ECLIPSE: A Phase III trial of Lutetium radioligand for mCRPC

 

Treatment of prostate cancer has changed dramatically over the years, with  multiple treatment options including chemotherapy, refined hormonal therapies, radiotherapies, surgery and others currently available, depending on the patient and their disease.

 

Dr Sakir Mutevelic, Chief Medical Officer at Curium, has witnessed the tremendous progress in cancer treatment options and the increased survival rate that goes with them.  Today, we’re talking with him about an investigational treatment for metastatic castration resistant prostate cancer in development at Curium, that could be a valuable new asset in disease management.

 

Information for clinicians about the Eclipse trial is available here.

 

For patients, a web portal with more information is available here.

 

All trial data is available at:  https://clinicaltrials.gov/ct2/show/NCT05204927

 

Image source: Heiti Paves/ Shutterstock

 

 

Transcript:

 

The following transcript is automatically generated

 

00:00:05 Will Mountford 

Hello I’m Will mountford. Welcome to researchpod, the diagnosis management and survivability of prostate cancer has changed dramatically since the first characterization of androgen receptors in the late 1960s. 

00:00:18 Will Mountford 

Today, depending on the patient’s diagnosis, clinicians may have multiple treatment options, including chemotherapy, refined hormonal therapies, radio therapies, surgery, and others. 

00:00:29 Will Mountford 

Doctor Sakir Mutevelic, chief medical officer at Curium, has been working with patients for over 20 years. 

00:00:36 Will Mountford 

He has witnessed tremendous progress in cancer treatment options and the increased survival rate that accompanies them. 

00:00:41 Will Mountford 

He has seen what those innovations in medicine mean in terms of real human life. 

00:00:46 Will Mountford 

Today we’re talking with him about an investigational treatment for metastatic castration resistant prostate cancer in development at curium, a world leader in the nuclear Med. 

00:00:56 Will Mountford 

This investigational therapy could become an important tool for clinicians and their patients when treating prostate cancer. 

00:01:05 Will Mountford 

And joining me to discuss his work from Curium Pharma is Doctor Sakir Mutevelic. 

00:01:09 Will Mountford 

Sakir, hello. 

00:01:11 Dr Sakir Mutevelic 

Nice to meet you. 

00:01:12 Will Mountford 

Thanks very much for your time today. 

00:01:14 Will Mountford 

Could you tell us a bit about yourself? 

00:01:15 Will Mountford 

Some of your background, your professional history and what’s led you to your work in radiopharmaceuticals? 

00:01:21 Dr Sakir Mutevelic 

So thank you, will. I’m a medical doctor and pharmacologist by background, with over 25 years of professional experience in Pharmaceutical industry and more than 20 years in oncology. 

00:01:32 Dr Sakir Mutevelic 

I’ve joined curium as chief medical officer in late 2021, which is great honor for me to join curium, the world’s leading local medicine company that is redefining the experience of cancer by including the way cancer is diagnosed and treated. 

00:01:49 Dr Sakir Mutevelic 

It’s a very, very exciting time for nuclear medicine, oncology in particular. 

00:01:54 Dr Sakir Mutevelic 

And we at curium our committed to continuous innovation in research and development. 

00:01:59 Dr Sakir Mutevelic 

We are focused on basically what is most important, namely improving the life of patients as well as their families. 

00:02:07 Dr Sakir Mutevelic 

And I’m proud to be part of the company. 

00:02:09 Dr Sakir Mutevelic 

It is making that’s different. 

00:02:11 Dr Sakir Mutevelic 

As well as helping and supporting the healthcare professionals, of course in their diagnostics and treatment efforts every day. 

00:02:23 Will Mountford 

Well, on that note of treatment, the specialty that you have and that we’re talking about today is in radiopharmaceuticals, if you give us maybe a brief history of the treatment landscape for prostate cancer and what has led to the development of radiopharmaceuticals as an option that we’re exploring today. 

00:02:41 Dr Sakir Mutevelic 

Ohh, with pleasure. 

00:02:42 Dr Sakir Mutevelic 

Years ago the prostate cancer diagnosis as well as treatment based on this diagnosis was based on surgery mostly and it was often a time of little complications. 

00:02:58 Dr Sakir Mutevelic 

Over the prime treatment of prostate cancer evolved to systemic chemotherapy or radiation approaches in some cases. 

