STA551 / Roche - LARVOL DELTA

Phase I study of STA551 (STA) a tumor-selective CD137 agonist, as monotherapy and in combination with atezolizumab (atezo) using CD8 PET imaging to assess pharmacodynamic effects (AACR 2026) - "STA demonstrated a manageable safety profile both as monotherapy and in combination with atezo. CD8 PET analysis suggested STA increased intratumoral CD8+ T cell levels in a subset of patients, with limited effects in normal organs. These findings potentially support the tumor-selective mechanism of action of STA as a CD137 agonist."

Combination therapy • Monotherapy • P1 data • PK/PD data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8

STA101JG: A Phase I study of STA551 and STA551 in combination with atezolizumab in patients with solid tumours (clinicaltrialsregister.eu) - P1 | N=30 | Active, not recruiting | Sponsor: Chugai Pharmaceutical Co. Ltd. | -> Active, not recruiting | Phase classification: PN/A ➔ P1

Enrollment closed • Phase classification • Oncology • Solid Tumor

Progress made in R&D activities during the period from January 1, 2025 to December 31, 2025 was as follows. (Chugai Press Release) - "We made a management decision to discontinue the in-house development of a RAS inhibitor LUNA18, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-CD137 agonistic switch antibody STA551, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-latent TGF-β1 monoclonal antibody SOF10, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-CLDN6/CD3/CD137 trispecific antibody SAIL66, considering obtained data up to date and the portfolio status."

Discontinued • Gastric Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Thoracic Cancer

Phase I first-in-human study of a novel anti-CD137 switch antibody agonist STA551 (STA) as monotherapy and in combination with atezolizumab (atezo) in patients (pts) with advanced solid tumors (ESMO 2025) - "Biomarker analysis suggested STA binding to T cells and CD137 signal activation at tumor sites. These findings potentially support tumor-selective activity of STA and wide therapeutic range."

Clinical • Combination therapy • First-in-human • IO biomarker • Metastases • Monotherapy • P1 data • Genito-urinary Cancer • Oncology • Penile Cancer • Solid Tumor • CD8 • TNFRSF9

In vivo validation of the switch antibody concept: SPECT/CT imaging of the anti-CD137 switch antibody Sta-MB shows high uptake in tumors but low uptake in normal organs in human CD137 knock-in mice. (PubMed, Transl Oncol) - "Ure-MB has a variable region mimicking the clinically available anti-CD137 agonist antibody urelumab, binding to CD137 regardless of ATP concentration. The present study provides evidence that the switch antibody concept works in vivo. Our findings encourage further clinical imaging studies to evaluate the biodistribution of STA551 in patients."

IO biomarker • Journal • Preclinical • Immune Modulation • Inflammation • Oncology

Single cell RNA sequencing revealed that the mechanism of the synergistic efficacy of STA551 and immune checkpoint inhibitor results from the induction of highly activated T cells in tumor (AACR 2022) - "The combination of STA551 and PD-L1 showed synergistic anti-tumor efficacy in a colon38-bearing human CD137 knock-in mouse model. Detailed mechanistic analysis showed that the combination of STA551 and PD-L1 induced highly activated CD8+T cells expressing chemokines and cytokines compared to monotherapy. This cluster also express chemokines, suggesting that other immune cells have been recruited."

Checkpoint inhibition • Clinical • IO biomarker • Colon Cancer • Oncology • CD8

In vivo imaging with two-photon microscopy to assess the tumor-selective binding of an anti-CD137 switch antibody. (PubMed, Sci Rep) - "In conclusion, we were able to assess switch antibody biodistribution in vivo through intravital imaging with two-photon microscopy. These results suggest that the tumor-selective binding of STA551 leads to a wide therapeutic window and potent antitumor efficacy without systemic immune activation."

IO biomarker • Journal • Preclinical • Oncology

Evaluation on tumor selectivity of immune response driven by STA551, an anti-CD137 agonist antibody activated in the presence of extracellular ATP (SITC 2021) - No abstract available

Oncology

[VIRTUAL] Responses of a novel tumor selective anti-CD137 agonist antibody activated by elevated extracellular ATP in tumor microenvironment (AACR 2021) - "Consistent with the binding profile, STA551 induced IFN-γ only in the presence of ATP, whereas urelumab induced IFN-γ regardless of ATP concentration in a human T cell assay. These results suggest that STA551, due to its tumor selective agonistic activity, has potent anti-tumor efficacy and a wide therapeutic window, providing a strongrationale for its clinical testing against a broad variety of cancers regardless of antigen expression, and for the further application of this novel platform to other targets in cancer therapy. STA551 is currently being tested in a phase 1 clinical study. We will here disclose the clinical study design for the first time."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • CD8 • IFNG

[VIRTUAL] Tumor selective immune responses of STA551, a novel anti-CD137 agonist antibody activated by extracellular ATP (SITC 2020) - "We also evaluated in vivo STA551’s effect on tumor growth, RNAseq-based immune-related gene expression, immunohistochemistry, and T cell activation in tumor and non-tumor tissues in human CD137 knock-in mice treated with mouse surrogate STA551 (Sta-MB) or urelumab (Ure-MB) in combination with anti-PD-L1 antibody. These results strongly support the clinical testing of STA551 for the treatment of solid tumors. STA551 is currently being tested in a phase 1 clinical study."

IO Biomarker • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • IFNG

[VIRTUAL] Tumor selective immune responses of STA551, a novel anti-CD137 agonist antibody activated by extracellular ATP (SITC 2020) - "We also evaluated in vivo STA551’s effect on tumor growth, RNAseq-based immune-related gene expression, immunohistochemistry, and T cell activation in tumor and non-tumor tissues in human CD137 knock-in mice treated with mouse surrogate STA551 (Sta-MB) or urelumab (Ure-MB) in combination with anti-PD-L1 antibody. These results strongly support the clinical testing of STA551 for the treatment of solid tumors. STA551 is currently being tested in a phase 1 clinical study."

IO Biomarker • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • IFNG

"Congrats and happy retirement @christa5551! 👏🏻" (@mday0423)

Non-Clinical Research Results of Chugai’s Switch Antibody STA551 Published in Cancer Discovery (Chugai Press Release) - "Chugai...announced that the results of non-clinical research on STA551, a Switch Antibody created by Chugai and currently in phase I clinical trial for solid tumors, have been published in Cancer Discovery Online...We are very much looking forward to the ongoing phase I clinical trial of STA551 to show a high safety profile and anti-tumor efficacy and become a drug that can contribute to the treatment of patients."

Preclinical • Oncology • Solid Tumor

Antibody to CD137 activated by extracellular adenosine triphosphate is tumor selective and broadly effective in vivo without systemic immune activation. (PubMed, Cancer Discov) - "STA551 was well tolerated even at 150 mg/kg/week in cynomolgus monkeys. These results provide a strong rationale for the clinical testing of STA551 against a broad variety of cancers regardless of antigen expression, and for the further application of this novel platform to other targets in cancer therapy."

IO Biomarker • Journal • Preclinical • Oncology • Solid Tumor

Chugai announces 2020 1st quarter results (Chugai Press Release) - "Chugai started phase I study for STA551 for the treatment of solid tumors....A phase II study started in Japan for the oncolytic type 5 adenovirus OBP-301(telomelysin), an oncolytic virus therapy from Oncolys BioPharma Inc., in esophageal cancer. For the engineered antibody AMY109 from Chugai research, the Company started a phase I study in solid tumors."

Trial status • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor