BioNTech's patritumab me-too advances

HER3-targeting antibody-drug conjugates came under scrutiny following the high-profile regulatory failure of patritumab deruxtecan from Merck & Co and Daiichi Sankyo, but developers, particularly in China, seem eager to continue development. 

The latest test comes from MediLink Therapeutics, which is advancing its BioNTech-partnered HER3-targeting ADC beruzatatug pelitecan into its first pivotal phase 3 trial. The move marks a significant milestone for the programme, which has spent time on clinical hold, raising an uncomfortable parallel with parti-dxd.

EGFRm lung cancer

The new study, recently posted on clinicaltrials.gov, is expected to begin in March, and will enrol 440 non-squamous non-small cell lung cancer patients who have progressed after at least one EGFR tyrosine kinase inhibitor. Progression free survival and overall survival will serve as dual primary endpoints in a head-to-head comparison against chemotherapy. 

Second-line EGFR-mutant NSCLC is the same setting that tripped up Merck/Daiichi's patri-dxd, whose Herthena-Lung02 study failed to demonstrate an overall survival benefit, and showed significant toxicities. A US filing ended up being withdrawn.

Meanwhile, beruza-P spent time in regulatory uncertainty, having been placed on US clinical hold after the FDA flagged risks of “illness and serious injury”. The hold did not last long, and it was lifted after the companies agreed to cap dosing at 3mg/kg. Notably, the dose to be tested in phase 3 is 2mg/kg, the new listing reveals.

So far, the companies have not reported NSCLC-specific data, but at ASCO in 2024 MediLink presented preliminary data that did include some lung cancer patients. These phase 1 results showed a 42% response rate across breast and lung cancer patients at doses below 3mg/kg. 

BioNTech, meanwhile, appears to be more interested in combination approaches. The company is studying the anti-HER3 ADC alongside other assets in its pipeline, for example pumitamig. A phase 1/2 in the same post-EGFR TKI NSCLC setting is expected to read out later this year. 

Bispecifics

Elsewhere, a bispecific HER3-targeting ADC approach appears to have shown better outcomes. 

Izalontamab brengitecan, an anti-EGFR x HER3 ADC from SystImmune and Bristol Myers Squibb, has produced encouraging results, at least in China. Three pivotal trials have reported positive readouts, including in triple-negative breast cancer in a trial that the companies just announced had met both co-primary endpoints. 

The other two studies, in head and neck and oesophageal cancers, are currently under regulatory review in China. Meanwhile, the companies have started global clinical trials, including one in NSCLC patients previously treated with EGFR inhibitors, whose readout is not expected until 2028. 

Phase 3 trials of HER3-targeting ADCs in 2nd-line EGFRm NSCLC

Notes: *also targets EGFR. Source: OncologyPipeline & clinicaltrials.gov.