00:03:06 Dr Sakir Mutevelic 

Then, the field then progressed using targeted hormone therapy. 

00:03:11 Dr Sakir Mutevelic 

This hormone therapy would cut off the supply of testosterone for the cancer. 

00:03:16 Dr Sakir Mutevelic 

Today we have different precision. 

00:03:19 Dr Sakir Mutevelic 

Therapy modalities. 

00:03:21 Dr Sakir Mutevelic 

One of those is radiopharmaceuticals. 

00:03:24 Dr Sakir Mutevelic 

And we experience in this space as being expected nuclear medicine and living our vision basically to redefine the experience of cancer through our trusted legacy in nuclear medicine. 

00:03:38 Dr Sakir Mutevelic 

The role of radiopharmaceuticals is the recent one and the last five to seven years as a part of precision therapies and then short very simply described targeting specific. 

00:03:52 Dr Sakir Mutevelic 

Receptors at the surface of cancer cells by so-called ligands and those ligands are coupled to the different trigger isotopes and the most permanent one recently is lutetium 177 and as a as a radio from a suitable conjugate reaches, the receptor is docking to the receptor. 

00:04:12 Dr Sakir Mutevelic 

At the surface of the cancer cell. 

00:04:14 Dr Sakir Mutevelic 

And the radioisotope with the directed radiotherapy at the level of cancer cell internalizing the cancer cell and destroying the cancer cell. 

00:04:22 Will Mountford 

What would the typical patient journey as much as there is anyone typical patient journey look like if they were suspecting that they were ill, if they wanted to come to a doctor, get their opinion and wound up being diagnosed with prostate cancer and especially metastatic disease. 

00:04:39 Dr Sakir Mutevelic 

That’s a great question. If I would take the patient’s first time presented with the suspicious on prostate cancer, those are the patients who are. 

00:04:51 Dr Sakir Mutevelic 

Getting the PSA elevated PSA’s, prostate specific antigen and at seen by physician force and the another alert is getting there. If the PC is elevated. 

00:05:06 Dr Sakir Mutevelic 

And the disposition could be primary care physician, but also urologists or medical oncologists pending at what stage and level patient was presented to the physician. 

00:05:20 Dr Sakir Mutevelic 

As the patient having the elevated PSA, which has not said it’s suspicious to the cancer and may not be directly related in some certain cases, the next step is to do the so-called diagnostic imaging study to basically try to see whether something is happening. 

00:05:40 Dr Sakir Mutevelic 

And and and and a plastic. 

00:05:42 Dr Sakir Mutevelic 

Or there is indication for doing the biopsy of the prostate. 

00:05:47 Dr Sakir Mutevelic 

If it is confirmed by a biopsy that it is a prostate cancer. 

00:05:52 Dr Sakir Mutevelic 

Then depending on stage of the prostate cancer, the patient will be specified either as hormone sensitive or so-called castration resistant prostate cancer patient the patients are treated at the beginning with the hormone therapy, so those are the testosterone suppressing medications, hormone therapies, agents. 

00:06:13 Dr Sakir Mutevelic 

Or with the targeted radiation therapy. 

00:06:16 Dr Sakir Mutevelic 

Or, depending on stage of disease, simple observation to the next examination of PSA. 

00:06:22 Dr Sakir Mutevelic 

If it is still elevated or it has been normalized as the this is potentially is progressing, the PSA can rise again and then potentially the second hormone therapy such a better their own or and sodomite. 

00:06:37 Dr Sakir Mutevelic 

Given and, if the PC again raising. 

00:06:41 Dr Sakir Mutevelic 

Again, the imaging studies and imaging agents I use for those imaging studies are done and if the region is seen outside the prostate, then it may be considered as metastatic and then being treated as metastatic prostate cancer. 

00:06:56 Dr Sakir Mutevelic 

So there are different stages of more sensitive. 

00:07:01 Dr Sakir Mutevelic 

Prostate cancer, as well as the stages of castrational resistant, which in both cases could be non metastatic and metal. 

00:07:09 Will Mountford 

At that metastatic stage, I understand that is when the Eclipse trial that we’re talking about today comes into play. 

00:07:15 Will Mountford 

So in terms of just an overall view of what is involved in that trial and the overview of that and we can explore some of the details in a moment. 

