Prostate cancer is an indication so far untapped by checkpoint blockers, and for Bristol Myers Squibb it looks set to remain this way. In its second-quarter release today the company revealed the discontinuation of the phase 3 Checkmate-DX trial, which was testing Opdivo plus docetaxel/prednisone versus docetaxel/prednisone alone in metastatic castration-resistant prostate cancer patients who had progressed on a novel hormone therapy, effectively meaning Xtandi or Zytiga. The trial had a similar design to Merck & Co’s Keynote-921 study of Keytruda – and that failed a year ago. Bristol said Checkmate-7DX did not meet the primary endpoints of radiographic PFS at final analysis, or OS at an interim analysis, and its data-monitoring committee recommended that it be discontinued. For immunotherapy the one glimmer of hope in prostate cancer has come courtesy of Keynote-199, where the best responses apparently came in patients with DNA repair defects, according to the Journal of Clinical Oncology. However, even here efficacy was limited overall.Notable failures of anti-PD-(L)1 drugs in prostate cancerTrialProstate cancer settingDesignKeytruda (Merck & Co)Keynote-9212nd-line (post Xtandi/Zytiga) mCRPCDocetaxel combo, vs docetaxelKeylynk-0103rd-line (post Xtandi/Zytiga + chemo) mCRPCLynparza combo, vs Xtandi/ZytigaKeynote-9911st-line hormone-sensitiveXtandi + ADT combo, vs Xtandi + ADTKeynote-6411st-line (but allowed some prior Zytiga) mCRPCXtandi combo, vs XtandiOpdivo (Bristol Myers Squibb)Checkmate-7DX2nd-line (post Xtandi/Zytiga) mCRPCDocetaxel combo, vs docetaxelTecentriq (Roche)Imbassador-2503rd-line (post Zytiga + taxane) mCRPCXtandi combo, vs Xtandi
Prostate cancer is an indication so far untapped by checkpoint blockers, and for Bristol Myers Squibb it looks set to remain this way. In its second-quarter release today the company revealed the discontinuation of the phase 3 Checkmate-DX trial, which was testing Opdivo plus docetaxel/prednisone versus docetaxel/prednisone alone in metastatic castration-resistant prostate cancer patients who had progressed on a novel hormone therapy, effectively meaning Xtandi or Zytiga. The trial had a similar design to Merck & Co’s Keynote-921 study of Keytruda – and that failed a year ago. Bristol said Checkmate-7DX did not meet the primary endpoints of radiographic PFS at final analysis, or OS at an interim analysis, and its data-monitoring committee recommended that it be discontinued. For immunotherapy the one glimmer of hope in prostate cancer has come courtesy of Keynote-199, where the best responses apparently came in patients with DNA repair defects, according to the Journal of Clinical Oncology. However, even here efficacy was limited overall.
Notable failures of anti-PD-(L)1 drugs in prostate cancer
| Trial | Prostate cancer setting | Design |
|---|
| Keytruda (Merck & Co) |
| Keynote-921 | 2nd-line (post Xtandi/Zytiga) mCRPC | Docetaxel combo, vs docetaxel |
| Keylynk-010 | 3rd-line (post Xtandi/Zytiga + chemo) mCRPC | Lynparza combo, vs Xtandi/Zytiga |
| Keynote-991 | 1st-line hormone-sensitive | Xtandi + ADT combo, vs Xtandi + ADT |
| Keynote-641 | 1st-line (but allowed some prior Zytiga) mCRPC | Xtandi combo, vs Xtandi |
| Opdivo (Bristol Myers Squibb) |
| Checkmate-7DX | 2nd-line (post Xtandi/Zytiga) mCRPC | Docetaxel combo, vs docetaxel |
| Tecentriq (Roche) |
| Imbassador-250 | 3rd-line (post Zytiga + taxane) mCRPC | Xtandi combo, vs Xtandi |
