Ivonescimab takes on pancreatic cancer

Akeso's ivonescimab, Exelixis's zanzalintinib and AstraZeneca's saruparib are each heading into pivotal studies in new cancer settings, the latest listings on the clinicaltrials.gov registry reveal.

Ivonescimab already has a huge expectations behind it, having been licensed to Summit for $500m up front, but its biggest focus at present rests on non-small cell lung cancer, where the coming year promises significant catalysts. The new pivotal effort, the Harmoni-GI2 study, takes it into pancreatic cancer, though it is Akeso-sponsored and will be conducted in China.

Akeso first mentioned plans to take ivonescimab into pancreatic cancer last August, and as yet there is no indication whether Summit will follow suit with a global pivotal trial. Harmoni-GI2 will test a chemo combo, with or without the anti-CD47 MAb ligufalimab, in front-line pancreatic ductal adenocarcinoma, measuring overall survival versus chemo alone as primary endpoint.

Me-better?

While ivonescimab is seen as one of the biopharma industry's highest-profile hopes – offering the possibility of huge reward but also carrying massive risk should it fail – zanzalintinib and saruparib can be seen as me-better R&D candidates.

However, definitive evidence demonstrating that they are actually better than Exelixis's Cabometyx and AstraZeneca's Lynparza respectively has so far been lacking. Cabometyx, the Exelixis blockbuster that comes off patent in 2030, has shown efficacy that on a cross-trial basis hasn't been beaten by zanzalintinib, a similarly acting next-generation asset.

The zanzalintinib data, from the colorectal cancer trial Stellar-001, caused investor pain when presented at ASCO-GI in January. At the same time Exelixis doubled down on the project, claiming its $5bn a year revenue potential and promising to start the Stellar-311 trial in neuroendocrine tumours; this is now live on clinicaltrials.gov, technically structured as a phase 2/3 study.

AstraZeneca's PARP inhibitor Lynparza, subject to a commercialisation agreement with Merck & Co, is like Cabometyx an established blockbuster, and looks to be facing patent expiry from around 2029. Saruparib is a PARP1-selective molecule designed to offer an improved safety profile – something that early data at last year's AACR meeting just about showed.

However, these findings came from a small trial, and also showed increased toxicity at higher dosing with no added efficacy benefit. Astra has moved saruparib into phase 3 development in breast and first-line prostate cancers, and its latest pivotal effort is the Evopar-Prostate02 study, in the adjuvant setting.

This will combine saruparib with androgen-deprivation therapy, and enrol patients with high-risk prostate cancer with BRCA1 or 2 mutation. Lynparza plus Zytiga is approved for BRCA-mutated prostate cancer, but this concerns the metastatic, castration-resistant setting.

Newly disclosed pivotal studies

Note: *ph2/3 study. Source: OncologyPipeline.