01Jun

Melanoma highlights

While ASCO 2022 is just around the corner, the leading brands in the pharma industry, including Bristol-Myers Squibb, Roche, Amgen, Ascentage Pharma, Iovance Bio, Replimune, Pfizer, etc., are all geared up to present their novel candidates.

The key market players are quite enthusiastic about this indication for treatment. The companies developing different assets anticipate a positive response to these drugs in various lines of treatment.

Abstract Number - 9505

Bristol Myers Squibb to present subgroup analysis from the RELATIVITY-047 trial for the newly approved OPDUALAG for the unresectable or metastatic melanoma patients

Bristol Myers Squibb made history in March by introducing the first LAG-3 drug as part of an Opdivo combo called Opdualag as a treatment for patients with unresectable or metastatic melanoma. BMS’s plan to overcome the patent protection losses of Opdivo has succeeded as the clinical trial results have shown that Opdualag can double the time patients with previously untreated advanced melanoma can live without disease progression compared with Opdivo alone.

Now BMS is planning to further delve into its landmark victory by presenting further data on key subgroups (including those with poorer prognosis) to back its use in various melanoma patients. These results can further help BMS gain positive perception from the KOL’s, establishing Opdualag as a new standard of care as a first-line therapy in melanoma and enhancing its market size.

First-line melanoma is just the first step BMS has planned for Opdualag. The Phase III RELATIVITY-098 trial assesses the Opdivo-plus-relatlimab cocktail versus Opdivo alone in the postsurgery treatment of stages 3–4 melanoma in the adjuvant setting. The company will soon launch a registrational study for the new combo in second-line colorectal cancer.

Abstract Number – 9524

Will the translational data help Iovance to settle the controversy around its most anticipated cell therapy, Lifileucel, in advanced melanoma?

Iovance Therapeutics is all set to submit BLA for its tumor-infiltrating lymphocyte (TIL) cell therapy, Lifileucel, by August 2022 for the treatment of heavily pretreated melanoma patients. The drug has been evaluated in a Phase II trial (NCT02360579) in two Cohorts (Cohort 2 and Cohort 4). The company recently announced the positive Cohort 4 results with a significant ORR of 29% (3CR and 22 PR) and a DOR of 10.4 months after a follow-up of 23.5 months.

However, Iovance has faced a lot of scrutiny from the investors due to comparing these results with the previously announced results of Cohort 2 of the same trial. In the 66-subject cohort, the company saw three complete and 21 partial responses, giving it an objective response rate of 36%. After a median of 33.1 months of follow-up, the study was yet to hit its median duration of response. The cohort still has not reached the median duration of response after 36.6 months.

                Since then, the company has provided multiple explanations for drastic differences. According to Iovance, patients in cohort 4 had more severe disease than those in cohort 2 and higher baseline levels of lactate dehydrogenase (a negative prognostic factor) and higher lesion counts.

Amidst the promising yet controversial results, Inovance Therapeutics will present translational data around tumor mutational burden (TMB) in Lifileucel treated immune checkpoint inhibitor (ICI)-naïve and refractory melanoma patients.

Conclusion

Melanoma accounts for 1.7% of worldwide diagnosed cancer cases and is the fifth most common cancer in the US. Melanoma rates in the United States have doubled in the last two decades, and worldwide, the number of melanoma diagnoses is expected to increase by more than 50% by 2040. Although it attributes to only 20% of all skin cancers, it is the most severe type accounting for ~80% of skin cancer deaths. Patients with melanoma who have been surgically resected and rendered free of disease are still at high risk for relapse. Almost half of the patients are not eligible for immunotherapies, which are the mainstay treatment option. These patients have a poor prognosis and very low survival rates, creating a huge unmet need and offering a huge opportunity for these upcoming drugs.

Several companies have indulged themselves in initiating clinical trials that investigate new treatment options or studying how to use existing treatment options better. Companies like Bristol-Myers Squibb, Roche, Amgen, Ascentage Pharma, Iovance Bio, Replimune and Pfizer, and several others are investigating their key products for managing skin cancers.