Merck & Co/MSD has pressed the accelerator on plans to set up Keytruda as the go-to cancer immunotherapy for prostate cancer, building on its already dominant position in lung cancer.
Armed with positive data from the phase 1b/2 KEYNOTE-365 trial of Keytruda (pembrolizumab) in combination with other drugs in patients with metastatic castration-resistant prostate cancer (mCRPC), Merck is moving ahead with three pivotal trials of the PD-1 inhibitor alongside AstraZeneca-partnered Lynparza (olaparib), chemotherapy, and anti-hormone drugs.
Prostate cancer is the most common cancer in men, the second most prevalent after breast cancer, and a higher incidence than lung cancer, which has driven Keytruda’s sales to date. And while lung cancer is actually in decline in developed markets as smoking levels reduce, prostate cancer is trending upwards – likely a result of the ageing population.
That combination has made prostate cancer an enticing target for drug developers and in particular those working on cancer immunotherapies, but both PD-1 and PD-L1 checkpoint inhibitors have largely failed as monotherapies.
The hope now is that combinations could unlock the potential of cancer immunotherapy in this form of cancer, by disrupting the tumour and allowing immune cells to mobilise and penetrate the tumour microenvironment.
KEYNOTE-365 data reported at the ASCO Genitourinary Cancers Symposium this week showed that in patients with castration-resistant prostate cancer (CRPC) Keytruda improved the efficacy of Lynparza – a PARP inhibitor not yet approved for prostate cancer but making its way through late-stage testing – as well as chemotherapy with docetaxel and prednisone, and hormone therapy with Astellas/Pfizer’s Xtandi (enzalutamide) without adding to the side-effect burden.
In the Keytruda plus Lynparza arm, 12% of patients had a 50% or greater reduction in PSA, a biomarker which is elevated in prostate cancer. Meanwhile, the chemotherapy combination had a PSA response rate of 31%, while for the Keytruda/Xtandi group it was 26%.
Clinical endpoints also looked encouraging, with six-month overall survival rates of 73%, 96% and 91% respectively for the three treatment groups.
Merck & Co’s Roy Baynes
The data suggests Keytruda could potentially serve as “a foundational treatment” for prostate cancer, said Merck’s chief medical officer Roy Baynes. The company thinks its phase 3 programme is the largest in the PD-1/PD-L1 category in this tumour type.
Merck has competition in this area of course, and arch-rival in the cancer immunotherapy category, Bristol Myers Squibb, reported results at ASCO GU with its double immunotherapy combination of PD-1 inhibitor Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab) in CRPC.
An interim analysis of the phase 2 CheckMate-650 trial revealed a 25% objective response rate (ORR) in patients already treated with first-line hormone therapy but who had not received chemotherapy.
Lead investigator Padmanee Sharma of MD Anderson Cancer Center in the US said the results delivered “strong rationale for the development of combination immune checkpoint therapy for the treatment of prostate cancer, which is considered a cold tumour with few tumour-infiltrating lymphocytes.”
BMS is also trialling Opdivo alongside Clovis Oncology’s PARP inhibitor Rubraca (rucaparib) in prostate cancer, as well as studies of its drug alongside chemotherapy and anti-androgen drugs.