ESMO 2024 preview – presidential focus

At any scientific congress the presidential or plenary sessions are arguably the most prestigious to be selected for presentation, and here this year’s ESMO meeting has delivered at least two surprises.

The first is the Pod1um-303 study of Zynyz, the under-the-radar anti-PD-1 MAb from Incyte, in an indication where it was first rejected by the FDA in 2021. The second is Amgen’s PRMT5 inhibitor AMG 193, which disappointed last year, and which has been promoted from a standard oral to ESMO’s presidential session. Late-breaking ESMO presidential abstracts also include Lenvima’s Leap-012 and Imfinzi’s Niagara trials.

The case of Zynyz is especially surprising. Last year this drug received its first approval, becoming the eighth anti-PD-(L)1 MAb to reach the US market. So low key was this that Incyte never even announced that it had submitted this accelerated approval filing, for second-line Merkel cell carcinoma.

Two years earlier the FDA had issued Incyte’s first shot at approval a complete response letter, following an adcom vote against the phase 2 Pod1um-202 trial in second-line squamous cell carcinoma of the anal canal (SCAC). This now comes back into focus as it’s the phase 3 Pod1um-303, of a Zynyz/chemo combo in first-line SCAC, that’s scored a late-breaking ESMO presidential slot.

Nothing is known about the data – ESMO late-breaking titles were published this week, but no further details are available for either late-breakers or regular abstracts – but Incyte says Pod1um-303 will support a Zynyz supplemental US filing by the year end.

PRMT5 upgrade

Meanwhile, the PRMT5 inhibitor AMG 193 was already known to have been accepted for an ESMO presentation, but this has just been moved from a standard oral session on 13 September to the last of three ESMO presidentials, on 16 September.

This upgrade will spur hopes that the data have improved since the first cut underwhelmed at last year’s Triple meeting. The PRMT5 mechanism is of importance to Tango Therapeutics, which has two such molecules in its pipeline, and Pathos AI, which last week licensed PRT811, a molecule discontinued by Prelude two years ago. Bristol Myers Squibb is developing the Mirati-originated MRTX1719.

Two other presidential presentations, both late-breaking, are also of note. Nothing is known about the outcome of Merck & Co’s Leap-012 trial of Lenvima plus Keytruda combined with transarterial chemoembolisation in non-metastatic liver cancer, but it’s notable that virtually all other Lenvima/Keytruda combo studies have failed.

Leap-012’s inclusion in ESMO’s Saturday presidential session will raise hopes that this trial will become only the third phase 3 study of this combo to score a win, after the registrational Keynote-581 and 775 trials, in front-line kidney and endometrial cancers respectively.

Finally, two months ago AstraZeneca toplined the Niagara study of Imfinzi, in adjuvant bladder cancer, as a success on EFS as well as OS. Full data will feature in a late-breaker at ESMO’s presidential session on Sunday.

While the results might be positive overall, some doubt remains about their ability to back US approval; Niagara included a chemo combo neoadjuvant in addition to an Imfinzi monotherapy adjuvant stage, and an FDA adcom recently called out trials in perioperative settings that don’t specifically split out the two different settings’ respective effects.

Selected ESMO 2024 presidential presentations

Source: ESMO.

This story has been updated. ESMO will take place in Barcelona, Spain, on 13-17 September 2024.