A phase 1/2 study of REGN7075 (EGFRxCD28 costimulatory bispecific antibody) in combination with cemiplimab (anti–PD-1) in patients with advanced solid tumors, including colorectal cancer: Trial in progress update.
Authors: Neil Howard Segal, Eugenia Girda, Davendra Sohal, Nehal J. Lakhani, Anthony J. Olszanski, Lawrence Fong, Hyunsil Han, Kerry A. Casey, Siyu Li, Samit Ganguly, Frank A. Seebach, Melissa Divya Mathias, Meredith Pelster
Journal: Journal of Clinical Oncology (2024)

TPS239 Background: REGN7075 is a human costimulatory bispecific antibody designed to bridge epidermal growth factor receptor (EGFR)-expressing tumor cells with CD28 on the surface of T cells to drive co-stimulation and recognition of endogenous tumor antigens. EGFR-targeted therapies are approved in head and neck squamous cell carcinoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). Methods: This is an open-label, Phase 1/2, first-in-human, international study evaluating the safety, tolerability, PK, and anti-tumor activity of REGN7075 ± cemiplimab (anti–PD-1) in patients (pts) with solid tumors (NCT04626635). Here we focus on the cohorts of pts with microsatellite-stable-CRC (MSS-CRC). The study includes a dose-escalation phase (Part 1) and a dose-expansion phase (Part 2). In Part 1, pts will receive a 3-week REGN7075 monotherapy once-weekly (QW) lead-in prior to combination therapy with REGN7075 QW or every 3 weeks (Q3W) + cemiplimab Q3W. Concurrent Q3W dosing with cemiplimab may be conducted for dose levels for which the lead-in is tolerable; to date, this has been up to a dose of 900 mg. After a tolerable dose and schedule of interest is identified in Part 1, Part 2 may consist of eight tumor-specific expansion cohorts, including two cohorts of pts with metastatic MSS-CRC or locally advanced CRC (not candidates for curative surgery/radiation), who have received at least one prior line of therapy (anti–EGFR for RAS wild type disease, anti–VEGF, or documented reason why not appropriate). One cohort will include pts with MSS-CRC with active liver and/or peritoneal metastases, and the other will include pts with MSS-CRC with only lung and/or lymph node metastases. Overall, key inclusion criteria are: evidence of a protocol-defined advanced solid tumor, an ECOG performance status of 0 or 1, and no previous anti–PD-1/anti–PD-(L)1 therapy (Part 2 only). The analyses of Part 1 will be descriptive and exploratory in nature. Primary endpoints are safety and tolerability of REGN7075 ± cemiplimab (Part 1), and objective response rate per RECIST 1.1 (Part 2). Secondary endpoints include: REGN7075 concentrations in serum and overall survival (both parts); incidence and severity of treatment-emergent adverse events (AEs), AEs of special interest, serious AEs, and Grade ≥3 laboratory abnormalities; incidence and titer of ADA to REGN7075 + cemiplimab over time; pt-reported quality of life, symptoms, functioning, and general health status (Part 2 only). The study is expected to enroll ~769 pts: ~221 pts in Part 1 and ~548 pts in Part 2, including 74 pts in Cohort E and 73 pts in Cohort F. As of September 5, 2023, 93 pts were enrolled in Part 1. This study is ongoing and currently open to enrollment. Clinical trial information: NCT04626635 .