Northwell Scientists Report Phase 1 Success for Novel Uveal Melanoma ADC DYP688

Researchers at Northwell Health's Feinstein Institutes for Medical Research announced findings from a phase 1 clinical trial of DYP688, a first-in-class drug designed to treat metastatic uveal melanoma (UM), published in Nature Medicine.¹ The trial results showed disease control in more than 80% of patients and cancer shrinkage in nearly 20% of patients, while also successfully mitigating severe systemic toxicities.¹ The drug demonstrated measurable anti-tumor activity and was well tolerated overall.¹

Richard D. Carvajal, MD, deputy physician-in-chief and director of medical oncology at the Northwell Health Cancer Institute and the Roy J. and Tara Zuckerberg Professor in Medical Oncology, who helped lead the study, said, "This first-in-class antibody-drug conjugate is a smart, targeted therapy designed to kill only diseased cells, a novel approach that differs from conventional cytotoxic drugs. In this study, we observed promising results alongside an exceptionally high degree of patient tolerability. While Novartis has made a business decision to halt its development, the academic and patient communities recognize its potential."¹

How does DYP688 work?

DYP688 is an antibody-drug conjugate (ADC) that pairs targeted delivery with a Gq/11 pathway inhibitor rather than the broadly cytotoxic chemotherapy payloads carried by many conventional ADCs.¹ UM is almost universally driven by mutations in the Gq/11 signaling pathway, making it a well-defined, biomarker-selected target for this kind of precision approach.¹ Unlike ADCs designed to kill any cell they encounter, DYP688 is built to identify diseased cells specifically and block the cancer's growth pathway directly.¹

Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes and the Karches Family Distinguished Chair in Medical Research, said, "Precision medicine is the key to better treatment. Dr. Carvajal's leadership in completing this trial demonstrates the importance of rigorous research and will hopefully inspire future investigation into this treatment."¹

Why does this disease represent such a significant unmet need?

UM is a severe cancer originating in the eye that most commonly spreads to the liver, making it exceptionally difficult to treat once metastatic; patients with metastatic disease often face a survival rate of less than two years.¹ Established treatment options remain limited for this population, and the disease represents a major unmet medical need with few effective systemic therapies available.¹ Immunocore's tebentafusp, a bispecific T-cell receptor therapy, is one of the few other treatments to demonstrate a meaningful survival benefit in this same metastatic UM population.²

In a previous interview with BioPharm International, Alexander Shoushtari, MD, a melanoma oncologist and cellular therapist at Memorial Sloan Kettering Cancer Center, said of the five-year tebentafusp data, "I think what this trial has really shown is that you have to get more precise as a scientist, and you have to be more aware as a physician that different tools now exist to manipulate the body's immune system to fight cancer."³ That same precision principle, targeting UM's well-defined Gq/11 pathway rather than relying on broader immune activation, is central to DYP688's design as well.¹

Why does this trial matter despite Novartis halting development?

Novartis has made a business decision to discontinue DYP688's development, a decision Carvajal directly addressed in discussing the trial results.¹ Despite that discontinuation, the academic and patient communities have recognized the drug's potential based on the Phase 1 findings.¹

What happens next?

With Phase 1 results now published in a peer-reviewed journal, the path forward for DYP688 itself is uncertain given Novartis's decision to halt development. However, the results add clinical validation to Gq/11-targeted ADC approaches in UM more broadly, potentially informing future academic or industry efforts to advance similar mechanisms in this historically difficult-to-treat cancer.

References

1. Northwell Scientist Reveals Breakthrough Results in Eye Cancer Drug. (2026 Jul 24). BusinessWire. https://www.businesswire.com/news/home/20260724476580/en/Northwell-Scientist-Reveals-Breakthrough-Results-in-Eye-Cancer-Drug
2. Mirasol F. (2026 April 20). Tebentafusp Shows Durable Survival in Metastatic Uveal Melanoma, Immunocore Reports. BioPharm International. https://www.biopharminternational.com/view/tebentafusp-shows-durable-survival-in-metastatic-uveal-melanoma-immunocore-reports
3. Shoushtari A, Schoenthaler E. (2026 May 29). Kimmtrak Data Challenge Long-Held Assumptions About Immunotherapy in Uveal Melanoma. https://www.biopharminternational.com/view/kimmtrak-data-challenge-long-held-assumptions-about-immunotherapy-in-uveal-melanoma