HengRui spreads its SERD

After last year beconing a new pivotal player in the oral SERD game, Jiangsu HengRui is now expanding its ambitions with its asset, HRS-8080. That’s according to clinicaltrials.gov, which has recently seen two new phase 3 trials for the project, in first-line and adjuvant breast cancer.

Both studies are in China, so HRS-8080 looks unlikely to challenge projects from western companies such as AstraZeneca, Lilly and Roche. But HengRui appears to be looking more broadly than local rivals including InventisBio and Jiangsu Simcere.

And HRS-8080 might be of interest to a US biopharma group keen to get into the SERD space on the back of any rival success in this field. Still, Arvinas and Pfizer haven’t found a partner for their asset, vepdegestrant, raising questions about partnering enthusiasm in this space.

HRS-8080 entered phase 3 last year with the HRS-8080-303 study in second-line breast cancer. This is the same setting in which Menarini’s Orserdu and Lilly’s Inluriyo have FDA approval; both drugs are limited to patients with ESR1 mutations.

Meanwhile, Roche appears to be gunning for an all-comers label for its contender giredestrant in second-line disease, and things should become clearer this year, with US and EU filings planned.

First line and adjuvant

In recent years, the focus has shifted to first-line and earlier disease, where it’s hoped that ESR1 mutation status will be less relevant, given that tumours are still ER-dependent.

In the front line HengRui will test HRS-8080 plus its CDK4/6 inhibitor dalpiciclib, versus Faslodex plus dalpiciclib, in patients with advanced or metastatic breast cancer who have developed resistance to adjuvant endocrine therapy. The primary endpoint is progression-free survival.

But that study, known as HRS-8080-301, isn’t slated to start until December 2026.

More immediate is HRS-8080-305, set to begin this month, in patients with high-risk early breast cancer who have previously received at least two years of standard adjuvant endocrine therapy. That trial will compare HRS-8080 against Femara or tamoxifen, with a primary endpoint of invasive breast cancer-free survival.

Western groups are also targeting first-line and perioperative settings, but HengRui’s main Chinese rivals, InventisBio and Simcere, have so far stuck to the second line.

InventisBio’s taragarestrant is going up against Faslodex in a phase 3 trial in patients who have received one to two prior lines of endocrine therapy, and this is to complete in November.

Meanwhile, Simcere’s Simrise study pits SIM0270 plus everolimus against investigator’s choice of Faslodex or everolimus plus exemestane, in patients previously given CDK4/6 inhibitors and endocrine therapy. Primary completion is August 2028; neither clinicaltrials.gov entry makes any mention of ESR1 mutation status.

The only project to prevail in what could be considered the front line so far is AstraZeneca’s camizestrant, but in an unusual setting: patients who develop an ESR1 mutation during first-line therapy with CDK4/6 and aromatase inhibitors, but before formal progression. An FDA approval decision is due this half.

In adjuvant disease Roche recently claimed a win with giredestrant, which if approved could go up against CDK4/6 inhibitors like Novartis’s Kisqali or Lilly’s Verzenio. Regulator filings are due this year.

Phase 3 trials of Jiangsu HengRui's HRS-8080 in breast cancer

Notes: *CDK4/6i; all studies being run in China; AI=aromatase inhibitor; IBCFS=invasive breast cancer-free survival. Source: OncologyPipeline & clinicaltrials.gov.