SystImmune expands its iza-bren programme again

SystImmune will soon have 13 Chinese pivotal trials ongoing with its Bristol Myers Squibb-partnered ADC izalontamab brengitecan. The latest, recently revealed on clinicaltrials.gov and set to start this month, will test the anti-HER3 x EGFR project in second-line biliary tract cancer.

The study, known as BL-B01D1-317, will enrol patients who have progressed on a PD-(L)1 inhibitor and chemo, who will receive either iza-bren or chemo; the primary endpoint is overall survival. Meanwhile, two more Chinese phase 3s are set to feature at ASCO: BL-B01D1-305 and BL-B01D1-307, in second-line oesophageal squamous cell carcinoma and triple-negative breast cancer respectively.

BL-B01D1-305 supported a China filing in January, while the partners toplined a win in BL-B01D1-307. Iza-bren is also awaiting an approval decision in China for third-line nasopharyngeal carcinoma.

The next SystImmune-sponsored study to read out could be BL-B01D1-301, in second-line EGFR-mutant non-small cell lung cancer.

Global trials

All this could give clues about how iza-bren will fare in global trials. BL-B01D1-301 will be particularly relevant for Bristol, which is carrying out the analogous phase 2/3 Izabright-Lung01, also in patients progressed on an anti-EGFR TKI.

Bristol, which licensed iza-bren for $800m up front in December 2023, is also running Izabright-Bladder01 in post-PD-(L)1 bladder cancer; and Izabright-Breast01 in first-line, PD-(L)1-ineligible triple-negative breast cancer. The former is similar to SystImmune’s BL-B01D1-309.

However, results from the Bristol-sponsored studies are some way off. The most advanced, Izabright-Breast01, has a primary completion date of March 2026.

Bristol and SystImmune will be hoping that targeting EGFR, as well as HER3, could help them sidestep the problems that have hit Merck & Co/Daiichi Sankyo’s HER3-targeting ADC patritumab deruxtecan, whose US filing in second-line EGFRm NSCLC was withdrawn after the Herthena-Lung02 trial failed on overall survival.

HengRui HER3 win

However, Jiangsu HengRui just toplined a win with its own anti-HER3 ADC ruzaltatug rezetecan in the Chinese SHR-A2009-301 study in the same setting. The group said the trial met its primary PFS endpoint at an interim analysis, but didn’t disclose any data.

HengRui also has a first-line NSCLC trial, SHR-A2009-302. The analogous iza-bren trial is the SystImmune-sponsored BL-B01D1-308, with Bristol not yet venturing to the front line.

Meanwhile, the focus for patri-dxd now seems to be breast cancer.

OncologyPipeline lists over 20 clinical-stage anti-HER3 ADCs in development, including bispecifics. Other HER3 x EGFR projects include BioNTech’s BNT3212, Junshi’s JS212, Avenzo’s AVZO-1418 (licensed from DualityBio) and Innovent’s IBI3005.

SystImmune-sponsored phase 3 trials of iza-bren

Note: *phase 2/3, others are phase 3. Source: OncologyPipeline & clinicaltrials.gov.