Anti PD1 for PDL1 Negative Patients? - 1259579

We have MK-3475 (Merck anti-PD-1, formerly known as lambrolizumab) trials open at our center but not for lung. However, I am active in the other three companies's trials:

1. MEDI4736, MedImmune's promising anti-PD-1 drug, does not require PDL1+ status. This is a Phase I/II single-agent trial. We also have a Phase I trial of MEDI4736 + tremilimumab.

2. MPDL3980A, Genentech/Roche's promising anti-PD-L1 drug. This requires PD-L1+ status with certain exceptions. We have this open as a Phase I/II trial.

3. Nivolumab (BMS-936558), Bristol-Myers Squibb's promising anti-PD-1 drug, we have open as single-agent and also in combination with Yervoy (ipilimumab) as a Phase I/II trial. This does not require PD-L1 positive status. We also have a trial of nivolumab plus anti-KIR antibody, and nivolumab plus IL-21, as well as Yervoy plus anti-KIR antibody.

In addition, we also a few Phase III randomized trials with these agents vs chemo, but the downside with those is that one cannot be certain of getting the actual study drug. Overall, I suggest clinicaltrials.gov search for centers offering active nivolumab or MEDI4736 trials. Hopkins or Memorial-Sloan Kettering may be safe places to start. The other factor is that one may need to be prepared to wait for a few weeks for a slot to open up for you.

Dear Drs.

I am wondering how prevalent is this PD 1 in lung cancer? Is this present in 10% or 80% of lung ca patients? Is it more in non small cell or squamous. What are the characteristics of patients with PD 1 receptors? are they generally non-smokers?

thanks

ssflxl

PD-L1 appears to be present in something in the range of 40-50% of NSCLC cases, though the diagnostic testing is still evolving, and i's not clear how PD-L1 positivity should be defined. In the trial of MPDL-3280A presented by Dr. Spigel at ASCO this year, it was more like 1/3 of lung cancer patients who were considered as PD-L1 positive.

-Dr. West

Dr West

Do you know if PD1/PDL1 is available for commercial testing? I was just wondering if I could have my Dad tested for it so that we can hopefully try to have that treatment lined up (beg, borrow, steal) if we ever need it.

Tvoltagg, many thanks for the tip, I suppose I will KIV this and await further developments. My best wishes to you and your wife on the biopsy results.

In my limited experience and from reading, it seems much fewer, eg 20-30% of patients end up being 'PD-L1 positive'. I agree it is aggravating for patients to wait several weeks, give up a boatload of archived tissue, and then find out they are ineligible while their cancer progresses. The other aspect is that leftover tissue may then be sold by some of these pharma companies to other medical research companies.

This is why we also have trials that don't require staining of tissue to enroll.

There is currently no point is getting your tissue PD-L1 tested outside of a trial, because each company has their own proprietary test. They will not accept the results of any other assay for trial entry. It is conceivable for Merck's vendor PD-L1 test to be negative, and then Genentech's to be positive, or vice versa.

Also, the PD-L1 test is still a work-in-progress. It is not a clean test like EGFR PCR. Instead it is kind of like the estrogen receptor test in breast cancer, prone to a lot of variability.

Dr. Creelan

That's kind of scary- if you test neg for one but positive for another because of a different testing method. so does that mean if you don't qualify for one trial because you are tested negative, you can still try another trial with a different company that may do the testing in a different way!!

ssflxl

Hi Gang,

In attempting to enroll in Genentech's MPDL3280 Anti-PDL-1 trial, my archived tissue tested negative for PDL-1. I was told that because I had chemo recently, fresh tissue might actually test positive for PDL-1, as chemo seems to stimulate expression of PDL-1. Importantly, I was informed that Genentech's test is different/more sensitive than Merck's test, and some patients who have tested negative with Genentech wound up being positive on Merck's test, as Dr. Creelan points out.

