asudemotide (S-588410) / OncoTherapy, Shionogi - LARVOL DELTA

Announcement of publication of S-588410 Phase III clinical trial results for esophageal cancer patients [Google translation] (OncoTherapy Science Press Release) - P3 | N=276 | UMIN000016954 | Sponsor: Shionogi & Co., Ltd. | "We would like to inform you that a paper summarizing the results of the targeted phase III clinical trials has been published...A total of 276 ESCC patients received either S-588410 or a placebo (no peptide vaccine)....As a result, there was no significant difference in median RFS or median OS between the S-588410 group and the placebo group. It didn't work. CTL induction was confirmed within 12 weeks in 98.5% of the S-588410 group, with the highest expression The most common adverse event was injection site change (97.9%). Exploratory subpopulation analysis in the S-588410 group patients with upper thoracic ESCC, patients with grade 3 skin reactions at the injection site, or patients with highly induced CTLs. Prolonged survival was observed in patients who were guided."

P3 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Solid Tumor

A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma. (PubMed, Esophagus) - "S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development."

Clinical • Journal • P3 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Urothelial Cancer

[VIRTUAL] Phase II open-label study of S-588410 as maintenance monotherapy after first-line platinum-containing chemotherapy in patients with advanced or metastatic urothelial carcinoma. (ASCO-GU 2021) - P2 | "S-588410 showed a potent immune response and acceptable safety profile in patients with advanced or metastatic urothelial carcinoma, potentially offering a clinical benefit as post-chemotherapy maintenance therapy."

Clinical • Monotherapy • P2 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • DEPDC1

Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients. (PubMed, Cancer Immunol Immunother) - "In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324."

Biomarker • Clinical • IO Biomarker • Journal • Tumor microenvironment • Esophageal Cancer • Gastrointestinal Cancer • Oncology

Interim results from exploratory study to determine S-588410-induced tumor infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients. (ESMO 2018) - "The short-term treatment with S-588410 generated peptide-specific CTL and markedly increased CD8+ TIL density and PD-L1 expression on tumor tissue of esophageal cancer pts. These interim results suggest that the combination of S-588410 with anti-PD-1/PD-L1 antibody is expected to be more effective than monotherapy, particularly in pts with low TIL/PD-L1 status."

Biomarker • Clinical • IO Biomarker • PD(L)-1 Biomarker • Tumor microenvironment • Tumor-Infiltrating Lymphocyte • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Induction of tumour-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410 (ESMO 2019) - "Vaccination of S-588410 induces CD8+/ CD8+PD1+ tumor-infiltrating cells and PD-L1 expression in esophageal cancer. These results suggest that S-588410 enhances tumor immunity and PD1/PD-L1 axis. Thus a combination of S-588410 with anti-PD1/PD-L1 antibody is expected to be more effective than monotherapy."

IO Biomarker • PD(L)-1 Biomarker