ASCO: Regeneron sees only one complete response in solid tumor trial despite high hopes

Regeneron Pharmaceuticals is actively recruiting patients for its open-label phase 1/2 trial targeting metastatic and locally advanced solid tumors. Despite anticipation from analysts for significant response rates, recent data reveals only one complete response among 94 patients treated with Regeneron's costimulatory bispecific antibody, REGN7075.

The investigational therapy, which combines REGN7075 with Libtayo, showed limited efficacy in the initial data set presented in November 2022. Among 18 patients treated with up to 30 mg of REGN7075, only one achieved a partial response. Updated results from May 23 indicate that out of 94 evaluable patients, there was one complete response and two partial responses, amounting to a 6% overall response rate (ORR). The disease control rate (DCR) stood at 29%.

A significant portion of the patients (65%, or 61 individuals) had microsatellite stable colorectal cancer (MSS CRC), a variant known for its resistance to immunotherapy. This subset's data will be presented at the upcoming American Society of Clinical Oncology (ASCO) annual meeting. Out of 51 MSS CRC patients treated at the active dosing level, three responded, leading to an ORR of 20% within the subgroup without liver metastases.

Dr. Israel Lowy, Senior Vice President of Translational and Clinical Oncology at Regeneron, highlighted the difficulty of treating patients with liver metastases due to the immune-suppressive environment. He noted that one patient with liver metastasis later responded to the treatment, although this data was not included in the current cutoff.

Despite the modest response rates, Regeneron remains optimistic about the combination therapy's potential for patients unresponsive to standard treatments. Analysts from Leerink Partners had hoped for more robust responses, which could enhance confidence in Regeneron's costimulatory bispecifics platform. This platform aims to link T-cells to cancer cells, modifying CD28 signaling to enhance anti-tumor activity in combination with Libtayo or CD3 bispecifics.

Safety data from the trial was also shared, showing that treatment-related adverse events (TRAEs) led to discontinuation in 5% of cases and grade 2 infusion-related reactions caused three more patients to stop treatment. Among 84 patients assessed, 98% experienced treatment-emergent adverse events, with 90% facing TRAEs. Severe TRAEs (grades 3 or 4) occurred in 7% of patients, while the majority were low-grade events, primarily manageable infusion-related reactions.

There were no dose-limiting toxicities or treatment-related deaths, although the safety data had a different cutoff than the efficacy results. In a separate trial involving REGN5678, a bispecific antibody for prostate cancer, two deaths occurred, prompting Regeneron to amend the study protocol to lower dose levels.

Regeneron is investigating multiple costimulatory agents, including REGN5668 for ovarian cancer. Dr. Lowy emphasized the uniqueness of each agent and the exploration of optimal combinations, including potential benefits for CAR-T programs acquired from 2seventy bio.

The company's new data is encouraging for a patient population with limited options, particularly MSS CRC patients. Dr. Neil Segal of Memorial Sloan Kettering Cancer Center noted the significance of the trial's clinical activity in MSS CRC, traditionally unresponsive to immunotherapy.

The ongoing trial aims to enroll 769 participants, with the phase 1 dose-escalation portion and phase 2 dose-expansion period progressing. The primary completion date is set for August 2026. Regeneron is also evaluating REGN7075 in combination with CD3 bispecifics and other chemotherapies, hoping to see improved outcomes.

Regeneron remains committed to exploring these innovative therapies, aiming to provide new options for patients with challenging cancer types.

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