Promising Front-Line Treatment Options for Metastatic Melanoma
<ѻý class="mpt-content-deck">– CR rate of 34.2% in phase II PIVOT-02 study of BEMPEG plus nivolumab is encouraging as a future optionѻý>This Reading Room is a collaboration between ѻý® and:
After the initial landmark treatment advances in metastatic melanoma with ipilimumab (ipi), nivolumab (nivo), and targeted therapy, there has been a paucity of effective new therapeutic advances. Over the past 6 months, however, data have emerged for several promising front-line treatment options.
Bempegaldesleukin (BEMPEG), a CD122 preferential IL-2 pathway agonist, in combination with nivolumab demonstrated a 34.2% complete response (CR) rate in the front-line setting for metastatic melanoma in the . We await results from the phase III study, but one in three patients achieving a CR is encouraging as a future option. This compares with a 22% CR rate reported with ipi/nivo in CheckMate 067.
Changing the treatment paradigm in the front-line setting will require a treatment to achieve a higher response rate, including a higher CR rate, than ipi/nivo or to achieve sustained efficacy with improved toxicity. Combination therapy with ipi/nivo recently demonstrated a 49% overall survival rate at 6 and a half years, setting a high bar for future first-line therapies.
The front-line debate will soon include relatlimab (a LAG3 inhibitor) with nivo from the RELATIVITY-047 phase III study that demonstrated a progression-free-survival benefit in treatment-naïve patients compared with single-agent nivo. Response rate and overall survival data, however, have not yet been reported, so it is too soon for a full comparison.
There are many questions yet to answer in the front-line setting for new therapies. Will BEMPEG with nivolumab demonstrate benefit in a randomized phase III study? Will toxicity prove to be more manageable than ipi/nivo? Are either BEMPEG or relatlimab in combination with nivo efficacious in patients with brain metastases?
With multiple current front-line approvals in metastatic melanoma and more promising agents potentially headed into the line-up, biomarker analyses will be increasingly important. BRAFV600 patients have significant benefit from combination ipi/nivo compared with single-agent anti PD-1, but this same benefit is not seen in BRAF wild-type patients.
Predictive immune biomarkers remain elusive. PIVOT-02 performed extensive exploratory translational studies and did establish several immune markers consistent with response such as high IFN-γ gene expression profiling and high CD8+ tumor-infiltrating lymphocytes; however, the phase III study will shed more light on the utility of these markers.
A consistent predictive biomarker would aid clinicians and patients in the increasingly complex decision-making process, but until testing is available, decisions will be based on toxicities, disease volume, and comorbidities.
Meredith McKean, MD, MPH, is a clinical investigator in the Melanoma and Skin Cancer Research Program at Sarah Cannon Research Institute, Tennessee Oncology, in Nashville.
Read the study here and an interview about it here.
Primary Source
Journal of Clinical Oncology
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