Nivolumab With PD-L1/IDO Peptide Vaccine Shows Efficacy in Metastatic Melanoma

Encouraging efficacy and survival has been observed in an early-phase study of nivolumab (Opdivo) combined with a PD-L1/IDO peptide vaccine in patients with metastatic melanoma, according to data from a phase 1/2 trial (NCT03047928) presented at the AACR Annual Meeting 2022.¹

At the December 1, 2021, data cutoff date, updated results from the trial showed that among 30 efficacy evaluable patients the overall response rate (ORR) was 80%, and 47% of patients achieved a complete response (CR). At a median follow-up of 2.7 years, the median progression-free survival (PFS) was 25.3 months, and the median overall survival (OS) was not reached.

The trial enrolled patients with stage IV melanoma who had not been previously treated with an anti-PD-1 therapy. Patients received the anti-PD-1 antibody nivolumab at a dose of 3 mg/kg every 2 weeks for up to 2 years. Investigators administered the IDO/PD-L1 peptide vaccine subcutaneously for up to 15 doses: 1 dose every 2 weeks for a total of 6 doses and 1 dose every 4 weeks for a total of 9 doses. Responding patients stayed on nivolumab at a dose of 6 mg/kg administered every 4 weeks after the vaccine series was completed.

The primary end point of the trial was feasibility and safety. Secondary end points included ORR, OS, and PFS.²

The median age of patients in the trial was 70 (range, 46-85) and most were males (55%). A majority of patients had BRAF wild-type disease (63%) and 17 (57%) patients had PD-L1 expression greater than 1%.

A subgroup analysis showed that among patients with M1a or M1b stage disease (n = 13) achieved an ORR of 69%, including a 46% CR rate. Patients with M1c stage disease (n = 17) performed even better, displaying an ORR of 88% and a CR rate of 47%. The median PFS was 14.8 months and 25.6 months for patients with M1a/M1b stage disease or M1c stage disease, respectively.

PD-L1-positive patients (> 1%) experienced an ORR of 94% and a median PFS of 30.9 months. Patients who were PD–L1-negative at the time of enrollment (n = 13) achieved an ORR of 61.5% and a median PFS of 7.2 months. CR rates were 53% and 38.5%, respectively.

In terms of LDH status, patients with non-elevated LDH levels had an ORR of 79% compared with 82% among patients who had elevated LDH. The median PFS was 19.3 months and 30.9 months, respectively. Most patients in the non-elevated LDH group achieved a CR (53%) compared with 36.5% of patients in the elevated LDH group.

Regarding safety investigators noted that the incidence of immune-related adverse events was comparable to that of patients who received nivolumab monotherapy. No additional toxicity was reported among patients who were deemed to have a poor prognosis.

“Patients with unfavorable prognostic baseline characteristics obtained impressive response rates and durable responses without additional toxicity,” study authors wrote. “A phase 3 clinical trial [NCT05155254] investigating IDO/PD-L1 and pembrolizumab [Keytruda] is open for enrollment to validate the data in a larger population.”

_References

_{1. Kjeldsen JW, Lorentzen CL, Martinenaite E, et al. High clinical efficacy in poor prognosis patients with metastatic melanoma treated with an IDO/PD-L1 peptide vaccine in combination with nivolumab. Poster presented at: 2022 AACR Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT535.}

_{2. Kjeldsen JW, Lorentzen CL, Martinenaite E, et al. A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. Nat Med. 2021;27(12):2212–2223. doi:10.1038/s41591-021-01544-x}