Bristol goes pivotal with SystImmune-partnered conjugate

SystImmune’s antibody-drug conjugate izalontamab brengitecan is already in nine Chinese pivotal trials, and the group’s partner Bristol Myers Squibb will soon start the first global phase 3 of the project, which hits hits both EGFR and HER3.

Bristol has gone for first-line triple-negative breast cancer, specifically patients ineligible for checkpoint inhibitors plus chemo. This suggests that, even if successful, iza-can will be limited to patients with PD-L1 expression below 10%, as a Keytruda/chemo combo is approved in patients expression 10% or more.

That said, this would still represent a sizeable market, capturing around half of TNBC patients.

Izabright-Breast01

The Izabright-Breast01 trial, slated to start in July, will test iza-can versus chemo, with a primary endpoint of progression-free survival.

It adds to a Bristol-sponsored phase 1/2 Tagrisso/Keytruda combo trial in solid tumours, which began in February, and a SystImmune-funded but US-based phase 1 in NSCLC and other cancers, which started in August 2023, before Bristol licensed iza-can from for $800m up front in December 2023.

Bristol is on the hook for another $250m on the start of the latest trial, according to the most recent IPO document from Biokin, SystImmune’s parent company. Biokin doesn’t appear to have yet floated in Hong Kong, as planned.

Biokin is the holding company of Baili Pharmaceutical, which is sponsoring the aforementioned nine Chinese pivotal trials of iza-can, including one in second-line TNBC, and another in the bigger use of ER-positive/HER2-negative disease.

It will be interesting to see if Bristol moves into this more lucrative but more crowded space, or indeed any of the other indications that Baili/SystImmune is looking at, including lung, oesophageal and, most recently, bladder cancer.

Biokin’s IPO document notes that as well as a front-line trial in “a certain solid tumour” (presumably TNBC), Bristol is also planning a second-line study in another cancer in 2025. A second trial could trigger another $250m payment.

Other EGFR x HER3 ADC rivals include Avenzo Therapeutics, which recently licensed AVZO-1418 from DualityBio, and Junshi Biosciences, whose JS212 will soon go into phase 1/2 in China.

Izalontamab brengitecan phase 3 breast cancer trials

Note: all trials test iza-can monotherapy vs chemo. Source: OncologyPipeline & clinicaltrials.gov.