Merck finally gets under the skin with Keytruda
Merck is behind its checkpoint inhibitor rivals with subcutaneous Keytruda, but on Tuesday it took a step towards market with positive topline results from the Keynote-D77 trial, testing a chemo combo in first-line NSCLC. No detailed results are yet available; Merck only said that SC Keytruda showed noninferiority to the approved intravenous version on pharmacokinetic endpoints. The company plans to pesent the data at an upcoming conference and share them with regulatory authorities, although it didn’t give a timeline for this. The trial is expected to support all solid tumour indications. MK-3475A, the codename for SC Keytruda, is Merck’s second attempt here; it was previously developing a version without hyaluronidase. Roche is ahead with SC Tecentriq, which was approved by the FDA in September, while Bristol Myers Squibb is awaiting a US decision on SC Opdivo in December. Meanwhile Pfizer’s sasanlimab is expected to yield data in the first half of 2025, from the Crest trial, while AstraZeneca has fallen out of the running. Merck recently started the Keynote-F65 study of SC Keytruda in lymphoma, while the company also has Keynote-F84 in the works, testing SC versus IV Keytruda monotherapy in first-line NSCLC patients with high PD-L1 expression.
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 | FDA approved 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 (MK-3475A-D77; 6wk cycle), ph3 chemo combo in 1L NSCLC | Toplined positive Nov 2024; to support US filing in solid tumour indications | ||
| Keynote-F84 (MK-3475A-F84), China/Japan ph3 in NSCLC PD-L1 ≥50% | Not yet recruiting | |||
| Keynote-F65 (MK-3475A-F65; 6wk cycle), ph2 in Hodgkin lymphoma or large B-cell lymphoma | Started Oct 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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