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ASCO-GU – subcutaneous Opdivo puts the pressure on Merck

With Roche first over the regulatory line with a subcutaneous anti-PD-(L)1 – its formulation of Tecentriq got EU approval this month – the spotlight falls on the most significant player in this space, Merck & Co’s Keytruda. The pressure on Merck crept up a notch at the weekend’s ASCO Genitourinary Cancers Symposium as a third group, Bristol Myers Squibb, revealed stellar data from the Checkmate-67T trial of SC Opdivo. This yielded pharmacokinetics that Evercore ISI analysts described as “almost too good”, with average and trough 28-day serum concentrations up to twice as high for SC versus IV dosing, and a numerical response rate benefit (24% versus 18%) to boot. Bristol and Merck’s plans have changed here: Bristol abandoned an autoinjector in favour of a syringe and vial formulation, while Merck has reported promising data with a first-generation SC Keytruda, but then turned to MK-3475A, a co-formulation with Alteogen’s hyaluronidase technology. Data from the phase 3 Keynote-D77 study of the latter are expected some time this year. 2024 should also bring the first results on SC Imfinzi, from the phase 1 Scope-D1 study; that ended last September, and it’s not clear why AstraZeneca plans to sit on the data for a year.


Selected subcutaneous PD-(L)1 projects in the clinic

DrugCompanySC formulationClinical trial(s)Status
TecentriqRocheWith Halozyme's Enhanze rHyPH20 (hyaluronidase)Imscin-001 (ph3), in 2L NSCLCApproved in GB & EU; US approval expected 2024 (15 Sep 2023 PDUFA date was missed owing to manufacturing problems)
OpdivoBristol Myers SquibbWith Halozyme's Enhanze rHyPH20 (hyaluronidase)Studies in adjuvant melanoma & others, using autoinjectorTerminated
Checkmate-8KX (ph1/2) +/- hyaluronidase in solid tumoursData showed flat 1.2g dose as optimal for ph3
Checkmate-67T (ph3) using syringe & vial, in 2L renal cancerPharmacokinetic, ORR & PFS data at ASCO-GU 2024
KeytrudaMerck & CoNo hyaluronidaseKeynote-555 cohort A (3wk cycle), ph1 in melanomaPharmacokinetic data at ASCO 2021
Keynote-A86 (3wk cycle), ph3 chemo combo in 1L NSCLCToplined positive for pharmacokinetics, Aug 2023
Coded MK-3475A, co-formulation with Alteogen's MK-5180 (rh hyaluronidase)Keynote-D77 (6wk cycle), ph3 chemo combo in 1L NSCLCEnds Sep 2024
Keynote-C18 (6wk cycle), ph1 in solid tumoursEnds Sep 2026
ImfinziAstrazenecaUnclearScope-D1 (ph1), chemo combo in NSCLC & SCLCCompleted Sep 2023; data expected H2 2024
SasanlimabPfizerNo additional modificationCrest (ph3) in non-muscle invasive bladder cancerEnds Jun 2024

Source: OncologyPipeline, ASCO & company statements.


Molecular Drug Targets