Regeneron Pharmaceuticals, Inc. announced 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. 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) 2024 Annual Meeting in Chicago. 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. 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.

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.

U.S. FDA-approved Indications: Libtayo is a prescription medicine used to treat: People with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation. People with a type of skin cancer called basal cell carcinoma (BCC) when BCC cannot be removed by surgery (locally advanced BCC) or when it has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with a HHI. Adults with a type of lung cancer called non-small cell lung cancer (NSCLC).

LIBTAYO may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when lung cancer has not spread outside chest (locally advanced lung cancer) and cannot have surgery or chemotherapy with radiation, or lung cancer has spread to other areas of body (metastatic lung cancer), and tumor does not have an abnormal ?EGFR,? ?ALK,? or ?ROS1?

gene. LIBTAYO may be used alone as first treatment when lung cancer has not spread outside chest (locally advanced lung cancer) and cannot have surgery or chemotherapy with radiation, or lung cancer has spread to other areas of body (metastatic lung cancer), and tumor tests positive for high ?PD-L1,? and tumor does not have an abnormal ?EGFR,?

?ALK,? or ?ROS1? gene.

LIBTAYO is a medicine that may treat certain cancers by working with your immune system. LIBTAYO can cause immune system to attack normal organs and tissues in any area of body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death.