New Keytruda clinical trial announced - a potentially great new immunotherapy

Next month, recruiting will begin for a great clinical trial for Keytruda (pembrolizumab), the anti-PD-1 immunotherapy. It’s already approved for melanoma, lung cancer, and head-and-neck cancer. Some of you may remember that this is the drug that Jimmy Carter attributes to his melanoma remission.

The really nice thing about this trial is that everyone gets Keytruda. This is only for patients with metastatic castration-resistant prostate cancer (mCRPC). There are 3 cohorts. Patients will get Keytruda with a different combination of medicines depending upon which medicines they’ve used before.

Cohort A (70 patients): Keytruda + Lynparza (olaparib)

Lynparza has demonstrated efficacy in men with certain genetic deficits that interfere with DNA repair (like mutations in the BRCA 1 and 2 genes). Patients must have already had Taxotere (docetaxel) therapy previously. Prior treatment with Zytiga, Xtandi or both is allowed.

Cohort B (70 patients): Keytruda + Taxotere (docetaxel)

This is for patients who have not yet received Taxotere infusions for metastatic PC. Eligible patients must have received prior Zytiga or Xtandi but not both. They must have good performance status.

Cohort C (70 patients): Keytruda + Xtandi (enzalutamide)

Patients must have received prior Zytiga, but not prior Xtandi. They may have received Taxotere for metastatic hormone-sensitive PC, but not for metastatic castration-resistant PC.

Other:
There does not appear to be any exclusion for prior use of Provenge or any other investigational immunotherapy taken at least 4 weeks prior to starting on the study.

Tumor tissue samples must be provided.

There are other exclusions due to certain co-morbidities, and recent use of other drugs. You can check the exclusion criteria in the following link:

/clinicaltrials.gov/ct2/show/NCT02861573

It’s scheduled to start in September, and I hope it will be in multiple locations. It has started recruiting in all locations. If you think you qualify, you may want to forward the link to your medical oncologist and begin discussions about it.

added recruitment update

I just came across a related clinical trial at Peking University in Beijing, China (not that I expect anyone here will go there for it). They are using CRISPR technology to knock out the PD-1 gene from some extracted T-cells from metastatic castration-resistant PC patients. Then they will reinfuse the T-cells with the PD-1-deleted genes together with low-dose cyclophosphamide and IL-2 to enhance the immune response. It's the first time I've seen CRISPR used for prostate cancer in humans. If it works, it can continue to hunt and destroy cancer cells, perhaps indefinitely. If it doesn't work, it can cause a lethal runaway immune response. Should be interesting.

PD-1 Knockout Engineered T Cells for Castration Resistant Prostate Cancer

- Allen

We haven't seen enough back yet on pembro as it pertains to prostate cancer. But this is the right trial for it. They piggybacked some interesting arms and bio collection.

Beth-

It's only Xofigo that they exclude, not RT. I think maybe because it is systemic, and because only some patients would have had it, it may confound the consistency of the results (ie, those who have had it may do better (or worse) than others who haven't had it). I'd imagine too that, because it's systemic, it pours a lot of cancer antigens into circulation that may affect the immunotherapy response in an unpredictable way.

- Allen

Beth,
Xofigo is excluded from many immunotherapy trials because it directly affects bone marrow. Bone marrow produces red and white blood cells and also platelets. But it's the white cells that get weakened that affects the bodies immune system. And that is largely regarded as a disqualifier for immuno-therapies.

This is also why Xofigo is not a good pre-chemotherapy combination. Chemo affects white blood cell counts and Xofigo inhibits their reproduction.

Post Edited (Tony Crispino) : 8/16/2016 1:33:08 PM (GMT-6)

This is great news for everyone.

It seems that Keytruda is still considered effective for solid tumors. The halted trials appear to involve treatment of blood cancers, specifically multiple myeloma.

www.xconomy.com/new-york/2017/06/12/in-a-myeloma-setback-merck-halts-studies-due-to-patient-deaths/

www.telegraph.co.uk/business/2017/07/25/merck-faces-cancer-drugs-setback-ahead-rival-astrazenecas-landmark/

/endpts.com/merck-hit-with-another-late-stage-setback-on-checkpoint-star-keytruda/

All immune boosters and checkpoint inhibitors have the possibility of generating a runaway immune cascade and consequent death. That risk has to be weighed against the benefit of extending life. This is what clinical trials are for: (1) to assess safety (2) to find the optimal and safe dose and (3) to demonstrate efficacy. One always takes a risk in enrolling in a clinical trial, but the benefits include being closely watched and monitored over time, you will be treated with at least the standard of care, drugs you couldn't otherwise get are free, and, by participating, we benefit others who come after us.

I thought I'd bump this up with the mention of a new Keytruda clinical trial. This one is at UCSF is projected to begin in October. In this one, they will biopsy a metastasis to find 25 mCRPC men who have a DNA mismatch repair defect and 25 mCRPC men who have no DNA repair defects. They will get Keytruda and the option of chemotherapy. Patients must be chemo naive or sensitive and have received Zytiga or Xtandi. Keytruda is already approved for DNA mismatch repair defects.

/clinicaltrials.gov/ct2/show/NCT03248570

Tony-

The way I look at it, it's an opportunity for patients in various situations to get a potentially useful drug that they would not ordinarily be able to get and at no cost. I also like the personalized approach that some of these trials are taking.

I wish it proves promising and proves helpful for my father who has metastatic bone disease and PSA 27

Where there is smoke there is fire...Looks like they might have some more work to do on Keytruda before they put it into more wider use....

www.genengnews.com/gen-news-highlights/after-deaths-fda-places-clinical-holds-on-keytruda-combo-trials/81254610