There are few radiopharmaceuticals in clinical trials in the US (although there are several in use in Germany), so when a new one is announced, we take notice. Iodine-131-MIP-1095 (1-131-MIP-1095) has had a very limited clinical trial in Germany in 28 patients, and will now be tried in the US, starting at the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York.
Like lutetium-177, iodine-131 is a beta-particle emitter (see this link). Its beta-particle energy is somewhat higher, so that it can penetrate greater distances through tissue — up to 3.6 mm, compared to 1.9 mm for Lu-177. This is an advantage in that it can destroy larger tumors, but it is a disadvantage in that it may destroy more healthy tissue, with the potential to cause hematological and renal side effects. It is also similar to Lu-177 in that its uptake in human tissues can be detected using a gamma-ray camera or SPECT detector. Because gamma-ray detection does not afford the image quality that PET/CT does, it may be combined with a positron emitter, iodine-124. Lu-177 is sometimes combined with gallium-68 for the same purpose. This combination of therapeutic and diagnostic agents (sometimes called theranostics) may be useful in tailoring the dose to the patient based on individual uptake characteristics.
The molecule (or ligand) that the I-131 is attached to is MIP-1095. MIP-1095 is attracted to the PSMA protein on the surface of 95 percent of prostate cancer cells. Although it is highly specific for prostate cancer, there are other tissues that express PSMA, especially the salivary glands and lacrimal glands. It is excreted by the liver and kidneys, and may show up in the intestines, and the lower urinary tract. The dose to the kidneys may limit the amount of the pharmaceutical that may be given to the patient.
A group from the University Hospital Heidelberg (Zechman et al.) treated 28 metastatic castration-resistant patients with I-131-MIP-1095 with the following results:
- In 61 percent, PSA was reduced by > 50 percent; this is better than the response seen with Lu-177-PSMA-617 in these trials and in this one.
- PSA decreased in 21/25 patients, increased in 4/25.
- 85 percent had complete or moderate reduction of bone pain.
- 25 percent had a transient slight to moderate dry mouth, which resolved in 3 to 4 weeks.
- White blood cell count, red blood cell count, and platelets declined during treatment, but there were only three cases of grade 3 hematologic toxicity, often in patients with low blood counts at baseline.
- No renal toxicity was observed.
- The effective dose to cancer cells was higher than for Lu-177-PSMA-617; red marrow and kidney doses were similar, and liver dose was lower.
The clinical trial that is now recruiting at MSKCC, is a Phase I trial to find the best dose of I-131-MIP-1095 among patients with metastatic castration-resistant prostate cancer. Doses will be administered 12 weeks apart for up to five cycles or until dose-limiting toxicity is observed (monthly assessments). Interested patients in the New York City metropolitan area should call the contacts listed on the bottom of this trial description (NCT03030885).
Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.
Filed under: Drugs in development | Tagged: Iodine-131-MIP-1095, radiopharmaceutical, Treatment |
THE "NEW" PROSTATE CANCER INFOLINK 
One of the lutetium trials used a 2-month interval between courses. At least a third of the patients progressed between the first and the third cycle and were taken off lutetium. A study in Vienna used 1-month intervals between cycles and found no increased toxicity from the more dose-intense schedule. I believe the reason for Sloan-Kettering choosing 3-months intervals reflects the more aggressive radiation. But the consequence might be that more than half the patients will progress between the cycles. Therefore I fear it will be difficult to understand why the US hospital chose the iodine-131 radiation when we have more results with lutetium.
Dear Finn:
I think that has more to do with who was paying for the study tthan anything else. This is a study sponsored by the manufacturer of the iodine-131 product. MSKCC has only “chosen” to do a trial of the type that the manufacturer was interested in having done.
At this point in time, e want to be able to find out how well any and all of these products work. If we can find that out, then we can worry about comparative data. This is a Phase I pilot study. From a clinical outcome point of view it means relatively little except to help us understand what the maximum tolerable dose is when given at 3-month intervals.
FYI
It appears (at least to my reading of the trial) that prior use of Ra-223 makes you ineligible for this trial.
Hi Bill, and yes, your reading of the trial’s exclusion criteria would indeed seem to mean exactly that.
Hi Mike.
There does not seem to be any PSMA-617 radioligand therapy available in the US in clinical trials. I am in the process of being evaluated for treatment in Germany. They have asked me to get a PSMA PET and send them a image of the MIP. It seems like John Hopkins may be able to do the scan but only as a clinical trial. I am pursuing getting them to do the scan. UCLA also can do the scan if Johns Hopkins does not come through. I have been “told” that US-based trials are coming, but most likely sometime in 2018. The beat goes on.,
Bill
Bill:
For some reason the US does not appear to be on the “cutting edge” of research in this area.
Bill,
There is a clinical trial of Lu-177-PSMA-617 but only for men with castration-resistant prostate cancer (CRPC) who are not detectably metastatic. Scott Tagawa, the lead investigator, is working on a new trial among men who are metastatic and CRPC.
As far as PSMA diagnostics go, the most accurate one so far, DCFPyL, has entered a nationwide clinical trial (OSPREY). It’s already available at Johns Hopkins, Yale, Dana Farber, and Washington University, and will be available at other locations shortly. The next best PSMA-based PET is the Ga-68-PSMA-11 PET/CT. It is available at UCLA, UCSF, Stanford, and the Cleveland Clinic. I know UCLA is charging $2,650, which is their cost for the radioindicator. UCLA is only offering it for biochemically recurrent prostate cancer so far (NCT02940262). UCSF is also testing a PSMA PET/MRI called CTT1057 among men with mCRPC.
Hi Allen.
Thanks for the information.
Germany still seems like my best chance for treatment within my current lifespan guesstimate?
I think the stuff Dr. Tagawa is working on is a bit different from what I am looking for at this point.
I am not sure if the scans in the OSPREY trial will give me the information needed by the doctors at Heidelberg University Hospital, but since my oncologist is one of the sub-investigators I will ask him. I have already reached out to Hopkins and I am waiting.
Thanks again for the help. I will let you know what I find out.
Bill
I was just told by a patient that the OSPREY trial is free of cost.