May 30, 2023
The Journal of Clinical Oncology (JCO) is pleased to bestow its 2023 Conquer Cancer Young Investigator Award (YIA) on Lanyi Nora Chen, MD, a hematology-oncology fellow at Columbia University. Her research focuses on clinical trial development and experimental therapies as well as outcomes in melanoma and thoracic malignancies.
Dr. Chen has been working on an important project to improve the survival of patients with uveal melanoma (UM), a rare cancer with few effective treatments. She and her colleagues propose to conduct a phase I/II clinical trial of the combination of tebentafusp and hepatic immunoembolization in patients with UM that has spread to the liver, “A phase I/II trial of tebentafusp with hepatic immunoembolization for metastatic uveal melanoma.”
Tebentafusp is a drug that directs immune cells to target and kill UM cells. It gained FDA approval for the treatment of metastatic UM after it improved patient survival in a large randomized clinical trial. Dr. Chen pointed out that since the rate of tumor regression with the drug was low at 9% and only 31% of patients had stable or improved disease at 6 months, many patients have limited to no benefit with tebentafusp alone.
She explained that there is another strategy to treat UM in the liver with hepatic immunoembolization (IE). In this procedure, an immune-activating compound is injected into the liver’s blood supply. This is thought to cause both direct and indirect tumor killing by cutting off tumor blood supply and activating the immune system to target and destroy cancer cells. In previous studies, hepatic IE led to tumor regression in up to 30% of patients. Dr. Chen and her colleagues believe that since both tebentafusp and hepatic IE destroy UM cells by engaging the immune system, they may work synergistically. However, the combination of tebentafusp and hepatic IE has never been studied.
Dr. Chen and her colleagues hypothesize that combination therapy will be safe, feasible, and will increase the percentage of patients with stable or improved disease after 6 months of treatment. While 31% of patients treated with tebentafusp alone had stable or improved disease after 6 months, they expect this to increase to 60% with combination therapy. They will also investigate the effects of treatment on circulating tumor DNA (ctDNA), a potential marker of response to treatment, and study how changes in ctDNA levels correlate with patient survival. Finally, they will study the effects of treatment on markers of inflammation in tumor biopsies and in patient serum.
Dr. Chen and her colleagues expect that treatment will decrease ctDNA levels, increase the number of immune cells within tumors, and increase the levels of inflammatory markers in circulation. The results of their study will improve our understanding of metastatic UM, how it can be treated, and how we can improve outcomes for patients with this disease.
Dr. Chen received her bachelor's degree in molecular biology from Princeton University and completed her medical degree at the University of Pennsylvania, where she was inducted into the Alpha Omega Alpha (AOA) Honor Society. She completed her residency in internal medicine at Columbia University. Her long-term career goal is to become an independent clinical investigator who specializes in clinical trial development for novel therapies in solid tumor malignancies.
Dr. Chen would like to thank JCO and Conquer Cancer, the ASCO Foundation, for their generous support. She would also like to acknowledge the support of her colleagues at Columbia University as well as her research mentors, including Dr. Richard Carvajal and Dr. Marlana Orloff.
First awarded in 1984, the YIA provides funding to promising investigators to encourage and promote quality research in clinical oncology. The purpose of this grant is to fund physicians during the transition from a fellowship program to a faculty appointment. The original idea for JCO to support a YIA came in 1993 from then editor-in-chief George Canellos, MD, while he was also serving as ASCO's president. He saw the award as an opportunity for JCO to encourage promising young researchers to pursue careers in clinical oncology research.