5); the median duration of response was 2.3 months (95% CI, 1.9, 6.5). Patients with R/R angioimmunoblastic T-cell lymphoma exhibited the greatest number of responses [53.3% (95% CI, 34.3, 71.7)]. Responses were independent of CD30 expression level, prior brentuximab vedotin treatment, or steroid premedication. Acimtamig exhibited a tolerable safety profile; the most common treatment-related adverse events were infusion-related reactions in 27 patients (25.0%) and neutropenia in 11 patients (10.2%). No cases of cytokine release syndrome or acimtamig-related deaths were reported. Despite exhibiting promising clinical activity and tolerable safety in a heavily pretreated PTCL population, the study did not meet the criteria for the primary endpoint. Conclusions: The promising clinical efficacy observed warrants further investigation, and development of acimtamig for patients with R/R CD30+ lymphomas continues in combination with allogeneic NK cells. ©2024 The Authors. |
| Keywords: | adult; controlled study; treatment response; aged; major clinical study; overall survival; neutropenia; area under the curve; drug efficacy; drug safety; drug withdrawal; side effect; systemic therapy; treatment duration; flow cytometry; positron emission tomography; cancer immunotherapy; progression free survival; multiple cycle treatment; phase 2 clinical trial; relapse; dexamethasone; antineoplastic activity; risk assessment; chill; fever; pneumonia; lung embolism; peripheral t cell lymphoma; regulatory t lymphocyte; blood sampling; paracetamol; multicenter study; immunogenicity; tumor cell; natural killer cell; immunophenotyping; drug therapy; romidepsin; adverse drug reaction; pralatrexate; lymphocyte count; peripheral blood mononuclear cell; belinostat; diphenhydramine; premedication; tumor microenvironment; cytokine release syndrome; overall response rate; famotidine; angioimmunoblastic t cell lymphoma; brentuximab vedotin; infusion related reaction; human; male; female; article; tumor necrosis factor receptor superfamily member 8; acimtamig; afm13 |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 1 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-01-01 |
| Start Page: | 65 |
| End Page: | 73 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-1913 |
| PUBMED: | 39531538 |
| PROVIDER: | scopus |
| PMCID: | PMC11701429 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
