DYP688 / Novartis - LARVOL DELTA

A first-in-human study of DYP688, an antibody drug conjugate delivering a direct Gq/11 inhibitor, in patients with metastatic uveal melanoma (MUM) and other GNAQ/11 mutant melanomas. (ASCO 2025) - P1/2 | "SDZ475 (FR900359) is a potent GNAQ/11 inhibitor, however in vivo toxicity has precluded clinical development...Of the 66 treated pts, 60 (90.9%) had prior antineoplastic therapy; 38 (57.6%) received ≥2 lines, and 22 (33.3%) received prior tebentafusp... DYP688 shows favorable safety and tolerability at all doses tested and promising preliminary clinical efficacy at doses ≥ 12mg/kg Q2W; the RDs for dose optimization are yet to be declared and dose exploration is ongoing."

Clinical • Metastases • P1 data • Anemia • Endocrine Disorders • Eye Cancer • Fatigue • Hematological Disorders • Hypotension • Melanoma • Metabolic Disorders • Oncology • Solid Tumor • Uveal Melanoma • Xerostomia • GNAQ • PMEL

QSP modeling of a transiently inactivating antibody-drug conjugate highlights benefit of short antibody half life. (PubMed, J Pharmacokinet Pharmacodyn) - "DYP688 is a novel ADC comprising of a signaling protein inhibitor payload (FR900359) that undergoes unique on-antibody inactivation in plasma, resulting in complex pharmacology. Finally, we performed the successful preclinical to clinical translation of DYP688 PK, including the payload inactivation kinetics, evidenced by good agreement of the predicted PK to the observed interim clinical PK. Overall, this work highlights early quantitative pharmacokinetics as a missing link in the ADC design-developability chasm."

Journal • Oncology

Real world experience of molecular landscape of uveal melanomas: Implications for personalized medicine strategies. (ASCO 2024) - "GNAQ/GNA11 mutations are known to activate the MAPK/ERK signaling pathway, contributing to uncontrolled cell proliferation; its presence qualifies for entry into clinical trial testing DYP688 in metastatic UM... These findings underscore the need for a comprehensive genomic approach in guiding therapeutic decisions, understanding prognostic implications and advancing personalized medicine strategies for UM patients. Our study provides an overview of the molecular landscape of UMs with delineation of key molecular features, thereby enhancing our understanding of UM biology and setting the stage for the development of targeted therapies tailored to the unique genomic profile of each patient."

Clinical • IO biomarker • Real-world • Real-world evidence • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1 • BRCA • EIF1AX • GNA11 • GNAQ • HRD • PD-L1 • PRAME • SF3B1 • TMB

A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Mar 2026 ➔ Sep 2025 | Trial primary completion date: Mar 2026 ➔ Sep 2025

Metastases • Trial completion date • Trial primary completion date • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • GNAQ

A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Nov 2025 ➔ Mar 2026 | Trial primary completion date: Nov 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • GNAQ

A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • GNAQ

A Phase I/II study of DYP688 treatment alone in patients with eye cancer and other types of cancers of the skin and mucosal membranes in the body (clinicaltrialsregister.eu) - P1/2 | N=124 | Sponsor: Novartis Pharma AG

New P1/2 trial • Eye Cancer • Melanoma • Mucosal Melanoma • Ocular Melanoma • Oncology • Skin Cancer • Solid Tumor • Uveal Melanoma • GNAQ

A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas (clinicaltrials.gov) - P1/2 | N=124 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • GNAQ