Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial

David S. Hong, Brian A. Van Tine, Swethajit Biswas, Cheryl McAlpine, Melissa L. Johnson, Anthony J. Olszanski, Jeffrey M. Clarke, Dejka Araujo, George R. Blumenschein, Partow Kebriaei, Quan Lin, Alex J. Tipping, Joseph P. Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam FernandesJean Marc Navenot, Frederic D. Bushman, John K. Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G. Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand’Maison, Philip McCarthy, Paula M. Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A. Liebner, Kunle Odunsi, Marcus O. Butler

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer (NCT03132922). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit–risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies.

Original languageEnglish
Pages (from-to)104-114
Number of pages11
JournalNature medicine
Volume29
Issue number1
DOIs
StatePublished - Jan 2023

Fingerprint

Dive into the research topics of 'Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial'. Together they form a unique fingerprint.

Cite this