A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma
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A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. / Kjeldsen, Julie Westerlin; Lorentzen, Cathrine Lund; Martinenaite, Evelina; Ellebaek, Eva; Donia, Marco; Holmstroem, Rikke Boedker; Klausen, Tobias Wirenfeldt; Madsen, Cecilie Oelvang; Ahmed, Shamaila Munir; Weis-Banke, Stine Emilie; Holmström, Morten Orebo; Hendel, Helle Westergren; Ehrnrooth, Eva; Zocca, Mai Britt; Pedersen, Ayako Wakatsuki; Andersen, Mads Hald; Svane, Inge Marie.
In: Nature Medicine, Vol. 27, 2021, p. pages2212–2223.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma
AU - Kjeldsen, Julie Westerlin
AU - Lorentzen, Cathrine Lund
AU - Martinenaite, Evelina
AU - Ellebaek, Eva
AU - Donia, Marco
AU - Holmstroem, Rikke Boedker
AU - Klausen, Tobias Wirenfeldt
AU - Madsen, Cecilie Oelvang
AU - Ahmed, Shamaila Munir
AU - Weis-Banke, Stine Emilie
AU - Holmström, Morten Orebo
AU - Hendel, Helle Westergren
AU - Ehrnrooth, Eva
AU - Zocca, Mai Britt
AU - Pedersen, Ayako Wakatsuki
AU - Andersen, Mads Hald
AU - Svane, Inge Marie
N1 - Correction: https://doi.org/10.1038/s41591-022-01771-w Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021
Y1 - 2021
N2 - Anti-programmed death (PD)-1 (aPD1) therapy is an effective treatment for metastatic melanoma (MM); however, over 50% of patients progress due to resistance. We tested a first-in-class immune-modulatory vaccine (IO102/IO103) against indoleamine 2,3-dioxygenase (IDO) and PD ligand 1 (PD-L1), targeting immunosuppressive cells and tumor cells expressing IDO and/or PD-L1 (IDO/PD-L1), combined with nivolumab. Thirty aPD1 therapy-naive patients with MM were treated in a phase 1/2 study (https://clinicaltrials.gov/, NCT03047928). The primary endpoint was feasibility and safety; the systemic toxicity profile was comparable to that of nivolumab monotherapy. Secondary endpoints were efficacy and immunogenicity; an objective response rate (ORR) of 80% (confidence interval (CI), 62.7–90.5%) was reached, with 43% (CI, 27.4–60.8%) complete responses. After a median follow-up of 22.9 months, the median progression-free survival (PFS) was 26 months (CI, 15.4–69 months). Median overall survival (OS) was not reached. Vaccine-specific responses assessed in vitro were detected in the blood of >93% of patients during vaccination. Vaccine-reactive T cells comprised CD4+ and CD8+ T cells with activity against IDO- and PD-L1-expressing cancer and immune cells. T cell influx of peripherally expanded T cells into tumor sites was observed in responding patients, and general enrichment of IDO- and PD-L1-specific clones after treatment was documented. These clinical efficacy and favorable safety data support further validation in a larger randomized trial to confirm the clinical potential of this immunomodulating approach.
AB - Anti-programmed death (PD)-1 (aPD1) therapy is an effective treatment for metastatic melanoma (MM); however, over 50% of patients progress due to resistance. We tested a first-in-class immune-modulatory vaccine (IO102/IO103) against indoleamine 2,3-dioxygenase (IDO) and PD ligand 1 (PD-L1), targeting immunosuppressive cells and tumor cells expressing IDO and/or PD-L1 (IDO/PD-L1), combined with nivolumab. Thirty aPD1 therapy-naive patients with MM were treated in a phase 1/2 study (https://clinicaltrials.gov/, NCT03047928). The primary endpoint was feasibility and safety; the systemic toxicity profile was comparable to that of nivolumab monotherapy. Secondary endpoints were efficacy and immunogenicity; an objective response rate (ORR) of 80% (confidence interval (CI), 62.7–90.5%) was reached, with 43% (CI, 27.4–60.8%) complete responses. After a median follow-up of 22.9 months, the median progression-free survival (PFS) was 26 months (CI, 15.4–69 months). Median overall survival (OS) was not reached. Vaccine-specific responses assessed in vitro were detected in the blood of >93% of patients during vaccination. Vaccine-reactive T cells comprised CD4+ and CD8+ T cells with activity against IDO- and PD-L1-expressing cancer and immune cells. T cell influx of peripherally expanded T cells into tumor sites was observed in responding patients, and general enrichment of IDO- and PD-L1-specific clones after treatment was documented. These clinical efficacy and favorable safety data support further validation in a larger randomized trial to confirm the clinical potential of this immunomodulating approach.
U2 - 10.1038/s41591-021-01544-x
DO - 10.1038/s41591-021-01544-x
M3 - Journal article
C2 - 34887574
AN - SCOPUS:85120935004
VL - 27
SP - 2212
EP - 2223
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
ER -
ID: 287764020