garetatug rezetecan (SHR-A1904) / Jiangsu Hengrui Pharma, EMD Serono - LARVOL DELTA

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

Antibody-drug conjugates targeting the cadherin, claudin and nectin families of adhesion molecules. (PubMed, Front Mol Med) - "Enfortumab vedotin is an NECTIN4-targeting antibody-drug conjugate that is approved for the treatment of urothelial cancer, whereas other ADCs or derivatives that target NECTIN4, such as bulumtatug fuvedotin, SHR-A2102 and zelenectide pevedotin, are being studied in randomized phase III clinical trials. In contrast, arcotatug tavatecan, garetatug rezetecan, sonesitatug vedotin and tecotabart vedotin are anti-CLDN18.2 ADCs in phase III clinical trials for the treatment of CLDN18.2-positive gastric or gastroesophageal junction adenocarcinomas, and raludotatug deruxtecan is an anti-CDH6 ADC in a phase II/III clinical trial for the treatment of platinum-resistant ovarian cancer. ADCs that target cell-cell adhesion molecules are a rapidly emerging class of cancer therapeutics, and bispecific ADCs and longitudinal companion diagnostics are emerging to further improve the clinical benefits of conventional ADCs."

Journal • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer • CDH17 • CDH6 • CLDN18 • CLDN6

A Trial of Adebrelimab Plus (SHR-A1811/SHR-A1904 With Chemotherapy) or SHR-8068 as Treatment for Gastric/GEJ Cancer (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting ➔ Recruiting

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

A Trial of Adebrelimab Plus (SHR-A1811/SHR-A1904 With Chemotherapy) or SHR-8068 as Treatment for Gastric/GEJ Cancer (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd.

New P2 trial • 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 | 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

The clinical study results of Hengrui Medicine's innovative CLDN18.2 ADC drug SHR-A1904 for the treatment of gastric cancer were published in Nature Medicine (Jiangsu Hengrui Press Release) - P1 | N=107 | NCT04877717 | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd. | "A total of 95 CLDN18.2-positive advanced GC/GEJC patients were included in the study....In the dose escalation phase, SHR-A1904 showed good tolerability. The study selected 6.0mg/kg and 8.0mg/kg Q3W to continue exploring in the PK expansion and efficacy expansion phases. In terms of safety, the safety of SHR-A1904 in 95 patients was generally controllable....Among the 74 evaluable patients, 1 patient achieved complete remission, 25 patients achieved partial remission, the objective response rate (ORR) was 35.1% (95% CI, 24.4–47.1), and the confirmed ORR was 23.0% (95% CI, 14.0–34.2). In the 6.0mg/kg and 8.0mg/kg dose groups, the confirmed ORRs were 26.7% (95% CI, 12.3–45.9) and 26.5% (95% CI, 12.9–44.4), respectively; the median duration of remission was not reached (95% CI, 4.2 months–not reached) and 8.1 months (95% CI, 3.9–not reached), respectively."

P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

The antibody-drug conjugate SHR-A1904 for targeting CLDN18.2 in advanced gastric or gastroesophageal junction cancer: a phase 1 trial. (PubMed, Nat Med) - P1 | "In conclusion, SHR-A1904 demonstrated a manageable safety profile and encouraging anti-tumor activity in patients with CLDN18.2-positive G/GEJ cancer, warranting further investigation. ClinicalTrials.gov identifier: NCT04877717 ."

Journal • P1 data • Esophageal Cancer • Febrile Neutropenia • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • CLDN18

Establishment of Precision Targeted Therapy Strategies for Advanced Gastric Cancer Based on Novel Molecular Subtyping (clinicaltrials.gov) - P2 | N=140 | Not yet recruiting | Sponsor: China Medical University, China

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

SHR-A1904-I-101: A Study of SHR-A1904 in Patients With Advanced Solid Cancer (clinicaltrials.gov) - P1 | N=107 | Active, not recruiting | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2023 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

SHR-A1904-302: SHR-A1904 Compared With Investigator's Choice of Therapy in Claudin18.2 Positive Patitens With Second-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P3 | N=524 | Recruiting | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

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

SHR-A1904 Compared With Investigator's Choice of Therapy in Claudin18.2 Positive Patitens With Second-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P3 | N=524 | Not yet recruiting | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

Metastases • New P3 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Dr Xu on the Preliminary Efficacy of SHR-A1904 in Gastric/GEJ Cancer (OncLive) - P1 | N=94 | NCT04877717 | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd. | "At a data cutoff date of March 18, 2024, efficacy-evaluable patients in the gastric/GEJ cancer cohort who received the agent at 6.0 mg/kg (n = 9) achieved an overall response rate (ORR) of 55.6% (95% CI, 21.2%-86.3%). The disease control rate (DCR) in this patient population was 88.9% (95% CI, 51.8%-99.7%). Among efficacy-evaluable patients who received the agent at 8.0 mg/kg (n = 30), the ORR was 36.7% (95% CI, 19.9%-56.1%), and the DCR was 86.7% (95% CI, 69.3%-96.2%). In the total population (n = 58), the ORR was 27.6% (95% CI, 16.7%-40.9%), and the DCR was 81.0% (95% CI, 68.6%-90.1%)."

