Dr. Pavlick on Addressing Unmet Needs in Melanoma Through Ongoing Investigation

Anna C. Pavlick, DO, professor of medicine, the Division of Hematology and Medical Oncology, Weill Cornell Medicine, founding director, the Cutaneous Oncology Program, Weill Cornell Medicine and New York-Presbyterian, discusses how ongoing research efforts at Weill Cornell Medicine are attempting to ameliorate unmet needs in melanoma.

Melanoma subtypes are characterized by several distinct, somatic mutations, Pavlick begins. Although BRAF mutations are most observed and targeted in therapeutic development, a large proportion of patients exhibit NRAS mutations, she states. However, these patients often exhibit decreased or less durable responses to immunotherapies, and often progress later in the disease course, Pavlick explains. There is a subsequent lack of interest in developing effective targeted therapies that target NRAS, Pavlick adds.

To address this unmet need, researchers at Weill Cornell Medicine designed a trial to evaluate an oral agent for patients with NRAS mutations, Pavlick details. This trial may advance interest in developing targeted therapeutics for this underserved population, she says.

Ongoing research at Weill Cornell is also focused on improving upon current regimens for patients with stage II melanoma, Pavlick continues. This patient population is considered high-risk, she notes. Previous research has demonstrated that these patients can benefit from single-agent anti–PD-1 therapy, but the effect of dual checkpoint inhibitor combinations has not yet been investigated in this population, Pavlick states. An adjuvant study comparing the efficacy of PD-1 inhibitor monotherapy vs PD-1 inhibition in combination with a TIGIT-targeting checkpoint inhibitor is currently being conducted.

Lastly, there is increased interest in investigating the use of tumor-infiltrating lymphocyte treatment in stage IV melanoma, Pavlick states. This approach requires a patient’s tumor to be harvested, and infiltrating T cells are then extracted. These T cells then undergo proliferation in a laboratory and are re-administered to the patient. This could improve patients’ disease status as well as their immune responses, Pavlick concludes.