Dr Khushalani on Fixed-Dose Treatment Regimens in Advanced Melanoma

Nikhil Khushalani, MD, vice chair, Department of Cutaneous Oncology, Moffitt Cancer Center, discusses the benefits and limitations of fixed-dose treatment regimens, such as the combination of fianlimab (formerly REGN 3767) and cemiplimab-rwlc (Libtayo) that is under investigation in the phase 3 HARMONY HEAD TO HEAD trial (NCT06246916) in patients with unresectable or metastatic melanoma.

One advantage of fixed-dose treatment regimens is their convenience, as they are administered from a single vial, and no dose variability exists between patients, Khushalani says. This uniformity simplifies the treatment process, Khushalani notes. However, one notable disadvantage of this type of regimen is the inherent difficulty in identifying the specific agent responsible for any treatment-related toxicities that may arise, Khushalani explains. Accordingly, when patients develop toxicities, it can be difficult to determine which of the 2 agents should be discontinued to try to mitigate the toxicity, Khushalani emphasizes.

For example, the combination of ipilimumab (Yervoy) plus nivolumab (Opdivo) is commonly used for the treatment of patients with melanoma, Khushalani adds. If a patient develops a grade 3 or higher toxicity while receiving this regimen, oncologists often decide to discontinue ipilimumab and continue to administer nivolumab, according to Khushalani. However, if patients receiving a fixed-dose combination regimen require discontinuation of 1 agent, the fixed-dose combination would need to be discontinued entirely. Then the patient may continue to receive 1 of the agents as monotherapy, Khushalani concludes.

The ongoing HARMONY HEAD TO HEAD trial is evaluating a fixed-dose combination of fianlimab plus cemiplimab vs the fixed-dose combination of relatlimab plus nivolumab (Opdualag) in patients with unresectable or metastatic melanoma who have not received frontline therapy for advanced melanoma. Overall response rate serves as the trial’s primary end point. Key secondary end points include progression-free survival and overall survival. Other secondary end points include duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity.