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

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

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

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) - No abstract available

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

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

Exploratory Clinical Study of SHR-0302 and SHR-2554 in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Fudan University | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Exploratory Clinical Study of SHR-0302 and SHR-2554 in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Fudan University

New P2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Efficacy and safety of SHR-2554 in advanced epithelioid sarcoma: A phase 2 trial. (ASCO 2024) - " To be eligible for inclusion, pts had to fulfill the following criteria: 8 years or older; histologically confirmed advanced or metastatic ES with loss of INI1 or upregulated mRNA level of EZH2; progressive disease after at least one line of doxorubicin-containing chemotherapy; the presence of measurable disease according to RECIST 1.1; an ECOG performance status of 0-1. SHR-2554 showed promising efficacy and an acceptable safety profile in pts with refractory ES, warranting further investigation."

Clinical • IO biomarker • Metastases • P2 data • Anemia • Hematological Disorders • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • SMARCB1

A Study of SHR2554 With Chemotherapy in Treatment-naïve Patients With Peripheral T-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

A Phase II Study of SHR2554 in Patients With Relapsed or Refractory Follicular Lymphoma (clinicaltrials.gov) - P2 | N=105 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P2 trial • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

A Study to Evaluate the Mass Balance of [14C]SHR2554 in Healthy Adult Volunteers (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Recruiting ➔ Completed

Trial completion • Hematological Malignancies • Lymphoma • Oncology

SHR2554 Clinical Study of Chidamide in the Treatment of T-cell Lymphoma (clinicaltrials.gov) - P3 | N=130 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Enhancer of zeste homolog 2 inhibitor SHR2554 in relapsed or refractory peripheral T-cell lymphoma: data from the first-in-human phase 1 study (Clin Cancer Res) - P1 | N=231 | NCT03603951 | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | "Totally, 28 patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). 18 (64%) patients had received ≥2 lines of previous anti-cancer therapies. The objective response rate was 61% (95% CI 41–78). Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI 7.4–not reached). Median progression-free survival was 11.1 months (95% CI 5.3–22.0), and 12-month overall survival rate was 92% (95% CI 72–98)."

P1 data • Peripheral T-cell Lymphoma

Enhancer of zeste homolog 2 inhibitor SHR2554 in relapsed or refractory peripheral T-cell lymphoma: data from the first-in-human phase 1 study. (PubMed, Clin Cancer Res) - "This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCLs."

Journal • P1 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Hengrui Medicine’s innovative drug EZH2 inhibitor SHR2554 has been approved for clinical use in combination with mature lymphocytic tumors [Google translation] (Jiangsu Hengrui Press Release) - "Recently, Hengrui Medicine received the 'Drug Clinical Trial Approval Notice' approved and issued by the National Medical Products Administration, agreeing to carry out SHR2554 tablets (specification 50 mg) combined with CHOP/CHOEP or CD20 monoclonal antibody-based treatment regimen for mature lymphocytes Clinical trials of tumors, specifically: an open, multi-center Phase Ib/II clinical study of SHR2554 combination therapy for mature lymphocytic tumors. Peripheral T Cell Lymphoma (PTCL) is a group of highly heterogeneous malignant proliferative diseases derived from mature T cells."

New P1/2 trial • Peripheral T-cell Lymphoma

A Study of SHR2554 With Chemotherapy in Treatment-naïve Patients With Peripheral T-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=100 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P1/2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Phase Ⅰ/Ⅱ Study of SHR2554 in Combination With SHR1701 in Patients With Advanced Solid Tumors and B-cell Lymphomas (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Chinese PLA General Hospital | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Mar 2023 ➔ Dec 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALK • BRAF • EGFR • ROS1

Effect of Omeprazole on Pharmacokinetics of SHR2554 in Healthy Subjects (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor

Effect of Omeprazole on Pharmacokinetics of SHR2554 in Healthy Subjects (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor