CAMBRIDGE, UK, May 19, 2026
Mestag Therapeutics announced the first patient has been dosed in the Phase 1 STARLYS clinical trial evaluating MST-0312, a novel bispecific antibody designed to activate the lymphotoxin-beta receptor (LTBR) pathway in advanced solid tumors. The first-in-human study will investigate MST-0312 both as a monotherapy and in combination with Keytruda® (pembrolizumab) in patients with selected advanced cancers. The company aims to evaluate the therapy’s ability to induce tertiary lymphoid structures (TLS) and high endothelial venules (HEV) within tumors, a strategy intended to improve immune cell recruitment and enhance anti-tumor immune responses. The milestone positions Mestag Therapeutics among a growing group of biotechnology companies developing next-generation immuno-oncology therapies designed to reshape the tumor microenvironment rather than targeting tumor cells directly.
MST-0312 Designed to Activate Anti-Tumor Immunity
MST-0312 is a targeted LTBR agonist bispecific antibody engineered to stimulate formation of TLS and HEV inside tumors. These immune structures are increasingly recognized as important biological markers associated with improved anti-cancer immune activity, stronger treatment responses, and extended patient survival across multiple cancer types. TLS contain organized collections of T cells, B cells, and dendritic cells that help recruit and activate immune responses directly within tumor tissue.
The STARLYS trial will initially focus on solid tumors arising in barrier organs, including lung, gut, bladder, breast, and skin cancers, where researchers believe TLS formation may be particularly beneficial. The adaptive, open-label Phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of MST-0312 across multiple treatment arms. Researchers will also investigate whether combining MST-0312 with pembrolizumab can further enhance immune activation in tumors that are either immunologically “cold” or “warm.”
According to Mestag Therapeutics Chief Medical Officer Dr. Lindsey Rolfe, the study was intentionally designed to generate both mechanistic and clinical insights that could guide future development of this new therapeutic class. The company believes targeting fibroblast immunology and tumor immune architecture may help overcome resistance mechanisms limiting the effectiveness of current checkpoint inhibitor therapies.
STARLYS Trial Explores Novel Immunotherapy Strategy
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The first patient in the STARLYS trial was dosed at START Madrid-CIOCC in Spain under Principal Investigator Dr. Emiliano Calvo, while the broader study is being coordinated by Dr. Elena Garralda of the Vall d’Hebron Institute of Oncology in Barcelona. Investigators emphasized that many patients with advanced solid tumors continue to receive limited benefit from currently available immunotherapies, particularly in tumors lacking sufficient immune infiltration..
Published research has shown that tumors containing TLS and HEV structures are associated with significantly improved responses to treatment and longer survival outcomes compared to tumors where these immune structures are absent. By directly stimulating LTBR signaling within the tumor microenvironment, MST-0312 is designed to actively induce these structures and potentially convert poorly responsive tumors into immune-active environments more susceptible to immunotherapy.
The trial reflects broader industry efforts to develop next-generation cancer immunotherapies that go beyond PD-1 or PD-L1 checkpoint blockade by remodeling tumor immune biology itself. If successful, MST-0312 could establish a new immunological strategy for treating solid tumors by enhancing localized immune organization and activation inside cancer tissue.
Mestag Expands Fibroblast Immunology Platform in Oncology
Mestag Therapeutics is focused on leveraging fibroblast immunology to develop therapies for cancer and inflammatory diseases. Fibroblasts play a critical role in shaping the tumor microenvironment, influencing immune cell recruitment, tissue remodeling, and treatment resistance. Through its platform, Mestag aims to identify mechanisms capable of converting immune-suppressed tumors into environments more responsive to anti-cancer therapies.
The initiation of the STARLYS trial marks a significant transition for the company into clinical-stage development. By evaluating both biological effects and clinical responses in diverse solid tumor populations, Mestag hopes to validate LTBR activation as a potentially important new pathway in cancer immunotherapy. Positive findings from the study could support future expansion into additional tumor types and combination regimens involving checkpoint inhibitors or other immuno-oncology agents.
Source: Mestag Therapeutics press release
