Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab

Abstract

BackgroundWe 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.MethodsAll 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.ResultsCohort 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).ConclusionThis 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 numberNCT03047928.

Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression

“…PD-1 = programmed death 1. * Include pembrolizumab (20 patients), nivolumab (4 patients), or protocol (nivolumab + an IDO/PD-L1 peptide vaccine [ 19 ]) (1 patient). ** Include pembrolizumab (3 patients) or RELATIVITY-047 (LAG3 + nivolumab [ 20 ]) (1 patient).…”

Wilms’ tumor 1 -targeting cancer vaccine: Recent advancements and future perspectives

“…Phase I and II trials combining cancer peptide vaccines with ICIs show promising results. 48–50 These combinations include the human telomerase reverse transcriptase (hTERT) peptide vaccine and ipilimumab, 48 or indoleamine 2,3-dioxygenase (IDO)/programmed death ligand 1 (PD-L1)peptide vaccine and nivolumab for patients with advanced malignant melanoma, 49 or multi-peptide vaccine and nivolumab in adjuvant setting. 50 These combinations led to enhanced peptide-specific T cell responses, yielding excellent results with prolonged mPFS and mOS.…”

TGFβ-specific T cells induced by a TGFβ-derived immune modulatory vaccine both directly and indirectly modulate the phenotype of tumor-associated macrophages and fibroblasts

“… 5 The complete response rate was recently updated to 50%, demonstrating long-term responses to IMV. 6 …”

“…5 The complete response rate was recently updated to 50%, demonstrating long-term responses to IMV. 6 TGFβ is a potent immunosuppressive molecule and it is highly expressed in pancreatic cancer. 7 We developed an IMV with TGFβ1derived peptides formulated in Montanide ISA 51 (referred to as "TGFβ vaccine") that can control tumor growth in Pan02, a murine model of PDAC.…”