Merck’s subQ Keytruda headscratcher
Awaiting the readout of a pivotal trial of subcutaneous Keytruda – a blockbuster lifecycle extension – why has Merck & Co just put this formulation into a new mid-stage study? The phase 2 Keynote-F65 trial is to start enrolling 60 lymphoma patients in mid-August, according to a recently posted clinicaltrials.gov entry. The answer, says Evercore ISI’s Umer Raffat, is that the pivotal Keynote-D77 lung cancer study can only support US approval across IV Keytruda’s current solid tumour indications, so a separate test is necessary for blood cancers, where Keytruda is approved for classical Hodgkin lymphoma. No such distinction is apparently necessary for EU approval. This addition comes against the backdrop of bigger changes in a space where Merck earlier abandoned plans for a SC formulation without hyaluronidase in favour of the current one, coded MK-3475A. Bristol has filed SC Opdivo with the FDA, and recently succeeded in having its PDUFA date brought forward from February 2025 to December 2024. Roche’s SC Tecentriq filing was knocked back, and after being resubmitted it now faces a 15 September action date. And AstraZeneca, which was already playing down the relevance of SC Imfinzi, has now terminated this project.
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; 15 Sep 2023 PDUFA date was missed owing to manufacturing problems; filing resubmitted, with new PDUFA date of 15 Sep 2024 |
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 | 29 Dec 2024 PDUFA date (brought forward from 28 Feb 2025) | |||
Keytruda | Merck & Co | No hyaluronidase | 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, to support US filing in solid tumour indications | ||
Keynote-F65 (6wk cycle), ph2 in Hodgkin lymphoma or large B-cell lymphoma | Starts Aug 2024, to support US filing in haematological cancer indications | |||
Sasanlimab | Pfizer | No additional modification | Crest (ph3) in non-muscle invasive bladder cancer | Ends Dec 2024 (delayed from Jun 2024) |
Imfinzi | AstraZeneca | Unclear | Scope-D1 (ph1), chemo combo in NSCLC & SCLC | Completed Sep 2023 with 18 of 124 patients enrolled; now terminated |
Source: OncologyPipeline.
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