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
| Drug | Company | SC formulation | Clinical trial(s) | Status |
|---|---|---|---|---|
| Tecentriq | Roche | With Halozyme's Enhanze rHyPH20 (hyaluronidase) | Imscin-001 (ph3), in 2L NSCLC | Approved in GB & EU; US approval expected 2024 (15 Sep 2023 PDUFA date was missed owing to manufacturing problems) |
| Opdivo | Bristol Myers Squibb | With Halozyme's Enhanze rHyPH20 (hyaluronidase) | Studies in adjuvant melanoma & others, using autoinjector | Terminated |
| Checkmate-8KX (ph1/2) +/- hyaluronidase in solid tumours | Data showed flat 1.2g dose as optimal for ph3 | |||
| Checkmate-67T (ph3) using syringe & vial, in 2L renal cancer | Pharmacokinetic, ORR & PFS data at ASCO-GU 2024 | |||
| Keytruda | Merck & Co | No hyaluronidase | Keynote-555 cohort A (3wk cycle), ph1 in melanoma | Pharmacokinetic data at ASCO 2021 |
| Keynote-A86 (3wk cycle), ph3 chemo combo in 1L NSCLC | Toplined 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 NSCLC | Ends Sep 2024 | ||
| Keynote-C18 (6wk cycle), ph1 in solid tumours | Ends Sep 2026 | |||
| Imfinzi | Astrazeneca | Unclear | Scope-D1 (ph1), chemo combo in NSCLC & SCLC | Completed Sep 2023; data expected H2 2024 |
| Sasanlimab | Pfizer | No additional modification | Crest (ph3) in non-muscle invasive bladder cancer | Ends Jun 2024 |
Source: OncologyPipeline, ASCO & company statements.
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