Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab
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Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. / Lorentzen, Cathrine Lund; Kjeldsen, Julie Westerlin; Ehrnrooth, Eva; Andersen, Mads Hald; Marie Svane, Inge.
I: Journal for ImmunoTherapy of Cancer, Bind 11, Nr. 5, e006755, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab
AU - Lorentzen, Cathrine Lund
AU - Kjeldsen, Julie Westerlin
AU - Ehrnrooth, Eva
AU - Andersen, Mads Hald
AU - Marie Svane, Inge
N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023
Y1 - 2023
N2 - Background We have previously published initial efficacy of the indoleamine 2,3-dioxygenase (IDO)/anti-programmed death ligand 1 (PD-L1) vaccine in combination with nivolumab in 30 anti-PD-1 therapy naïve patients with metastatic melanoma (cohort A). We now report long-term follow-up of patients in cohort A. Further, we report results from cohort B, where the peptide vaccine was added to anti-PD-1 therapy for patients with progressive disease during anti-PD-1 treatment. Methods All patients were treated with a therapeutic peptide vaccine in Montanide targeting IDO and PD-L1 combined with nivolumab (NCT03047928). A long-term follow-up of safety, response rates, and survival rates were performed in cohort A including patient subgroup analyses. Safety and clinical responses were analyzed for cohort B. Results Cohort A: At data cut-off, January 5, 2023, the overall response rate (ORR) was 80%, and 50% of the 30 patients obtained a complete response (CR). The median progression-free survival (mPFS) was 25.5 months (95% CI 8.8 to 39), and median overall survival (mOS) was not reached (NR) (95% CI 36.4 to NR). The minimum follow-up time was 29.8 months, and the median follow-up was 45.3 months (IQR 34.8-59.2). A subgroup evaluation further revealed that cohort A patients with unfavorable baseline characteristics, including either PD-L1 negative tumors (n=13), elevated lactate dehydrogenase (LDH) levels (n=11), or M1c (n=17) obtained both favorable response rates and durable responses. The ORR was 61.5%, 79%, and 88% for patients with PD-L1 - tumors, elevated LDH, and M1c, respectively. The mPFS was 7.1 months for patients with PD-L1 - tumors, 30.9 months for patients with elevated LDH, and 27.9 months for M1c patients. Cohort B: At data cut-off, the best overall response was stable disease for 2 of the 10 evaluable patients. The mPFS was 2.4 months (95% CI 1.38 to 2.52), and the mOS was 16.7 months (95% CI 4.13 to NR). Conclusion This long-term follow-up confirms the promising and durable responses in cohort A. Subgroup analyses of patients with unfavorable baseline characteristics revealed that high response rates and survival rates were also found in patients with either PD-L1 negative tumors, elevated LDH levels, or M1c. No meaningful clinical effect was demonstrated in cohort B patients. Trial registration number NCT03047928.
AB - Background We have previously published initial efficacy of the indoleamine 2,3-dioxygenase (IDO)/anti-programmed death ligand 1 (PD-L1) vaccine in combination with nivolumab in 30 anti-PD-1 therapy naïve patients with metastatic melanoma (cohort A). We now report long-term follow-up of patients in cohort A. Further, we report results from cohort B, where the peptide vaccine was added to anti-PD-1 therapy for patients with progressive disease during anti-PD-1 treatment. Methods All patients were treated with a therapeutic peptide vaccine in Montanide targeting IDO and PD-L1 combined with nivolumab (NCT03047928). A long-term follow-up of safety, response rates, and survival rates were performed in cohort A including patient subgroup analyses. Safety and clinical responses were analyzed for cohort B. Results Cohort A: At data cut-off, January 5, 2023, the overall response rate (ORR) was 80%, and 50% of the 30 patients obtained a complete response (CR). The median progression-free survival (mPFS) was 25.5 months (95% CI 8.8 to 39), and median overall survival (mOS) was not reached (NR) (95% CI 36.4 to NR). The minimum follow-up time was 29.8 months, and the median follow-up was 45.3 months (IQR 34.8-59.2). A subgroup evaluation further revealed that cohort A patients with unfavorable baseline characteristics, including either PD-L1 negative tumors (n=13), elevated lactate dehydrogenase (LDH) levels (n=11), or M1c (n=17) obtained both favorable response rates and durable responses. The ORR was 61.5%, 79%, and 88% for patients with PD-L1 - tumors, elevated LDH, and M1c, respectively. The mPFS was 7.1 months for patients with PD-L1 - tumors, 30.9 months for patients with elevated LDH, and 27.9 months for M1c patients. Cohort B: At data cut-off, the best overall response was stable disease for 2 of the 10 evaluable patients. The mPFS was 2.4 months (95% CI 1.38 to 2.52), and the mOS was 16.7 months (95% CI 4.13 to NR). Conclusion This long-term follow-up confirms the promising and durable responses in cohort A. Subgroup analyses of patients with unfavorable baseline characteristics revealed that high response rates and survival rates were also found in patients with either PD-L1 negative tumors, elevated LDH levels, or M1c. No meaningful clinical effect was demonstrated in cohort B patients. Trial registration number NCT03047928.
KW - immunotherapy
KW - melanoma
KW - nivolumab
KW - vaccination
UR - http://www.scopus.com/inward/record.url?scp=85159836944&partnerID=8YFLogxK
U2 - 10.1136/jitc-2023-006755
DO - 10.1136/jitc-2023-006755
M3 - Journal article
C2 - 37217243
AN - SCOPUS:85159836944
VL - 11
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
SN - 2051-1426
IS - 5
M1 - e006755
ER -
ID: 370661659