Delving into the Latest Updates on Asudemotide with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide vaccine, Prophylactic vaccine

Synonyms

Target

Mechanism

DEPDC1 inhibitors(DEP domain containing 1 inhibitors), IGF2BP3 inhibitors(insulin like growth factor 2 mRNA binding protein 3 inhibitors), KIF20B inhibitors(kinesin family member 20B inhibitors)

+ [2]

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases+ [1]

Active Indication

Esophageal CarcinomaBladder CancerNon-Small Cell Lung Cancer

Inactive Indication-

Originator Organization

OncoTherapy Science, Inc.

Active Organization

OncoTherapy Science, Inc.

Shionogi & Co., Ltd.

Inactive Organization

Shionogi, Inc.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC58H80N10O17

InChIKeyFIURBSUJWCYXNV-OXOWVKQUSA-N

CAS Registry1018833-53-8

Gene Sequence

Sequence Code 72974

Source: *****

Exploratory study to determine S-588410-induced tumor infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients - Exploratory study to determine S-588410-induced tumor infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients

Start Date25 Jul 2016

Sponsor / Collaborator

Shionogi & Co., Ltd.

JPRN-UMIN000016954 / CompletedPhase 3

A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of S-588410 as adjuvant therapy after curative resection in patients with esophageal cancer - A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of S-588410 as adjuvant therapy after curative resection in patients with esophageal cancer

Start Date01 May 2015

Sponsor / Collaborator

Shionogi & Co., Ltd.

NCT02410369 / Unknown statusPhase 2

Phase II Study of S-588410 as Maintenance Monotherapy After Adjuvant Chemotherapy in Patients With Completely Resected Non-small- Cell Lung Cancer

In this clinical study, the investigators evaluate the efficacy and safety of S-588410 in patients who underwent an adjuvant chemotherapy after the complete resection of non-small-cell lung cancer.

Start Date01 Mar 2015

Sponsor / Collaborator

University of Tokyo

[+5]

100 Clinical Results associated with Asudemotide

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100 Translational Medicine associated with Asudemotide

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100 Patents (Medical) associated with Asudemotide

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3

Literatures (Medical) associated with Asudemotide

01 Oct 2024·Esophagus

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

Article

Author: Hikichi, Tetsuro ; Park, Jae-Hyun ; Yano, Masahiko ; Muro, Kei ; Kitagawa, Yuko ; Masaoka, Yasuhide ; Makino, Tomoki ; Miyata, Hiroshi ; Yasuda, Takushi ; Iguchi, Motofumi ; Igarashi, Kenji ; Hasegawa, Takahiro ; Doki, Yuichiro

AbstractBackgroundS-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC).MethodsThis phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming–Harrington class of weights.ResultsA total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity.ConclusionsS-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.

03 Jun 2022·Bladder Cancer

A Phase 2 Study of S-588410 Maintenance Monotherapy for Platinum-Treated Advanced or Metastatic Urothelial Carcinoma

Article

Author: Igarashi, Kenji ; Yamasaki, Toshinari ; Hussain, Syed A. ; Fujioka, Tomoaki ; Obara, Wataru ; Takashima, Satoru ; Ogawa, Osamu ; Iguchi, Motofumi ; Hasegawa, Takahiro ; Shimizu, Nobuaki

BACKGROUND: Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy. OBJECTIVE: To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A*24:02-restricted epitope peptides derived from five cancer-testis antigens (DEPDC1, MPHOSPH1, URLC10, CDCA1, and KOC1) in chemotherapy-treated, clinically stable patients with advanced or metastatic UC. MATERIALS AND METHODS: This open-label, international, phase 2 trial enrolled patients with UC who had completed≥4 cycles of first-line platinum-containing chemotherapy without disease progression. Forty-five HLA-A*24:02-positive patients received subcutaneous injections of S-588410 (Montanide ISA 51 VG with 1 mg/mL of each peptide) weekly for 12 weeks then once every 2 weeks thereafter for up to 24 months. Thirty-six HLA-A*24:02-negative patients did not receive S-588410 (observation group). The primary endpoint was the rate of cytotoxic T-lymphocyte (CTL) induction against≥1 of the peptides at 12 weeks. RESULTS: The CTL induction rate in the S-588410 group was 93.3% (p < 0.0001, one-sided binomial test with a rate of≤50% as the null hypothesis). The antitumor response rate was 8.9% in the S-588410 group and 0% in the observation group; median progression-free survival was 18.1 versus 12.5 weeks and median overall survival was 71.0 versus 99.0 weeks, respectively. The most frequent treatment-emergent adverse event was injection-site reactions (47 events, grades 1–3) reported in 93.3% (n = 42/45) of participants. CONCLUSIONS: S-588410 demonstrated a high CTL induction rate, acceptable safety profile, and modest clinical response, as maintenance therapy in participants with advanced or metastatic UC who had received first-line platinum-based chemotherapy (EudraCT 2013-005274-22).

01 Nov 2020·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Ide, N ; Hikichi, T ; Shirakawa, Y ; Nagira, M ; Puccio, I ; Marafioti, T ; Kato, K ; Nakagawa, T ; Daiko, H ; Furukawa, M ; Nakatsura, T ; Yoshimura, S ; Kojima, T ; Fujiwara, T ; Stoeber, K

AbstractCancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). 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.

100 Deals associated with Asudemotide

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Esophageal Carcinoma	Phase 3	-	OncoTherapy Science, Inc.	-
Bladder Cancer	Phase 2	-	Shionogi & Co., Ltd.	-
Bladder Cancer	Phase 2	-	OncoTherapy Science, Inc.	-
Non-Small Cell Lung Cancer	Phase 2	-	OncoTherapy Science, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EUCTR2013-005274-22-GB (ASCO_GU2021)	Phase 2	Metastatic urothelial carcinoma Maintenance	81	S-588410	reacrgdjkv(ywcdvijhxt) = dixllktdtf ccwhouomvo (jzhbhfulfe ) View more	-	02 Mar 2021
EUCTR2013-005274-22-GB (ASCO_GU2021)	Phase 2	Metastatic urothelial carcinoma Maintenance	81	S-588410 (Observation group)	(kkrpoulqpt) = nzynsbazhp tpecwcciyx (dbuxthcdco ) View more	-	02 Mar 2021
JPRN-UMIN000023324 (ESMO2018)	Phase 1	Esophageal Carcinoma	15	S-588410	dyhkweokan(qdhmiudlwo) = kfeliivjfo agxbdrraah (otwxegxfva ) View more	-	20 Oct 2018