Analyst answers — What lies ahead for malignant melanoma?

What changes do key opinion leaders (KOLs) see coming for malignant melanoma (MM) treatment? We sat down with lead KOL Insights analyst Basharut Syed to discuss his research into recent developments and what new therapies have potential to influence the treatment landscape in the next three-to-five years. Here he shares some key findings from recent in-depth interviews with KOLs on the topic.

FirstWord: What was the main objective for this research?

Basharut Syed: The introduction of novel targeted systemic therapies has provided oncologists with valuable interventions for the treatment of MM; however, there is still a great demand for improved therapeutic options. Our research was concentrated on key advances in mid-to late-stage pipeline that could potentially impact the treatment landscape for MM in the near future. Novel small-molecule and biologic therapies are progressing through late-stage development, but which products will stand out? Who will be the key players? Where are the most important opportunities and threats for investors in this area?

FW: Based on the research, what is the general sentiment from KOLs on the progression of the treatment landscape for MM?

BS: KOLs are excited by the progress in the field of melanoma, as a wide array of drugs have expanded the arsenal of treatments options for patients. These agents have greatly improved the three-year- survival rates for a larger number of late-stage patients, but, even with the most recent advances, there are still many patients who do not benefit. In the near-future, KOLs are optimistic about the combination of BRAF/MEK agents with the checkpoint inhibitors and believe they could move the field forward by playing a role in melanoma.

FW: What is one of the most notable changes over the last few months in MM treatment your research has found?

BS: In September 2018, Nektar and Bristol-Myers Squibb initiated a registrational Phase III trial for its lead immuno-oncology candidate, the CD122-biased agonist NKTR-214, in combination with nivolumab, in previously untreated melanoma patients. The open-label, randomised trial is enrolling approximately 764 patients and follows promising Phase II Pivot-02 trial data.

FW: What was one of the most insightful KOL interview quotes? What did it teach us?

BS: "I think the immune checkpoint [inhibitors], for which we don't yet have adequate data, is another key area that needs to be explored. Obviously, immune checkpoints have had a major impact [success] in melanoma, but we've only looked at two of them and there are another 10 others, so we need to explore those as well." [European KOL]

KOLs point to the tremendous success with blockade of programmed cell death 1 (PD-1) with Keytruda (pembrolizumab) and Opdivo (nivolumab), and the anti-cytotoxic T lymphocyte antigen (CTLA)-4 agent Yervoy (ipilimumab), but they stress that other immune checkpoints need to be explored. Now, there is intense focus to evaluate drugs that inhibit multiple checkpoints or co-inhibitory receptors, beyond the CTLA-4 and PD-1 axis that opinion leaders hope will possibly provide a significant breakthrough. These include Bristol-Myers Squibb and Ono’s relatlimab, that targets lymphocyte activation gene 3–encoded protein (LAG3), being trialled with Opdivo.