Dr. Blank on Predictive Biomarkers in Macroscopic Stage III Melanoma

Christian U. Blank, MD, PhD, a medical oncologist in the Division of Immunology at the Netherlands Cancer Institute, discusses the future of baseline biomarkers in macroscopic stage 3 melanoma.

In the OpACIN trial, investigators compared neoadjuvant ipilimumab (Yervoy) plus nivolumab (Opdivo) with adjuvant ipilimumab plus nivolumab, while the subsequent OpACIN-neo trial evaluated 3 different dosing schedules of neoadjuvant ipilimumab plus nivolumab only. Updated data from the trials were recently presented during the AACR Virtual Meeting II.

For translational analyses from the trial, baseline biomarkers, such as tumor mutational burden (TMB) and interferon gamma expression, were used to predict which patients would have favorable responses to treatment, says Blank. These were found to be independent biomarkers, but if both of these markers were favorable, patients would also have a favorable response, adds Blank. If only 1 of the markers are favorable, either interferon signature high and TMB low or TMB high and interferon signature low, patients still experienced a relatively high response rate. If both biomarkers are low, then patients have a lower response rate; this is a subgroup of patients that will require extended treatment, either with a triplet or alternative treatment to increase response rates, explains Blank.

That effort is being worked on with the phase 1/2 DONIMI trial (NCT04133948), which will examine a neoadjuvant triplet combination versus monotherapy in patients with either low or high interferon signature; this will also examine de-escalated therapy in the patients who have a very high interferon signature.

It is known that a PD-1 inhibitor given by itself can provide a good response, although the percentage of response is low. Therefore, if the optimal patients for this approach can be identified, they also can achieve benefit, says Blank. This is the future of personalized treatment in patients with melanoma: trials examining RNA signature–driven treatments. Through the use of precision medicine, there will be less patients with stage IV disease, concludes Blank.