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Lilly’s Verzenio, and CDK4/6 inhibition, hits a dead end in prostate cancer

The failure of the second pivotal trial testing Lilly’s Verzenio in prostate cancer was revealed alongside Lilly’s quarterly earnings today, a setback suggesting that CDK4/6 inhibitors are going nowhere in this tumour type. Of the three big pharma players in this mechanism – Pfizer with Ibrance and Novartis with Kisqali – only Lilly had moved into pivotal development, with Cyclone 2 and 3. Such a move was questionable considering the failure of Cyclone 1, which generated a poor 6.8% overall response rate. True, Cyclone 1 was a monotherapy trial and in the pivotal studies Verzenio was combined with Zytiga; data have yet to emerge from the two failed phase 3s, but it seems that any expected synergies didn't emerge. A search of OncologyPipeline suggests that few in the sector hold any hope for CDK4/6 inhibition in prostate cancer, with most work having ended years ago, and not proceeding past phase 2. The only notable industry-sponsored activity is in China at Jiangsu HengRui, whose dalpiciclib is separately approved in that market for breast cancer.


End of the road for CDK4/6 inhibition in prostate cancer?

VerzenioLillyCyclone-3 in mHSPC stopped for futility, Cyclone-2 in mCRPC failed.
KisqaliNovartisNo ongoing company-sponsored work (ph2 data presented at ASCO 2021)
IbrancePfizerNo ongoing company-sponsored work (ph1 trial of KAT6 inhibitor PF-07248144 has Ibrance combination arm)
DalpiciclibJiangsu HengRuiPh1b/3 trial in mHSPC (China)

Note: mHSPC=metastatic hormone-sensitive prostate cancer; mCRPC=metastatic castration-resistant prostate cancer. Source: OncologyPipeline.


Molecular Drug Targets