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’ve 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 trial 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 who’ve progressed on an 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 and Daiichi’s HER3 ADC patritumab deruxtecan. The partners withdrew a US filing in second-line EGFRm NSCLC after the Herthena-Lung02 trial failed on overall survival.

HengRui HER3 win

However, Jiangsu HengRui just toplined a win with its similarly acting contender 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 HER3 ADCs, 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.