ASCO24: Regeneron’s Bispecific Antibody Disappoints in Early Study

Regeneron Pharmaceuticals recently disclosed early data from its ongoing Phase I/II trial of the investigational bispecific antibody REGN7075, targeting patients with advanced solid tumors. The preliminary results, as of the October 13, 2023, data cut-off, have shown modest treatment responses. Out of 94 patients, only one achieved a complete response, and two had partial responses. An additional patient with liver metastasis showed partial response post cut-off. Nine patients maintained stable disease states.

These findings translate to an overall response rate of 20% and a disease control rate of 80%. Despite the modest efficacy, Israel Lowy, Regeneron's senior vice president of translational and clinical oncology, expressed optimism about REGN7075's potential in treating solid tumors. He highlighted that these early results contribute to the expanding evidence supporting novel costimulatory bispecifics currently in clinical trials for various solid and blood cancers.

REGN7075 is a pioneering costimulatory bispecific antibody designed to link CD28-positive T cells with tumor cells that express the EGFR protein. This mechanism aims to restore the immune sensitivity of tumor cells and activate T-cell anti-cancer functions. The ongoing Phase I/II study is the first human trial for REGN7075, administered in combination with the PD-1 blocker Libtayo (cemiplimab-rwlc), targeting patients with metastatic and locally advanced solid tumors who have no remaining standard treatment options.

The trial comprises two sections: a Phase I dose-escalation part, which includes an initial period with REGN7075 monotherapy, and a Phase II dose-expansion part. The primary focus of these early stages is to evaluate the safety and tolerability of the REGN7075 regimen, which Regeneron has so far deemed "acceptable."

Nearly all participants experienced treatment-emergent adverse events (TEAE), with 35% encountering grade 3 or 4 TEAEs. While 90% of patients had side effects related to the study drug, only 7% were of grade 3 or 4 severity. Additionally, 5% of participants withdrew from the study due to side effects. Importantly, no treatment-related deaths have been reported.

This latest update continues a challenging period for Regeneron's oncology endeavors. In March 2024, the company failed to gain FDA approval for another bispecific antibody, odronextamab, intended for relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma, despite promising Phase II data from December 2023. Furthermore, another bispecific, linvoseltamab, yielded mixed results in December 2023. Although it showed a 71% objective response rate in treating relapsed or refractory multiple myeloma, it also presented high adverse event rates, with 85% of patients experiencing side effects of at least grade 3 severity.