00:07:24 

This is our. 

00:07:26 Dr Sakir Mutevelic 

Phase three confirmatory study of lutetium 177 present, 90 in metastatic castration resistant prostate cancer patients who are so-called chemotherapy naive so have not been treated with chemotherapy in the station resistant prostate cancer setting. This is a multi center. 

00:07:45 Dr Sakir Mutevelic 

Randomized open label study. 

00:07:48 Dr Sakir Mutevelic 

And we’re conducting this study in the US as well as in Europe. 

00:07:53 Dr Sakir Mutevelic 

It’s still the product and the investigation has not been approved by any regulatory body, has said. 

00:07:59 Dr Sakir Mutevelic 

It’s in a of matory phase three clinical development. 

00:08:04 Dr Sakir Mutevelic 

The studies, of course, done by partnership between oncologists missiologists as well as nuclear medicine physicians at different clinical trial sites in the US and Europe. 

00:08:18 Dr Sakir Mutevelic 

There are different criteria for patient reliability, but I would like to emphasize here that this metastatic surgery listen patients cannot have had any treatment with the second endogen access receptor targeted treatment or to be treated with chemotherapy from the trial design. 

00:08:38 Dr Sakir Mutevelic 

Just in the short and the endpoints, this is, as I said, multicenter open label randomized study in a 2 to one treatment ratio. 

00:08:47 Dr Sakir Mutevelic 

That means that the patients have a higher possibility to be randomized in the treatment arm. 

00:08:54 Dr Sakir Mutevelic 

As well as a control arm arm. 

00:08:57 Dr Sakir Mutevelic 

There is also. 

00:09:00 Dr Sakir Mutevelic 

If the patient is randomized in the control arm. 

00:09:03 Dr Sakir Mutevelic 

That the patient if progress and when progress at the control has a opportunity, if it’s agreed to go for it mainly to cross over mainly to be treated with the Fisher 177, PS MIT in a crossover manner. And I mentioned the term confirmatory. 

00:09:24 Dr Sakir Mutevelic 

Phase three study that means that this study will prove. 

00:09:30 Dr Sakir Mutevelic 

At the end of the study, the product could be effective and safe for treatment of patients in a clinical setting, both in the US and Europe. 

00:09:44 Will Mountford 

Now just to compare some abbreviations we discussed PSA earlier and PSMA is a target in the trial design for Eclipse. 

00:09:53 Will Mountford 

So could you remind me and everyone listening at home how those two are different and why PSMA is of value? 

00:09:59 Will Mountford 

In the Eclipse trial design. 

00:10:02 Dr Sakir Mutevelic 

Yeah, but this is a very good question, and the frequently asked obviously the PSA abbreviation means plus the specific membrane antigen which is present at the surface of the prostate cancer cells. 

00:10:17 Dr Sakir Mutevelic 

And this is very valuable between talet just to remind us and all of us in the audio. 

00:10:25 Dr Sakir Mutevelic 

The percentage of men expressing the PSMA prostate specific membrane antigen in metastatic castration resistant prostate cancer is about 85%. So very high number. 

00:10:36 Dr Sakir Mutevelic 

How this radiopharmaceutical radioligand therapy PSMA directed compound works? 

00:10:43 Dr Sakir Mutevelic 

As I mentioned, in general, the Radioligand therapy works well. 

00:10:48 Dr Sakir Mutevelic 

Ligands which could be peptides, antibodies, nano antibodies, those ligands are binding to the PSMA in the prostate specific membrane antigen. 

00:10:59 Dr Sakir Mutevelic 

When they bind, the compounds are carrying form of conjugate the radioisotope for the directed radiotherapy at the cancell level. 

00:11:11 Dr Sakir Mutevelic 

And talking of ligand to the PCA enabling the radioisotope to be taken up by the cancer cell. 

00:11:19 Dr Sakir Mutevelic 

And bring the radioactive agent for directed radio terapy at the cell level to destroy the DNA of the cell and kill the cancer cell. 

00:11:28 Dr Sakir Mutevelic 

So there is a limited time to radioactive agent due to the half life of radioactive agent and this limited time of radioactive agent in the body and that is specific to the cells expressing the PSA and the basically the collateral damage to the other cells is limited. 

