invoX Pharma Shares Promising Phase 1 Data on FS222 for Advanced Solid Tumours at 2024 ASCO Meeting

invoX Pharma Limited, a globally focused biopharmaceutical company dedicated to innovative research, recently shared promising data from its phase 1 clinical trial of FS222, an investigational bispecific antibody targeting CD137/PD-L1. The announcement was made at the 2024 American Society of Clinical Oncology Annual Meeting in Chicago.

FS222 is a pioneering tetravalent bispecific antibody developed using invoX's proprietary Fcab® platform. It leverages PD-L1 dependent CD137 agonism for its mechanism of action. The ongoing first-in-human (FIH) dose-escalation study (NCT04740424) involves 100 participants with advanced solid tumors. The primary goal of the trial is to assess safety and determine the maximum tolerated dose, while secondary objectives include evaluating anti-tumor efficacy, pharmacokinetics, and pharmacodynamics.

When administered as a monotherapy every four weeks, FS222 induced T cell proliferation and increased intratumoral CD8+ T cell infiltration at various dose levels. Treatment-related adverse events (TRAEs) were generally dose-dependent, aligning with the dual mechanism of CD137 activation and PD-L1 inhibition. TRAEs were mostly manageable and reversible, with Grade 3 or higher TRAEs observed in 36 out of 100 patients. Common high-grade adverse events included elevations in liver enzymes (aspartate aminotransferase and alanine aminotransferase), thrombocytopenia, neutropenia, and febrile neutropenia.

FS222 showed notable anti-tumor activity across multiple cancer types. Responses, as defined by RECIST1.1 criteria, were recorded in patients with cutaneous melanoma (9 cases), ovarian cancer (2 cases), non-small cell lung cancer (NSCLC) (2 cases), and one case each of mucosal melanoma, triple-negative breast cancer (TNBC), mesothelioma, and microsatellite stable (MSS) colorectal cancer. The overall disease control rate, encompassing complete responses, partial responses, and stable disease, was 45% among all participants.

In a subgroup of 19 patients with metastatic or advanced cutaneous melanoma who had previously been treated with PD-1 antibodies, the overall response rate was 47.4%, and the disease control rate reached 68.4%.

Elena Garralda, MD, MSc, Director of Early Drug Development at Vall d’Hebron University Hospital, expressed optimism about FS222's potential. She noted, "Existing immuno-oncology treatments face significant challenges, especially in treatment-resistant cancers. The ability to target multiple immune mechanisms with a single agent like FS222 is an exciting development and addresses a critical unmet need. The results seen in this trial are promising and warrant further investigation."

Ben Toogood, CEO of invoX, echoed these sentiments, stating, "We are encouraged by the preliminary anti-tumor activity of FS222, particularly in melanoma patients previously treated with PD-1 antibodies. There is a pressing need for novel immuno-oncology therapies for patients with treatment-resistant cancers. FS222 shows significant potential in this area, and we are committed to continuing our research to benefit patients in the future."

He further emphasized the broader implications of the trial results, saying, "These findings also validate our antibody platform. We are excited to explore the use of our proprietary CD137-agonist domain from our Fcab® platform in developing additional bispecific antibodies tailored to various tumor types and patient populations."

Enrollment for the phase 1 study of FS222 continues, with ongoing efforts to refine dosing strategies.