ESMO 2023 preview – Pluvicto splashes down among the late-breakers

An ESMO presidential session on 23 October that contains several key lung cancer readouts will also feature the PSMAfore study of Novartis’s Pluvicto, ESMO unexpectedly confirmed this week.

The data, in pre-chemo castration-resistant metastatic prostate cancer, are one the year’s most important oncology readouts, not only for Novartis but also for Point Biopharma, whose readout from the corresponding Splash trial is due in the fourth quarter. ApexOnco has detailed ESMO’s lung cancer late-breakers separately, but away from NSCLC the congress offers plenty of interest too.

PSMAfore, for instance, is said to be positive for radiographic PFS, but nothing is known yet about how clinically meaningful this is. The data could expand Pluvicto use beyond its approved post-chemo setting, though Novartis’s ability to supply the drug in the face of manufacturing problems that have taken months to rectify looms large.

Recently toplined

Datasets that have been toplined positive more recently, and now known to have been selected for presentation in full as ESMO late-breakers, include the InnovaTV-301 trial of Seagen’s anti-tissue factor ADC Tivdak, and the Litespark-005 study of Merck & Co’s HIF-2α inhibitor Welireg.

InnovaTV-301, said earlier this month to back Tivdak’s overall survival benefit versus chemo in second/third-line cervical cancer, could convert that drug’s accelerated US approval into a formal green light. Merck & Co’s Keytruda has a US combo label in first-line PD-L1≥1% cervical cancer, and the Keynote-A18 trial combining it with external beam radiotherapy, being presented at ESMO, could expand approval to all-comers, subject to a 23 January PDUFA decision.

Meanwhile, Litespark-005 could broaden Welireg’s approved use from the niche of Von Hippel-Lindau disease-associated to second/third-line renal cancer. Merck needs a broader label to justify paying $1bn for Welireg’s maker, Peloton, and while Litespark-005 has been toplined positive for PFS the absence so far of an OS benefit could be the subject of some discussion.

Selected ESMO late-breakers beyond lung cancer

Elsewhere, the mRNA rivals Moderna and BioNTech will face off with late-breakers on the personalised neoantigen immunotherapy mRNA-4157, and the anti-Claudin6 Car-T project BNT211 combined with a Claudin6-encoding immunotherapeutic called CARVac, respectively.

And several KRAS players have late-breakers, with Mirati’s Krazati plus Keytruda in first-line NSCLC facing off against Amgen’s Codebreak-300 trial of Lumakras plus Vectibix in KRAS G12C-positive colorectal cancer. Notably, Vectibix’s label advises against use in KRAS-mutated colorectal cancer; Mirati is expected to complete a Krazati filing for third-line colorectal cancer this year.

Also intriguing are first-in-human data for Jiangsu Hengrui’s HRS-4642, an inhibitor of KRAS G12D, not to mention Revolution Medicines’ RAS(on) inhibitor RMC-6236, claimed to hit many RAS variants, and already known to feature among ESMO’s standard presentations.

Finally, as ESMO continues highlighting trials that did not yield entirely positive data, Bristol’s Checkmate-901 trial of Opdivo plus chemo in first-line urothelial carcinoma has a presidential session slot. Checkmate-901’s Opdivo plus chemo arm was toplined positive for OS and PFS in July, after its Opdivo plus Yervoy cohort failed last year.

The ESMO congress takes place in Madrid, Spain on 20-24 October. Full late-breaker texts will be published on 18 October.