zeprumetostat (SHR-2554) / Jiangsu Hengrui Pharma, Treeline Biosci - LARVOL DELTA

A Study of SHR3680, HS-20093 and SHR2554 in Subjects With Prostate Cancer (clinicaltrials.gov) - P2 | N=218 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Treeline Announces First Clinical Trials and Secures $200M in Additional Funding (Businesswire) - "Treeline Biosciences (or Treeline) today announced the initiation of Phase 1 trials for two internally discovered programs, TLN-121 and TLN-372, and a third in-licensed program, TLN-254."

Financing • Trial status • Lymphoma • Solid Tumor

Phase II Clinical Study of SHR2554 Tablets Combined With Other Anti-tumor Treatments in Non-small Cell Lung Cancer Subjects (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of HRS-5041 Tablets Combined With Antitumor Therapy in Subjects With Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Trial completion date: Dec 2026 ➔ Jun 2027 | Trial primary completion date: Sep 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Multicenter, Open-Label Phase II Clinical Study Evaluating the Safety, Tolerability, and Efficacy of SHR2554 Tablets in Combination with Other Antitumor Therapies in Patients with Locally Advanced Unresectable or Metastatic Gastric or Gastro-oesophageal Junction Adenocarcinoma (ChiCTR) - P2 | N=366 | Recruiting | Sponsor: Harbin Medical University Cancer Hospital; Harbin Medical University Cancer Hospital

New P2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • HER-2 • PD-L1

Phase II Clinical Study of SHR2554 Tablets Combined With Other Anti-tumor Treatments in Non-small Cell Lung Cancer Subjects (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety and Efficacy of SHR2554 Combined With Other Antitumor Therapies in Gastric or Gastro-oesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=351 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Safety and Efficacy of SHR2554 Combined With Other Antitumor Therapies in Gastric or Gastro-oesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=351 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Jiangsu Hengrui Pharmaceuticals Co., Ltd. Announcement in Relation to the Approval for Drug Registration (HKEXnews) - "The NMPA conditionally approves the Company’s self-developed Class 1 innovative drug, Zeprumetostat Tablets (SHR2554 Tablets), for marketing. The drug is indicated for adult patients with relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) who have received at least one prior line of systemic therapy."

China approval • Peripheral T-cell Lymphoma

SHR2554 Combined With Endocrine Therapy in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Henan Cancer Hospital

New P2 trial • Breast Cancer • Oncology • Solid Tumor

EZH2 inhibitor SHR2554 enhances the anti-tumor efficacy of HDAC inhibitor Chidamide through STAT1 in T-cell lymphoma. (PubMed, Cell Death Dis) - "We inferred that STAT1 was the key driver of the synergistic effect using RNA-seq and ChIP-seq analysis. Our findings provide sufficient preclinical evidence in support of a potential combination therapy strategy for TCL patients."

Journal • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • STAT1

Inhibition of EZH2 by SHR2554 modifies subset ratios and suppresses polyfunctional responses of peripheral blood T cells from hematopoietic stem cell donors. (PubMed, Int Immunopharmacol) - "SHR2554 significantly attenuated CD107a expression and IFNγ/TNFα secretion from CD3+/CD4+/CD8+ T cells, thereby suppressing polyfunctional responses across T cell subsets SHR2554, a potent and highly selective small-molecule inhibitor of EZH2, demonstrated a remarkable anti-proliferative effect on donor peripheral blood T cells, and modified T cell ratios and suppressed their polyfunctional responses. SHR2554 therefore has potential for treating graft-versus-host disease."

Journal • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD4 • CD8 • IFNG • LAMP1 • TNFA

2025 EHA Oral | Hengrui's innovative drug EZH2 inhibitor SHR2554 announced key study results in relapsed/refractory peripheral T-cell lymphoma [Google translation] (Jiangsu Hengrui Press Release) - P1 | N=272 | NCT03603951 | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | "A total of 67 patients were enrolled in the study and treated with SHR2554....As of December 20, 2024, with a median follow-up of 15.2 months, 22 patients (32.8%) achieved complete remission, 21 patients (31.3%) achieved partial remission, and the IRC-assessed ORR was 64.2% (95% CI, 51.5-75.5). Benefits were observed in all subtypes (ORR: AITL, 70.3% [26/37]; PTCL-NOS, 57.1% [8/14]; ENKTL-NT, 50.0% [2/4]; ALCL, ALK-, 42.9% [3/7]; ALCL, ALK+, 50.0% [1/2]; MEITL, 100% [1/1]; others, 100% [2/2]). Among patients who responded, 51.2% (22/43) are still in response, and the estimated median DoR is 18.7 months (95% CI, 6.3-not reached [NR]). The median PFS is 10.0 months (95% CI, 3.7-15.7), and the median OS has not yet been reached."

P1 data • Anaplastic Large Cell Lymphoma • Angioimmunoblastic T-cell Lymphoma • Extranodal Natural Killer/T-cell Lymphoma • Monomorphic Epitheliotropic Intestinal T-cell Lymphoma • Peripheral T-cell Lymphoma

A PIVOTAL STUDY OF SHR2554, AN ORAL INHIBITOR AGAINST ENHANCER OF ZESTE HOMOLOG 2 (EZH2), IN RELAPSED OR REFRACTORY (R/R) PERIPHERAL T-CELL LYMPHOMA (PTCL) (ICML 2025) - P1, P3 | "All pts had received chemotherapy; moreover, all had been treated with tucidinostat or brentuximab vedotin (tucidinostat, 59 [88.1%]; brentuximab vedotin, 21 [31.3%]; both, 13 [19.4%]). The pivotal study met its primary endpoint, demonstrating that SHR2554 is efficacious and has a manageable safety profile in pts with r/r PTCL. Our findings position SHR2554 as a new potential therapeutic option for this challenging-to-treat population. A randomized controlled phase 3 study comparing SHR2554 with standard therapy for r/r PTCL is currently underway (NCT06122389)."

Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • EZH2

T-CELL LYMPHOMA TREATMENT: THE CHINESE PERSPECTIVE (ICML 2025) - "Among the new drugs, the first in class JAK1 inhibitor Golidocitinib is particularly notable (ORR 44.3%, CRR 23.9%, mDOR 20.7 months). Additionally, some domestic drugs from China (such as EZH2i SHR2554, EZH1/2i HH2853, and PI3Ki linperlisib) have also demonstrated promising efficacy and safety profiles in clinical trials for relapsed/refractory PTCLs...In conclusion, continuous exploration of novel drugs and innovative treatment combinations remains pivotal for improving TCL treatment outcomes. It can be expected that after a long period of follow-up, the overall survival of PTCL patients in the current era will be effectively prolonged."

Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • EZH2

A PIVOTAL STUDY OF SHR2554, AN ORAL INHIBITOR AGAINST ENHANCER OF ZESTE HOMOLOG 2 (EZH2), IN RELAPSED OR REFRACTORY (R/R) PERIPHERAL T-CELL LYMPHOMA (PTCL) (EHA 2025) - P1, P3 | "All patients had received chemotherapy regimens; moreover, all patients had been treated with tucidinostat or brentuximab vedotin (tucidinostat, 59 [88.1%]; brentuximab vedotin, 21 [31.3%]; both, 13 [19.4%]). The pivotal study met its primary endpoint, demonstrating that SHR2554 is efficacious and has a manageable safety profile in patients with r/r PTCL. Our findings position SHR2554 as a new potential therapeutic option for this challenging-to-treat population. A randomized controlled phase 3 study comparing SHR2554 with standard therapy for r/r PTCL is currently underway (ClinicalTrials.gov, NCT06122389)."

Anemia • Hematological Disorders • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • EZH2

Pharmacokinetic interaction between SHR2554 and fluconazole: A single-center, open-label and one-sequence crossover phase I trial in healthy Chinese subjects. (PubMed, Eur J Pharm Sci) - "Safety evaluations indicated that the observed treatment-emergent adverse events were mild and transient. These findings underline the necessity of caution when co-administered SHR2554 with moderate CYP3A4 inhibitors in clinical settings, providing crucial insights for optimizing future clinical trials."

Journal • P1 data • PK/PD data • Hematological Disorders • Hematological Malignancies • Oncology

Safety profile of EZH2 inhibitors for cancer: a systematic review and meta-analysis. (PubMed, PeerJ) - "Specifically, for tazemetostat, the most common grade 3 or higher TRAE was neutropenia (5%). For SHR2554, the most prevalent grade 3 or higher TRAEs were thrombocytopenia (17%), neutropenia (8%), and anemia (7%)...EZH2 inhibitors demonstrate a manageable safety profile with a low incidence of severe TRAEs, emphasizing their potential as safe therapeutic options in cancer treatment. The low rate of severe TRAEs and the rare occurrences of treatment-related deaths support the continued clinical use and further investigation of EZH2 inhibitors."

Clinical • Journal • Retrospective data • Review • Hematological Disorders • Neutropenia • Oncology • Thrombocytopenia

…blockbuster new drugs expected to be approved for marketing in China in 2025 [Google translation] (Sohu.com) - "Hengrui Medicine's SHR2554: This is an EZH2 inhibitor used to treat relapsed or refractory peripheral T-cell lymphoma that has received at least one line of systemic treatment. The drug's marketing application has been accepted by the CDE and is expected to be approved in 2025."

China approval • Peripheral T-cell Lymphoma

Linperlisib Combined With EZH2 Inhibitor in Relapsed/Refractory Peripheral T-cell Lymphoma (PTCL) (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Combination therapy • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

SHR-1701 Combined with SHR2554 and BP102 for MCRC (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Fudan University

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

A Phase 1 Study of SHR2554 in Subjects With Relapsed or Refractory Mature Lymphoid Neoplasms (clinicaltrials.gov) - P1 | N=272 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2023 ➔ Aug 2026 | Trial primary completion date: Feb 2023 ➔ Feb 2026

Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Peripheral T-cell Lymphoma • BCL2 • BCL6 • EZH2

A Study of HRS-5041 Tablets Combined With Antitumor Therapy in Subjects With Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Hengrui Medicine: HRS-1167 tablets, HRS-5041 tablets and SHR2554 tablets received drug clinical trial approval notice [Google translation] (Wallstreet.org) - "Hengrui Medicine announced that the company and its subsidiary Chengdu Shengdi Pharmaceutical Co., Ltd. recently received the 'Drug Clinical Trial Approval Notice' for HRS-1167 tablets, HRS-5041 tablets and SHR2554 tablets approved and issued by the National Medical Products Administration, and will conduct clinical trials in the near future. HRS-5041 tablets will be combined with HRS-1167 tablets, SHR2554 tablets, abiraterone acetate tablets (II) and docetaxel for clinical trials of advanced prostate cancer."

New trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of HRS-5041 Tablets Combined With Antitumor Therapy in Subjects With Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=100 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Metastases • New P1/2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor