LBA48 - Clinical efficacy and immunity of combination therapy with nivolumab and IDO/PD-L1 peptide vaccine in patients with metastatic melanoma: A phase I/II trial

Background

The IDO/PD-L1 (IO102/IO103)¹ peptide vaccine is a first-in-class immunomodulatory vaccine containing single IDO- and PD-L1-derived long peptide sequences designed to engage and activate IDO and PD-L1 specific T-cells mediating immune switch. This non-randomized phase I/II study evaluates the IDO/PD-L1 peptide vaccine in combination with nivolumab in patients with progressive metastatic melanoma. Here we report safety, efficacy, and immune response data.

Methods

Thirty treatment naive stage IV melanoma patients received a maximum of 15 IDO/PD-L1 vaccine doses SC (6x q2w followed by 9x q4w). Nivolumab (3 mg/kg) was administered every second week (q2w) until intolerable toxicity or tumor progression. The objectives were to assess safety, immune response in blood and biopsies as well as efficacy.

Results

As of the data cut-off, August 2020, all 30 patients were enrolled with a median follow up of 15 months. 1 patient is pending first evaluation, 29 were evaluated and by investigator review per RECIST v1.1 an overall response rate (ORR) of 79% was reached; ORR was 94% and 62% in PD-L1 positive and negative patients, respectively. At data cut-off, 45% have reached complete response and 34% partial response, which was significantly higher than a matched control group extracted from the DAMMED database receiving anti-PD-1 monotherapy treatment as standard of care. The median progression free survival (mPFS) was 25,6 months. Except for local reactions at vaccination site toxicity was comparable to patients receiving nivolumab monotherapy. Vaccine specific T-cells against either IDO and/or PD-L1 were detectable in PBMC from all treated patients and in a number of patients at the tumor site where a biopsy was feasible. Preliminary results from tumor immune contexture analyses were indicative for response.

Conclusions

The combination of IDO/PD-L1 peptide vaccine and nivolumab is safe with encouraging early efficacy data; an ORR of 79% was reached and 45% achieved complete response. Vaccine specific T-cells were demonstrated in PBMCs and tumor site. ClinicalTrials.gov Identifier: NCT03047928 ¹ IO Biotech (www.iobiotech.com) has licensed the patent of the vaccine IO102/IO103 T-win®.

Clinical trial identification

NCT03047928.

Editorial acknowledgement

Legal entity responsible for the study

Inge Marie Svane.

Funding

Has not received any funding.

Disclosure

I-M. Svane: Advisory/Consultancy, Shareholder/Stockholder/Stock options, Officer/Board of Directors: IO Biotech; Honoraria (self): BMS; Honoraria (self), Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Honoraria (self): AbbVie; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self): Sanofi Genzyme; Honoraria (self): Ipsen; Advisory/Consultancy: InCyte; Honoraria (self): Merch; Honoraria (self): Roche; Advisory/Consultancy: Celgene. M.H. Andersen: Shareholder/Stockholder/Stock options, Officer/Board of Directors: IO Biotech. All other authors have declared no conflicts of interest.