On May 23, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported positive new results from an ongoing Phase 1/2 trial evaluating its first-in-class costimulatory bispecific antibody, REGN7075 (EGFRxCD28), in combination with Libtayo (cemiplimab) in patients with advanced solid tumors (Press release, Regeneron, MAY 23, 2024, View Source [SID1234643614]). Data from the dose-escalation portion of the trial showed the investigational combination led to anti-tumor responses in patients with microsatellite stable colorectal cancer (MSS CRC). REGN7075 is one of the first immunotherapies to demonstrate clinical activity in MSS CRC, including in a patient with liver metastases. The results will be shared during an oral session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting in Chicago.
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"Microsatellite stable colorectal cancer has historically been unresponsive to immunotherapy," said Neil H. Segal, M.D., Ph.D., Medical Oncologist and Research Director in the Division of Gastrointestinal Oncology at Memorial Sloan Kettering Cancer Center, and a trial investigator. "The early results for this novel investigational EGFRxCD28 costimulatory bispecific in combination with Libtayo are encouraging, showing anti-tumor responses in a highly difficult-to-treat cancer. This combination is one of the first immunotherapy regimens to show clinical activity in microsatellite stable colorectal cancer, and we are excited to advance this trial in additional tumor types."
In the dose-escalation portion of the trial, patients with metastatic and locally advanced solid tumors – who had exhausted standard treatment options, and most of whom also had liver metastases – received combination therapy with REGN7075 and Libtayo, following a REGN7075 monotherapy lead-in dose. Among 94 patients treated as of data cutoff, 65% (n=61) had MSS CRC, of which 51 MSS CRC patients were treated at an active dose level. Efficacy results among these 51 patients were as follows:
6% (n=3) overall response rate (ORR) and 29% (n=15) disease control rate (DCR). This included one complete response (CR), two partial responses (PR), and 12 patients with stable disease. At data cutoff, all responders were without liver metastases.
Among the subset of 15 patients without liver metastases, there was a 20% ORR (n=3) and 80% DCR (n=12).
Among the subset of 36 patients with liver metastases, three patients had stable disease as of data cutoff, and one patient achieved a PR following data cutoff.
Safety was assessed in 84 patients across multiple solid tumor types at a variety of doses of REGN7075. REGN7075 and Libtayo showed an acceptable safety profile, and the maximum tolerated dose was not reached. Treatment-emergent adverse events (TEAEs) of any grade occurred in 98% of patients; Grade 3 and 4 TEAEs occurred in 35% of patients. Treatment-related adverse events (TRAEs) occurred in 90% of patients, with 7% of cases reported as grade 3 or 4. The majority of TRAEs were Grade 1 to 2 (83%), with the most common being infusion-related reactions (58%) that were manageable with premedication and dosing adjustments. TRAEs led to discontinuation in 5% of patients, and three patients discontinued treatment due to Grade 2 infusion-related reactions. As of data cutoff, there have been no dose-limiting toxicities, no reports of cytokine release syndrome, and no treatment-related deaths.
"Regeneron is focused on developing a unique investigational portfolio of oncology medicines including checkpoint inhibitors, CD3 bispecifics and CD28 costimulatory bispecifics. Over the past several years, we have made progress in our programs across checkpoint inhibitors and the CD3 class and are now showing promising activity with two costimulatory bispecific antibodies," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Oncology at Regeneron. "Our costimulatory bispecifics were designed with the goal of turning cancer cells into antigen presenting cells, thereby converting historically immunotherapy unresponsive tumors from ‘cold’ to ‘hot’. These early data speak to the potential of REGN7075 in combination with Libtayo and add to a growing body of evidence supporting novel costimulatory bispecifics that are in clinical trials for a range of solid tumors and blood cancers."
The combination of REGN7075 and Libtayo is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority. While the dose escalation portion of the trial across multiple solid tumor types including non-small cell lung cancer, colorectal cancer, head and neck cancer and other tumor types is ongoing, expansion cohorts in several tumor types have also been initiated.
About the Phase 1/2 Trial
The Phase 1/2, first-in-human, open-label trial investigating REGN7075 in combination with Libtayo is currently enrolling patients with metastatic and locally advanced solid tumors who have exhausted standard treatment options. The trial includes an ongoing Phase 1 dose-escalation portion and a Phase 2 dose-expansion period. In the Phase 1 dose-escalation portion, patients first receive a weekly lead-in dose of REGN7075 monotherapy for three weeks to assess its safety and efficacy alone. This is followed by treatment with combination therapy, with Libtayo dosed once every three weeks and REGN7075 dosed either every week or every three weeks. The primary endpoints are assessing safety and tolerability, while the secondary endpoints are assessing efficacy, pharmacokinetics and immunogenicity. Expansion cohorts in several tumor types have been initiated. For more information, visit the Regeneron clinical trials website, or contact via [email protected] or 844-734-6643.