DMMR Cancer

This study intends to explore the role of PD1/PDL1 antibody with selective combination of Sintilimab, IBI310 and Lenvatinib in organ preservation in non-metastatic dMMR/MSI-H gastric or colon cancers with mismatch repair deficiency or high microsatellite instability

This Phase 1, multi-center, open-label, dose escalation and dose optimization study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and preliminary clinical activity of MOMA-341 administered orally as a single agent or combination therapy in patients with microsatellite instability high (MSI-H) or DNA mismatch repair deficiency (dMMR) solid tumors.

Endometrial carcinoma (EC) represents the most common gynecological malignancy in developed countries. Despite therapeutic advances, patients with advanced or recurrent disease still have a poor prognosis, with high recurrence rates and a 5-year survival of less than 20%. Recently, four phase III studies (RUBY, NRG-GY018, AtTEnd, and DUO-E) have demonstrated that the addition of anti-PD-1/PD-L1 immunotherapy to first-line chemotherapy significantly improves progression-free survival, particularly in tumors with altered DNA repair mechanisms known as mismatch repair (MMR) (so-called mismatch repair-deficient or dMMR tumors), but with benefits also observed in a subset of tumors with normal MMR function (so-called MMR-proficient or pMMR tumors). However, despite the clinical approval of these therapies, reliable biomarkers capable of predicting response to immunotherapy are still lacking. This project aims to comprehensively characterize the genomic, epigenetic, and lipid properties of the tumor and the tumor microenvironment (TME) in order to identify predictive markers of response to immunotherapy, thereby laying the foundation for a personalized therapeutic approach in endometrial carcinoma.

This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.