Retlirafusp alfa Regulatory review Bispecific, Immunoconjugate

Antibody Information

Entry ID	1269
INN	Retlirafusp alfa
Status	Regulatory review
Drug code(s)	SHR-1701
Brand name	(Pending)
mAb sequence source	mAb human
General Molecular Category	Bispecific, Immunoconjugate
Format, general category	Full length Ab fusion
Format details	IgG-(TGFbeta-R2-ECD)2
Isotype (Fc)	IgG4
Light chain isotype	kappa
Linker	None
Ave. DAR	None
Conjugated/fused moiety	TGFbeta receptor II ECD
Discovery method/technology	None

Therapeutic information

Target(s)	PD-L1, TGF beta
Indications of clinical studies	Rectal cancer, cervical Cancer, Perioperative Treatment in Subjects With Locally Advanced Resectable Gastric Cancer or Gastroesophageal Junction Cancer, Small cell lung cancer, Pancreatic cancer, Non-small cell lung cancer, nasopharyngeal carcinoma, solid tumors
Primary therapeutic area	Cancer

Development stage information

Phase lengths*

*The graph represents early-stage clinical development phase lengths. For molecules approved or under evaluation for marketing authorization in the US is provided a complete overview of all clinical development phase lengths. Phase lengths are calculated from the start of the first in human (FIH) study (Start of clinical phase). “Start of Phase 2” bar represents Phase 1 length (Start of clinical phase to start of Phase 2); “Start of Phase 3” bar represents Phase 1+2 length (Start of clinical phase to start of Phase 3); “Date BLA/NDA submitted” bar represents Phase 1+2+3 length (Start of clinical phase to Date BLA/NDA submitted); and “Date of first US approval” bar represents Phase 1 to first US approval length (Start of clinical phase to Date of first US approval).

Most advanced stage of development (global)	Regulatory review China
Status	Active
Start of clinical phase (IND filing or first Phase 1)	November 15, 2018
Start of Phase 2
Start of Phase 3	June 22, 2021
Date BLA/NDA submitted to FDA
Year of first approval (global)	None
Date of first US approval
INN, US product name	None
US or EU approved indications	None

Company information

Company	Jiangsu HengRui Medicine Co. Ltd.
Licensee/Partner	Suzhou Suncadia Biopharmaceuticals Co. Ltd.
Comments about company or candidate	On September 19, 2024, the National Medical Products Administration (NMPA) accepted Hengrui Pharmaceutical's marketing authorization application for the Class 1 new drug Retlirafusp-α Injection (SHR-1701). The application seeks approval for its use in combination with Fluorouracil and platinum-based drugs for the first-line treatment of locally advanced unresectable, recurrent, or metastatic gastric and gastroesophageal junction adenocarcinoma. According to the pipeline on Suzhou Suncadia Biopharmaceuticals website and to clinicaltrials.gov there are 5 phase 2/3 or 3 studies: Phase 3 study for Cervical cancer (NCT05179239 recruiting as of March 29, 2022); Phase 2/3 study for Colorectal cancer (NCT04856787 recruiting as of July 13, 2021); Phase 3 study for Gastric or gastroesophageal junction cancer (NCT04950322 recruiting as of September 7, 2022); Phase 3 study for Non-small cell lung cancer (NCT05132413 not yet recruiting as of November 24, 2021); Phase 2/3 study for Perioperative treatment of resectable gastric or gastroesophageal junction cancer (NCT05149807 is enrolling by invitation as of February 10, 2022) NCT05179239 Phase 3 in cervical cancer started in Feb 2022. NCT04950322 Phase 3 in Gastric or Gastroesophageal Junction Cancer started in Dec 2021. NCT05149807 Phase 2/3 study in Gastric Cancer or Gastroesophageal Junction Cancer sponsored by Suzhou Suncadia Biopharmaceuticals Co., Ltd. started in Jan 2022. NCT04856787 Phase 2/3 study in CRC due to start in May 2021 sponsored by Suzhou Suncadia Biopharmaceuticals Co., Ltd. NCT04650633 A Phase II,Open-label Trial to Investigate the Efficacy and Safety of SHR-1701 in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck due to start in Jan 2021. NCT04580498 is a Phase 2 Trial of SHR-1701 With or Without Chemotherapy in Patients With Stage III NSCLC due to start Oct 15, 2020 NCT04679038 Phase 1/2 due to start in Jan 2021. NCT04624217 Phase 1/2 study in pancreatic cancer started in Nov 2020. NCT04324814 Phase 1 study in solid tumors recruiting as of March 2020. NCT04282070 Phase 1 in Nasopharyngeal Carcinoma not yet recruiting as of Feb 2020. NCT03710265 Phase I, Open-label Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of SHR-1701 in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected s due to start in Nov 2018 listed as not yet recruiting as of March 5, 2019
Full address of company	Lianyungang, Jiangsu Province, China. Asia China https://www.hengrui.com/en/about.html

Description/comment

Immune checkpoint target. S228P F234A L235A K447A mutations
SHR-1701 is an investigational bi-functional fusion protein composed of a mAb against PD-L1 fused to the extracellular domain of human TGF-β receptor II, designed to simultaneously block the two immunosuppressive signaling pathways commonly used by cancer cells. http://www.hrs.com.cn/hren/products_pipeline_oncology.html

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None