SystImmune starts another first-line phase 3

SystImmune will soon have 11 Chinese phase 3 trials ongoing with its Bristol Myers Squibb-partnered anti-HER3 x EGFR antibody-drug conjugate izalontamab brengitecan. The latest, recently listed on clinicaltrials.gov, will test a combination with BeOne’s PD-1 inhibitor Tevimbra in first-line extensive-stage small-cell lung cancer.

The new study, slated to start this month and known as BL-B01D1-314, will add to an existing SystImmune-sponsored pivotal trial in second-line SCLC, BL-B01D1-304, which is set to complete this summer.

Bristol, which licensed iza-bren for $800m up front in December 2023, doesn’t have any global phase 3s under way in SCLC – yet. So far, the big pharma has begun three pivotal trials of iza-bren: Izabright-Lung01 in second-line EGFRm NSCLC; Izabright-Bladder01 in post-PD-(L)1 bladder cancer; and Izabright-Breast01 in first-line, PD-(L)1-ineligible triple-negative breast cancer.

While Bristol started its trials last year, iza-bren could be nearing the finish line in China. SystImmune has already filed the project there for second-line nasopharyngeal and oesophageal cancers. And in February the partners also announced positive topline results from a Chinese trial in second-line TNBC, BL-B01D1-307, suggesting that another filing there could be in the works.

However, one reason for caution could be toxicity, after a high rate of grade 3/4 neutropenia was seen in a US study presented at ESMO.

Competition

There are several rival HER3 x EGFR ADCs in the clinic, the most notable probably being BioNTech’s BNT3212, which came via that group's purchase of Biotheus, and went into phase 1/2 in the latter half of last year. That study is testing BNT3212 alone or in combination with the company’s PD-L1 x VEGF bispecific pumitamig in various solid tumours.

Meanwhile, Junshi’s similarly acting JS212 is in a Chinese phase 2 trial that encompasses both ES-SCLC and NSCLC. Other HER3 x EGFR ADC players include Avenzo (AVZO-1418, licensed from DualityBio), Huadong Medicine (HDM2024) and Innovent (IBI3005).

Meanwhile, the lead HER3-directed ADC is Merck & Co/Daiichi’s patritumab deruxtecan. However, that asset isn’t in development in SCLC, according to OncologyPipeline, and the partners withdrew a US filing in second-line EGFRm NSCLC after the Herthena-Lung02 trial failed on overall survival. The main focus for that project now appears to be breast cancer.

BioNTech and MediLink are also developing a HER3-targeting ADC, beruzatatug pelitecan, which recently went into phase 3 in China in second-line NSCLC and breast cancer. And Jiangsu HengRui’s ruzaltatug rezetecan is in pivotal Chinese trials in first and second-line NSCLC.

In SCLC the big recent development has been FDA approval of Amgen’s DLL3-targeting T-cell engager Imdelltra in relapsed disease; first-line trials are ongoing. However, the drug isn’t widely available outside the US.

With the latest study, Bristol and SystImmune could have a chance to steal a march on their HER3 rivals – but they have plenty of other irons in the fire.

SystImmune-sponsored phase 3 trials of iza-bren

Source: OncologyPipeline & clinicaltrials.gov.