Gilead's Trop2 ADC Sacituzumab Govitecan Fails Phase 3 Trial in Metastatic Urothelial Cancer

May 31, 2024 09:39 CST Updated 09:39

Gilead Sciences

Antiviral Drug Developer

On May 30, Gilead Sciences, Inc. (NASDAQ: GILD) announcedTrop2 ADC TrodelvyPreliminary Results of the Phase 3 TROPiCS-04 Confirmatory Study for the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma (mUC),The study did not reachOverall Survival (OS)Primary Endpoint。

The trial failure was a blow to Gilead Sciences, as Trodelvy is the "cornerstone" of the company's cancer drug portfolio, with sales of the drug reaching $1.1 billion last year.This study aims to serve as the confirmatory trial for Trodelvy's accelerated approval in the United States for the treatment of locally advanced or metastatic urothelial cancer.Trial failure means FDA may revoke approval.

Sacituzumab Govitecan (Trodelvy®) is a Trop-2 targeted ADC drug developed by Immunomedics. In September 2020, Gilead Sciences announced the acquisition of Immunomedics for $21 billion, obtaining full ownership of Trodelvy.

Sacituzumab govitecan conjugates the humanized monoclonal antibody hRS7, which targets Trop-2 on the surface of cancer cells, with SN-38, the active metabolite of irinotecan, via a CL2A linker, forming a comprehensive, stable, and potent ADC-type anticancer drug. Unlike most ADCs that utilize ultratoxic drugs and stable linkers, IMMU-132 employs a moderately toxic drug with a moderately stable carbonate bond between SN-38 and the linker.

TROPiCS-04 Study（NCT04527991）It is an open-label, global, multicenter, randomized Phase 3 study evaluating Trodelvy versus single-agent chemotherapy (Treatment Physician's Choice, TPC) in patients with mUC who have previously received platinum-based chemotherapy and anti-PD-(L)1 therapy.

The study enrolled 711 patients, randomly assigned 1:1 to receive either Trodelvy or one of three TPC chemotherapy standard-of-care (SOC) regimens: paclitaxel, docetaxel, or vinflunine. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and duration of objective response (DoR), assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and blinded independent central review (BICR).

According to observations,TrodelvyOS was numerically improved, and there were also trends of improvement in certain pre-specified subgroups as well as in secondary endpoints such as progression-free survival (PFS) and overall response rate (ORR).

Compared with the chemotherapy control group,More Patients Treated with Trodelvy Died Due to Adverse Events, mainly related to complications such as infections caused by low white blood cell count.Gilead Sciences said it would investigate the data further but declined to answer questions about the death. The drug carries a boxed warning for "serious or life-threatening neutropenia," a condition caused by a lack of white blood cells.

In January, the Phase III EVOKE-01 study of Trodelvy versus docetaxel in previously treated patients with metastatic or advanced non-small cell lung cancer (NSCLC) also did not meet the primary endpoint of overall survival (OS).The consecutive failures of Trodelvy are not optimistic.

Summary

TROP2 is highly expressed in many solid tumors, such as breast cancer, lung cancer, colorectal cancer, ovarian cancer, cervical cancer, etc., and is one of the targets that pharmaceutical giants at home and abroad are competing to develop drugs for.Currently, the only Trop-2 ADC drug approved globally is Trodelvy from Gilead Sciences. Apart from this,The drugs with the most advanced progress are Dato-DXd from Daiichi Sankyo/AstraZeneca, which is under FDA review for marketing approval, and SKB264 from Kelun Biotech, which is under NMPA review for marketing approval. In China,Hengrui Medicine/Shengdiya Biotech, DualityBio, Shijian Bio/Lianning Bio, Fudan Zhangjiang Biomedical, Baili Pharmaceutical, Baikai Pharmaceutical, Minghui Pharmaceutical, Mabwell, Bio-Thera Solutions, etc., have all laid out TROP2 ADCs, all of which are in the early clinical stage.

Reference: Company official website

Scan the WeChat QR code to add the editor of the Antibody Circle.Those who meet the requirements can join the Antibody Circle WeChat group!

Please indicate: Name + Research Direction!

All articles reproduced in this official account are intended to convey more information, with the source and author clearly indicated. Media or individuals who do not wish to be reprinted may contact us (cbplib@163.com), and we will immediately proceed with deletion. All articles represent the views of the author and do not represent the position of this website.