00:11:46 Dr Sakir Mutevelic 

Unlike some other treatments like chemotherapy. 

00:11:48 Dr Sakir Mutevelic 

Or or other treatments. 

00:11:50 Will Mountford 

Now as a question that’s probably going to cross any patient’s mind when they are considering either entering. 

00:11:56 Will Mountford 

Trial or, you know, talking about prostate cancer is the idea of being injected with something radioactive. 

00:12:02 Will Mountford 

Is, well, frankly, quite a scary one. 

00:12:05 Will Mountford 

So in terms of how safe and effective and targeted the Lutetian based treatment is. 

00:12:13 Will Mountford 

Why and how is it better than going for radiotherapy or chemotherapy or targeted therapy? 

00:12:20 Will Mountford 

As you know, each of those individually when it seems to combine ideally the best parts of all of them together. 

00:12:27 Dr Sakir Mutevelic 

So the answer is very simple. 

00:12:29 Dr Sakir Mutevelic 

At the doses of the radioactive isotope coupled to the ligand is safe as being directed to the cancer cell at the doses and the half life of the radioisotope, which is basically very much comparable to external beam radiation. 

00:12:48 Dr Sakir Mutevelic 

That means the radiation. 

00:12:50 Dr Sakir Mutevelic 

In any other treatment of the cancers, as well as certain types of prostate cancer, that’s well, well known radiation therapy, which because it’s external one. 

00:13:00 Dr Sakir Mutevelic 

The interesting point of directed radio live and therapy is. 

00:13:06 Dr Sakir Mutevelic 

Specificity to the specific receptor at the cancer cell surface. 

00:13:13 Dr Sakir Mutevelic 

As well as safe dose of the radio isotope coupled and reaching the cancer cell itself. 

00:13:21 Dr Sakir Mutevelic 

With a limited activity at the receptors outside of the cancer cell, or in this case, perfect cancer cell. 

00:13:31 Dr Sakir Mutevelic 

It’s also very well tolerated and has been proven very, very well tolerated in the earlier stages of clinical development, which led and lead not only this compound in the CLIP study, but any other radioligand therapy compound into the confirmatory phase three study for the purpose of growing the figures in safety for the purpose. 

00:13:52 Dr Sakir Mutevelic 

Of getting it approved parallel to authorities. 

00:13:55 Dr Sakir Mutevelic 

And also used broadly at any Community level and hospitals treating their prostate cancer in this case. 

00:14:08 Will Mountford 

If there are any clinicians listening to this who want to know more about engaging in the trial, being participant clinic, or if there’s any patient out there who thinks that they might be a candidate for this, like you say, if they haven’t had that second arrat therapy and they want to explore being part of this trial with their. 

00:14:26 Will Mountford 

Why is eclipse the right trial for them? 

00:14:29 Will Mountford 

Why does it come at the right time and where can? 

00:14:31 Will Mountford 

They find out more. 

00:14:34 Dr Sakir Mutevelic 

So TIP study is actively enrolling patients. 

00:14:37 Dr Sakir Mutevelic 

So if there are the clinicians who are listening and want to learn more about the study, there is a healthcare professionals website where they can get some information on the trial itself on clinical trial sites involved as well as eligibility criteria for patients. 

00:14:54 Dr Sakir Mutevelic 

You can find it under Eclipse clinical trial dot. 

00:14:58 Dr Sakir Mutevelic 

There is also patient uh website available where there is an initial screening questionnaire available and if patients qualify to the initial Screener, they will be contacted by medical professionals, not company ones, but those from the clinical trials site for the evaluation. 

00:15:17 Dr Sakir Mutevelic 

So this patient. 

00:15:18 Dr Sakir Mutevelic 

That could be found under the curium eclipse trial dot org and of course is any other physical company. 

00:15:27 Dr Sakir Mutevelic 

The Eclipse study is also placed at the clinical trial dot. 

00:15:33 Dr Sakir Mutevelic 

You had the description of the study as well as the inclusion exclusion criteria could be found as well as a list of connected sites involved. 

00:15:44 Will Mountford 

Doctor Mutevelic, thank you so much for your time and look forward to hopefully hearing more about the success of this. 

00:15:49 Will Mountford 

Trial soon. 

00:15:50 Dr Sakir Mutevelic 

Thank you very much and looking forward to meeting you next time with the results of the study. 

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