P1 data • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

CLDN18.2 targeted antibody-drug conjugate (ADC), SHR-A1904, in patients (pts) with gastric/gastroesophageal junction cancer (GC/GEJC): A phase I study (ESMO 2024) - P1 | "SHR-A1904 showed a manageable safety profile and promising anti-tumor activity in pretreated pts with CLDN18.2+ GC/GEJC."

Clinical • P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18

Exploratory Platform Research on Precision Therapy of Advanced Pancreatic Cancer (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Fudan University

Metastases • New P2 trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

SHR-A1904-301: SHR-A1904 Combinations in CLDN18.2-Positive Advanced Solid Tumor (clinicaltrials.gov) - P1 | N=924 | Recruiting | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

Hengrui Pharmaceutical (600276.SH): HRS-4642 injection and other drugs received drug clinical trial approval notice [Google translation] (Investing.com) - "...Hengrui Pharmaceutical...announced that the company and its subsidiaries Shanghai Shengdi Pharmaceutical Co., Ltd., Shanghai Hengrui Pharmaceutical Co., Ltd., and Suzhou Shengdia Biopharmaceutical Co., Ltd. have received notification from the National Medical Products Administration (hereinafter referred to as the National Medical Products Administration). 'State Food and Drug Administration') approved and issued the 'Drug Clinical Trial Approval Notice' for HRS-4642 Injection, Adebrelimab Injection, SHR-A1904 for Injection, SHR-9839 for Injection and SHR-A1921 for Injection 》, clinical trials will be launched in the near future."

New trial • Oncology • Solid Tumor

SHR-A1904 Combinations in CLDN18.2-Positive Advanced Solid Tumor (clinicaltrials.gov) - P1 | N=924 | Not yet recruiting | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

Metastases • New P1 trial • Oncology • Solid Tumor

Hengrui Medicine and Merck reach cooperation to jointly promote innovative cancer treatments [Google translation] (Jiangsu Hengrui Press Release) - "Jiangsu Hengrui Pharmaceutical Co., Ltd...today announced that it has entered into an agreement with Merck & Co., a leading technology company headquartered in Darmstadt, Germany. The independently developed PARP1 inhibitor HRS-1167 reached an exclusive licensing agreement. This is the first time Hengrui Medicine has reached a strategic cooperation with a large multinational company in the world. The agreement also includes exclusive option rights for Hengrui’s independently developed Claudin-18.2 antibody drug conjugate (ADC) SHR-A1904....According to the terms of the agreement, Hengrui will receive an down payment of 160 million euros, technology transfer fees and exercise fees of up to 90 million euros, as well as R&D milestone payments and sales milestone payments. The total potential payments above could be as high as 1.4 billion euros. In addition, Merck will also pay Hengrui a sales commission of up to a double-digit percentage."

Licensing / partnership • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Merck KGaA, Darmstadt, Germany, Strengthens Oncology Pipeline Through Strategic Partnership with Hengrui for Next-Generation Selective PARP1 Inhibitor and Antibody-Drug Conjugate (Businesswire) - "Merck KGaA...announced a strategic collaboration with Jiangsu Hengrui Pharmaceuticals Co. Ltd. (Hengrui). The partnership includes an exclusive license worldwide (ex-China) to develop, manufacture and commercialize Hengrui’s next-generation potent and selective PARP1 (poly (ADP-ribose) polymerase 1) trapping inhibitor HRS-1167. The agreement also includes an option to an exclusive license worldwide (ex-China) to develop, manufacture and commercialize Hengrui’s Claudin-18.2 antibody-drug conjugate (ADC) SHR-A1904. In addition, Merck KGaA, Darmstadt, Germany, has the option to co-promote both assets in China....Under the terms of the agreement, Merck KGaA, Darmstadt, Germany, will provide Hengrui with an upfront payment of €160 million."

Licensing / partnership • Solid Tumor

A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF SHR-A1904 IN SUBJECTS WITH ADVANCED SOLID TUMORS (clinicaltrials.gov) - P1/2 | N=83 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Initiation date: Dec 2022 ➔ May 2022

Metastases • Trial initiation date • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18

A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF SHR-A1904 IN SUBJECTS WITH ADVANCED SOLID TUMORS (clinicaltrials.gov) - P1/2 | N=83 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Initiation date: Jun 2022 ➔ Sep 2022

Trial initiation date • Oncology • Solid Tumor

A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF SHR-A1904 IN SUBJECTS WITH ADVANCED SOLID TUMORS (clinicaltrials.gov) - P1/2 | N=83 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF SHR-A1904 IN SUBJECTS WITH ADVANCED SOLID TUMORS (clinicaltrials.gov) - P1/2 | N=83 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P1/2 trial • Oncology • Solid Tumor

A Study of SHR-A1904 in Patients With Advanced Solid Cancer (clinicaltrials.gov) - P1; N=94; Recruiting; Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Oncology • Solid Tumor