An open-label, randomized, phase I/II trial of IO102 and pembrolizumab, or IO102, pembrolizumab and chemotherapy, as first-line treatment for patients with metastatic non-small cell lung cancer
Authors: J. Spicer, M. Provencio, P. Garrido Lopez, J. Bosch-Barrera, F.J. de Castro Carpeño, E. Felip, J. Trigo, S. Viteri, E. Coart, E. Schmidt, A.V. Christiansen, M.-B. Zocca, M.H. Andersen, E. Ehrnrooth, L. Paz-Ares
Journal: Annals of Oncology (2019)

Background: Immunotherapy has significantly changed the treatment landscape of non-small cell lung cancer (NSCLC) with no driver mutations. However, despite the addition of anti-PD-1/PD-L1 therapies to the clinical armamentarium only a subset of patients derives durable benefit. IO102 is a novel, second generation, HLA-A unrestricted immune modulating T-win® vaccine targeting IDO. IO102 has a dual mode of action; remodulation of the tumour micro-environment through elimination of immune suppressive cells and induction of CD8 T-cell mediated killing of IDO-expressing tumor cells. Our first-generation IDO vaccine (IO101) has shown promising antitumor activity and a favorable safety in heavily pretreated NSCLC patients (Iversen, CCR 2013). Trial design: Phase I/II, international, multicenter, open-label, randomized trial with two parallel cohorts. Cohort A: IO102 (100µg s.c.) and pembrolizumab (200 mg) (PD-L1 ≥ 50%); Cohort B: IO102, pembrolizumab and carboplatin plus pemetrexed (PD-L1 < 50%). The maximum treatment duration is 35 cycles (app. 2 years). Key eligibility criteria include metastatic NSCLC or non-squamous NSCLC (cohort B) with no prior treatment for metastatic NSCLC and no driver mutations. Phase I is a non-randomized safety run-in with 6 patients per cohort investigating one dose level of the experimental arms. Only one DLT is allowed in each cohort. Phase II is following Sargent's two-stage, three-outcome optimum design (Sargent, ClinTrial2001) with a 2:1 randomization in the cohorts. Cohort A: IO102 and pembrolizumab versus pembrolizumab alone; Cohort B: IO102, pembrolizumab and chemotherapy vs. pembrolizumab and chemotherapy. Provision of blood and tumour tissue is required for biomarker studies. The primary endpoint is safety and objective response rate (ORR) per RECIST 1.1 in Phases I and II, respectively. Secondary endpoints include ORR per iRECIST, duration of response, progression free survival, overall survival, and biomarkers including immunoscore in tissue, tumour mutational burden and immunomonitoring in blood. The study is enrolling in Europe and US: EudraCT Number 2018-000139-28 / IND Number 018081. Clinical trial identification: EudraCT 2018-000139-28 / IND Number: 018081. Legal entity responsible for the study: IO Biotech. Funding: IO Biotech. Disclosure: J. Spicer: Research funding, honoraria (institutional): Achilles, AstraZeneca, Bayer, BerGenBio, Boehringer Ingelheim, BMS, Celgene, Curis; Genmab, Roche, Shionogi, Starpharma, Taiho; Co-founder, shareholder: IGEM Therapeutics. P. Garrido Lopez: Consulting, advisory: I4, MSD, BMS, Boerhinger Ingelheim, Pfizer, AbbVie, Guardant Health, Novartis, Lilly, AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaker: Roche, MSD, BMS, Pfizer, Novartis, Boerhinger Ingelheim. J. Bosch-Barrera: Advisory board: MSD. E. Felip: Advisory: Blue Print Medicines, Celgene, Guardant Health, Janssen; Advisory, speaker: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda; Consultant: Boehringer Ingelheim. J. Trigo: Advisory board: Takeda, BMS, Boehringer; Speaker: BMS, Boehringer, Roche, AstraZeneca. S. Viteri: Speaker fees: BMS, Roche; Travel fees: Servier, Roche, Merck Serono; Advisory fees: Roche, AbbVie; Research fees: Roche, BMS, Servier, Merck Serono, AbbVie, Janssen. E. Schmidt: Employed: Merck & Co., Inc. A.V. Christiansen, E. Ehrnrooth: Employed: IO Biotech; Member of the Safety Monitoring Committee for the IO102-012/KN-764 trial. M-B. Zocca: Chief Executive Officer, founder: IO Biotech; Member of the Safety Monitoring Committee for the IO102-012/KN-764 trial. M.H. Andersen: Chief Scientific Officer, founder, member of BoD: IO Biotech. L. Paz-Ares: Advisory board: Roche, Lily, MSD, BMS, Boehringer Ingelheim, Novartis, AstraZeneca, Amgen, Pfizer. All other authors have declared no conflicts of interest.