Merck's trial has several arms. Arm C was for PDL-1 negative lung patients, and that cohort filled quickly across the nation. Only Arm F seems to be open now, which is for PDL-1 positive lung pts. Genentech's trial has 3 cohorts - 1 for brain mets, 1 for 1st or 2nd line, and 1 for general pretreated (I think that's how it's divided but not sure). I'm not aware of what exceptions there are to the PDL-1 requirement. The trial doc said she had 6 patients rebiopsied and only 1 came up positive the 2nd time around, but said I might be positive because of the chemo. Since I stopped chemo in May and have continued on Tarceva, I don't know if being 5 months away would still mean I might express PDL-1... If someone could enlighten me that would be great, as I'm getting ready to schedule that biopsy at Angeles Clinic...

Thanks,
Jazz

JAZZ

thanks for your information. I sure hope that this stuff gets through the trials quickly since they can fill up the trials easily. i hope it can get rapid FDA approval next year, so that we don't have to deal with the different trial requirements.

ssflxl

Is there any relationship between low Lymphocyte counts and the existence of adequate PDL1 on tumor cells? And are normal Lymphocyte counts any predictor of response for those PDL1 positive 2/3 once chemo has been cleared from body?

We don't yet have answers to any of these kinds of questions. These are new treatments we have never given before, so at this point we don't really have knowledge of all of the potential correlates of response with treatments that are just being given for the first time to cancer patients.

-Dr. West

Dear Dr. Creelan,

Thanks very much for sharing the trials that are open currently at your institute.

You mentioned that MK-3475 is currently recruiting patients other than lung cancers. I wanted to check if you're enrolling ovarian cancer patients ( a family nember has it) for this trial.

Also wondering if tremelimumab + MEDI4736 and Nivolumab + IPI combination trials will be available for ovarian cancer patients in the coming future ( either on the same trial or another separate trial ? Someone mentioned to us that Ovarian cancer was on their combination list and perhaps may start recruiting ovarian pts by end of the year. If you could confirm if these would be available at your institute and when ; that would be very helpful for a family member of mine.

Many thanks

Andy

Hi Andy, I'm very sorry about your family member. I won't speak for Dr. Creelan but it may be easier to get that information from the ovarian cancer specialists at Moffitt. Most trial researchers are eager to enroll so are very helpful.

All best,
Janine

Thanks Janine, I greatly appreciate your response.

The reason I ask is most cancer centers running these immunotherapy trials have set -up a dedicated immunology group; being led by lung/melanoma/renal experts (since they have the most experience with these agents) and they see other cancer types as well through this group.

I'd greatly appreciate Dr. Creelan's views. If I could add a question, when would the tremelimumab+medi-4736 phase I trial start at your institute?

many thanks in advance

Does the testing have to come from solid tumor or can fluid taken from a pleural effusion be tested?

Sometimes there's enough cells found in the fluid to do testing, sometimes not. Perhaps the pathologist can go back through all the fluid and gather up enough for the test.

I'd do just about anything to keep my husband from having another biopsy; none of the 5 he's had came up with anything more that a pneumothorax except for the open thoracotomy biopsy needed just for dx. D's an outlier in many ways. I've enjoyed the way his cancer is so indolent and the way he's responded but not so much the way his biopsies have gone. :wink: BTW, results tomorrow from CT, wish us luck. I wish you both the best (no biop),
Janine

Andy, I'll assume you got your answer but wanted to say I'm sorry for missing your last question.
Never hesitate to bump up the thread or somehow poke us if we don't answer. It's not because we're ignoring you we missed it. (first time for everything)

Keep us posted, let us know if you still have questions,
Janine

I don't presume Andy's question got answered, but I don't know that Dr. Creelan would know...the regulatory process is often pretty opaque to those of use who focus on treating the actual patients. If Dr. Creelan isn't leading the trial effort, he may find out only when the trial becomes available.

You may get further by reaching out to the clinical research folks at Moffitt Cancer Center.

-Dr. West