Keytruda leads in prostate cancer, but better response analysis is needed

Snippets

Yesterday’s publication of results from the Keynote-199 study in the Journal of Clinical Oncology will remind investors that prostate cancer is emerging as another tumour type amenable to checkpoint blockade. Keynote-199, a study of Merck & Co's Keytruda, segmented subjects by PD-L1 expression and bone metastasis, but remission rates were poor across the board. The few subjects who responded did so with unexpectedly long duration, a not atypical story in immunotherapy, and the best responses apparently came in those with DNA repair defects. It is interesting that of the immuno-oncology players only Merck has made a significant push into this cancer type, boasting in February of having started three pivotal Keytruda studies in various combinations, including with Parp inhibition (Esmo 2019 – A place for Parps in prostate cancer, September 30, 2019). However, only academic trials appear to focus specifically on prostate cancer driven by DNA repair defects. Bristol-Myers Squibb’s Opdivo trial Checkmate-7DX, somewhat analogous to Merck’s Keynote-921, and Roche’s Tecentriq study Imbassador-250 are the only other phase III tests under way. Other PD-(L)1-blocking agents are being studied in prostate cancer too, but these are largely investigator-sponsored efforts.

Selected immunotherapy studies in prostate cancer
Trial Setting & design Enrolment
Keytruda
Keynote-641* mCRPC, Xtandi combo, vs Xtandi 1,200
Keynote-921* 2L mCRPC, docetaxel combo, vs docetaxel 1,000
Keylynk-010* 3L mCRPC, Lynparza combo, vs Zytiga or Xtandi 780
Keynote-199 mCRPC 370
Keylynk-007 HRRm &/or HRD+ve, Lynparza combo 300
Perseus-1** ≥2L mCRPC with high mutational load or DNA repair defect 100
Keynote-365 mCRPC, various combos 400
Opdivo
Checkmate-7DX* Chemo-naive ≥2L mCRPC, docetaxel combo, vs docetaxel 984
Checkmate-650 mCRPC, Yervoy or Jevtana combo 618
Checkmate-9KD mCRPC, Rubraca, docetaxel or Xtandi combo 330
ImmunoProst** DNA repair defects 29
NCT04019964** dMMR 15
Tecentriq
Imbassador-250* 3L mCRPC, Xtandi combo, vs Xtandi 771
NCT03821246** Neoadjuvant, +/- Xtandi 51
Imfinzi
NCT03810105** HSPC, Lynparza combo 32
NCT02788773** mCRPC, +/- tremelimumab 52
Bavencio
Pick-NEPC** Neuroendocrine phenotype 18
mCRPC=metastatic, castration-resistant prostate cancer; HRRm=homologous recombination repair mutation; HRD=homologous recombination deficiency; dMMR=mismatch repair deficient; HSPC=hormone-sensitive prostate cancer; *phase III; **investigator-sponsored. Source: clinicaltrials.gov.

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