S-531011 / Shionogi - LARVOL DELTA

Phase 2 Trial Of S-531011 With RadScopal In Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=30 ➔ 0 | Trial completion date: Jan 2031 ➔ Sep 2026 | Initiation date: Jan 2027 ➔ Aug 2026 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jan 2029 ➔ Sep 2026

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Colorectal Cancer • Oncology • Solid Tumor • MSI

Semi-Mechanistic Modeling of S-531011, a Humanized Anti-CCR8 Monoclonal Antibody, for Prediction of CCR8 Receptor Occupancy in Human Tumor Tissues. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The developed semi-mechanistic PK/RO model could predict human RO values of S-531011 in tumor tissues. Under typical model assumptions, simulations suggested the dose range of 80-800 mg of S-531011 every 3 weeks would achieve > 90% RO in tumor tissues."

Journal • Oncology • Solid Tumor • CCR8

Phase 2 Trial Of S-531011 With RadScopal In Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor • MSI

IGNITE-CRC: A Multicenter, Phase Ib/II Clinical Trial to Evaluate the Efficacy and Safety of Concurrent Combination Therapy of S-531011 Plus Fruquintinib or S-531011 Plus Fruquintinib Plus Pembrolizumab in Patients With MSS/pMMR Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=68 | Not yet recruiting | Sponsor: National Cancer Center Hospital East

New P1/2 trial • pMMR • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF

aCCeleR8-001: S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=282 | Recruiting | Sponsor: Shionogi | Trial completion date: Apr 2027 ➔ May 2028 | Trial primary completion date: Apr 2027 ➔ May 2028

Checkpoint inhibition • IO biomarker • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF • KRAS • NRAS

Preliminary results of a first-in-human phase 1b (aCCeleR8-001) study of S-531011, a humanized anti-CCR8 monoclonal antibody, in patients with advanced solid tumors. (ASCO 2025) - P1/2 | "S-531011 was well tolerated up to 1600 mg as monotherapy and in combination with pembrolizumab. A higher response rate in patients with CRC warrants further exploration of this tumor type in Phase 2 Dose Expansion part. Phase 2 CRC cohorts are currently ongoing."

Clinical • Metastases • P1 data • Colorectal Cancer • Oncology • Solid Tumor • CCR8

aCCeleR8-001: S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=274 | Recruiting | Sponsor: Shionogi | Phase classification: P1b/2 ➔ P1/2

Checkpoint inhibition • Combination therapy • Metastases • Monotherapy • Phase classification • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

S-531011, a novel anti-human CCR8 antibody, induces potent anti-tumor responses through depletion of tumor-infiltrating CCR8-expressing regulatory T cells. (PubMed, Mol Cancer Ther) - "S-531011 also depleted human tumor-infiltrating Tregs, but not Tregs derived from human peripheral blood mononuclear cells. These results suggest that S-531011 is a promising drug for inducing anti-tumor immunity without severe side effects in the clinical setting."

Journal • Oncology • CCR8

aCCeleR8-001: S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1b/2 | N=274 | Recruiting | Sponsor: Shionogi Inc. | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Combination therapy • Enrollment open • IO biomarker • Monotherapy • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

S-531011, a novel anti-human CCR8 antibody: Antibody screening and evaluation of biological profiles (SITC 2021) - "Conclusions We develop S-531011, a novel anti-human CCR8 humanized antibody which could selectively recognize and deplete tumor infiltrating Tregs. Based on our pre-clinical data, S-531011 has strong anti-tumor effect and we expect that it might be a potent novel tumor immuno-therapeutic agent with fewer side effect."

Oncology • CCR4 • CCR8

S-531011, a novel anti-human CCR8 antibody: anti-tumor responses through depletion of tumor-infiltrating CCR8-positive Tregs (SITC 2021) - "On the other hand, S-531011 didn’t reduce Tregs in human PBMC. Conclusions S-531011 is a promising drug which has a strong antitumor effect by depleting tumor-infiltrating CCR8+ Tregs, as a not only monotherapy but also combination therapy with other immune checkpoint inhibitors."

IO biomarker • Lung Cancer • Oncology • Solid Tumor • CCR8