Delving into the Latest Updates on HRS-4642 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

KRAS G12D

Action

inhibitors

Mechanism

KRAS G12D inhibitors(GTPase KRas G12D inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease

Active Indication

Pancreatic Ductal AdenocarcinomaKRAS G12D mutation Solid TumorsAdvanced Malignant Solid Neoplasm+ [1]

Inactive Indication-

Originator Organization

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Active Organization

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC34H35F3N6O3

InChIKeyXLWBILUNGOIIFR-OWBPVYLJSA-N

CAS Registry2836263-09-1

ⅠB期阶段主要研究目的：评估SHR-1826联合其他抗肿瘤治疗在晚期恶性实体瘤受试者中的安全性和耐受性，并确定II期临床研究推荐使用剂量（RP2D）。次要研究目的：评估SHR-1826联合其他抗肿瘤治疗的初步疗效、PK特征及免疫原性。 Ⅱ期阶段主要研究目的：基于客观缓解率（ORR），评价SHR-1826联合其他抗肿瘤治疗在晚期恶性实体瘤患者中的有效性。次要研究目的：基于其他有效性终点，评价SHR-1826联合其他抗肿瘤治疗在晚期恶性实体瘤的有效性；评价SHR-1826联合其他抗肿瘤治疗的安全性。

[Translation]

The main study objectives of the Phase IB stage are to evaluate the safety and tolerability of SHR-1826 combined with other anti-tumor therapies in subjects with advanced malignant solid tumors, and to determine the recommended dose (RP2D) for Phase II clinical studies. Secondary study objectives: To evaluate the preliminary efficacy, PK characteristics and immunogenicity of SHR-1826 combined with other anti-tumor therapies. The main study objectives of the Phase II stage are to evaluate the effectiveness of SHR-1826 combined with other anti-tumor therapies in patients with advanced malignant solid tumors based on the objective response rate (ORR). Secondary study objectives: Based on other efficacy endpoints, evaluate the effectiveness of SHR-1826 combined with other anti-tumor therapies in advanced malignant solid tumors; evaluate the safety of SHR-1826 combined with other anti-tumor therapies.

Start Date18 Feb 2025

Sponsor / Collaborator

Suzhou Suncadia Biopharmaceuticals Co., Ltd.

NCT06770452

/ Not yet recruitingPhase 2IIT

A Single-arm Phase II Study of HRS-4642 with Nimotuzumab and Chemotherapy for First-line Treatment of Advanced Pancreatic Cancer Patients with KRAS G12D Mutations

This study is a single-arm phase II clinical study to include 32 patients with advanced pancreatic cancer with KRAS G12D mutation to evaluate the effectiveness of HRS-4642 combined with nitutuzumab and AG for first-line treatment of advanced pancreatic cancer.

Start Date01 Feb 2025

Sponsor / Collaborator

Zhejiang University

ChiCTR2400094738

/ SuspendedPhase 1/2IIT

An exploratory study of HRS-4642 in combination with anti-tumor agents for the treatment of KRAS G12D mutant advanced colorectal cancer

Start Date06 Jan 2025

Sponsor / Collaborator

Fudan University Cancer Hospital

100 Clinical Results associated with HRS-4642

Login to view more data

100 Translational Medicine associated with HRS-4642

Login to view more data

100 Patents (Medical) associated with HRS-4642

Login to view more data

4

Literatures (Medical) associated with HRS-4642

01 Jul 2024·Cancer Cell

Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer

Article

Author: Jia, Keyi ; He, Feng ; Chen, Yingxue ; Yu, Yaxin ; Huang, Kan ; Mao, Shiqi ; Sun, Xing ; Ren, Shengxiang ; Wang, Zaiyong ; Mao, Rongfu ; Jiang, Tao ; Zhang, Zhe ; Yu, Jia ; Liu, Xinyu ; Shi, Wei ; Shao, Chuchu ; Cai, Xinlei ; Li, Xin ; Li, Wei ; Dai, Zican ; Luo, Libo ; Li, Chongyang ; Shen, Feng ; He, Ning ; Zhou, Caicun ; Zhang, Jun ; Wang, Wanying ; Li, Fei ; Li, Jiayu

KRAS G12D is the most frequently mutated oncogenic KRAS subtype in solid tumors and remains undruggable in clinical settings. Here, we developed a high affinity, selective, long-acting, and non-covalent KRAS G12D inhibitor, HRS-4642, with an affinity constant of 0.083 nM. HRS-4642 demonstrated robust efficacy against KRAS G12D-mutant cancers both in vitro and in vivo. Importantly, in a phase 1 clinical trial, HRS-4642 exhibited promising anti-tumor activity in the escalating dosing cohorts. Furthermore, the sensitization and resistance spectrum for HRS-4642 was deciphered through genome-wide CRISPR-Cas9 screening, which unveiled proteasome as a sensitization target. We further observed that the proteasome inhibitor, carfilzomib, improved the anti-tumor efficacy of HRS-4642. Additionally, HRS-4642, either as a single agent or in combination with carfilzomib, reshaped the tumor microenvironment toward an immune-permissive one. In summary, this study provides potential therapies for patients with KRAS G12D-mutant cancers, for whom effective treatments are currently lacking.

01 Jul 2024·Cancer Cell

HRS-4642: The next piece of the puzzle to keep KRAS in check

Article

Author: Drosten, Matthias ; Flores-Gómez, Alejandra A

KRAS^G12D is the most frequent KRAS mutation in human cancer. In this issue, Zhou et al. describe a novel KRAS^G12D inhibitor, HRS-4642, that shows potent and selective anti-tumor activity across various models and synergizes with proteasome inhibitors. Responses have also been observed in patients during an ongoing phase 1 trial.

12 Dec 2023·Cancer Discovery

Drugging RAS: Moving Beyond KRASG12C

Article

AbstractPreliminary results from phase I trials respectively evaluating RMC-6236, a pan-RAS inhibitor, and HRS-4642, a KRASG12D inhibitor, indicate that both are safe and show promising signs of antitumor activity. These are just two of the candidate RAS therapies in a burgeoning development space as the field looks ahead to drugs that hit more than just KRASG12C.

100 Deals associated with HRS-4642

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Ductal Adenocarcinoma	Phase 2	China	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	01 Oct 2024
KRAS G12D mutation Solid Tumors	Phase 2	China	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	05 Jul 2024
Advanced Malignant Solid Neoplasm	Phase 2	China	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	01 Jul 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	China	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	29 May 2024

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05533463 (ESMO 12023 \| ESMO 22023) Manual	Phase 1	KRAS G12D mutation Solid Tumors KRAS G12D	18	HRS-4642 (advanced solid tumors harboring KRAS G12D mutation)	(dprqqsehbm) = jabcdhipub cfedkedizw (schegsigxe ) View more	Positive	22 Oct 2023