Keynote-676 clinical trial for BCG unresponsive NMIBC, Immunotherapy + BCG

[Joe]

In January 2020, FDA had  approved Pembrolizumab (Keytruda by MERCK) immunotherapy as a treatment for BCG unresponsive NMIBC in the US.  The treatment is for those who did not respond to BCG treatment.  BCG is infused into the bladder so it affects mainly inside the bladder.  Most immunotherapy including Pembrolizumab are administered intravenously so the drug will be delivered to entire body and it will have systemic effects.   The clinical trial had resulted in complete response rate (no recurrence and no progression)  (20-25%) at 2 years.  The end point efficacy was lower than what FDA had required but FDA approved it because there was only one another FDA approved drug – intravesical chemotherapy Valrubicin for BCG unresponsive since 1999.

Keynote-676 clinical trial is also for  BCG unresponsive NMIBC, but Pembrolizumab is given together with additional BCG.   Pembrolizumab is given every 3 weeks and BCG is given every week for 6 weeks followed by 3 weeks maintenance treatment at moths,3,6,12,18,24,30 and 36.    Note that immune checkpoint inhibitor immunotherapy drugs such as Keytruda, Tricentric, and Avelumab are administered by intravenous injection where BCG is instilled into the bladder. So, it is expected that the side effects will be local to bladder and systemic.  As this is Phase III, side effects (toxicity) must had been cleared already in Phase II.

The rationales for starting the KEYNOTE-676 clinical trial are that Pembrolizumab was effective with PD-L1  expressed advanced  bladder cancer.  Also, higher expression of immune check point PD-L1 was observed after BCG treatment in bladder cancer cells and surrounding immune cells, so by inhibiting immune check points, T-cells are expected to kill the cancer cells which are evading from T-Cells.

KEYNOTE-676 clinical trial had started in December, 2018 and  it seems it is still recruiting patients.  There are 135  Study sites recruiting over 1,500 patients. are shown below, which are listed in ClinicalTrials.GOV   Identifier : NCT 03711032 . Canadian study sites are listed below.     https://clinicaltrials.gov/ct2/show/NCT03711032?term=keynote-676&cond=Bladder+Cancer&draw=2&rank=1

BC

Exdeo Clinical Research Inc.  Abbotsford, British Columbia, Canada, V2T 1X8      Contact: Study Coordinator    6048515667
Silverado Resarch Inc.   Victoria, British Columbia, Canada, V8T 2C1                     Contact: Study Coordinator    2505929988

NB

Horizon Health Network  Moncton, New Brunswick, Canada, E1C 6Z8                  Contact: Study Coordinator    5068574780

ONT

Princess Margaret Cancer Centre.   Toronto, Ontario, Canada, M5G 2M9             Contact: Study Coordinator    4169462246

QUEBEC

CIUSSS du Saguenay-Lac-St-Jean – Chicoutimi, Quebec, Canada, G7H 5H6        Contact: Study Coordinator    4185411000
CIUSSS de l Est de L Ile de Montreal – Hopital Maisonneuve-Rosemont  Montreal, Quebec, Canada, H1T 2M4      Contact: Study Coordinator    5142523400×5766
CHUS – Hopital Fleurimont ( Site 0152)  Sherbrooke, Quebec, Canada, J1H 5N4      Contact: Study Coordinator    8193461110×12827
CHU de Quebec – Hotel-Dieu de Quebec   Quebec, Canada, G1R 2J6                    Contact Study Coordinator    418525444420414

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