Research Update on Recurrent Low-Grade Serous Ovarian Cancer

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Unknown
Hello and welcome to the research update on recurrent low grade serous ovarian cancer recording. I'm Maggie Nicholas Alexander, the senior director of Gynecologic Cancer Patient Support and Education at Share. For more information about upcoming webinars, support groups and our helplines. Please visit our website at Share Cancer Support dot org. Today we're speaking with Dr. Rachel Gresham about the phase to ramp 201 and the Phase three ramp 301 trials.

00:00:38:00 - 00:01:00:14
Unknown
Before we began, I'd like to hand it over to Dr. Gresham to introduce herself. Hey, thank you so much. Yes. My name is Rachel Gresham, and I'm the section head of ovarian cancer at Memorial Sloan-Kettering Cancer Center in New York. I was also the National PI of the ramp to a one study, and I'm the global PI. Of the 301 study that we're going to be discussing today.

00:01:00:14 - 00:01:34:22
Unknown
Thank you for inviting me. Great. Thank you so much. All right, now, let's dive into the conversation. Can you tell us about the basics of the ramp 201 trial? Of course. Yes. Thank you. So the real 201 study was an international phase two study for women with recurrent low grade serous ovarian cancer who had what we call measurable disease disease we could see on a CAT scan that was at least one centimeter or 1.5 centimeters of a lymph node.

00:01:34:24 - 00:02:13:14
Unknown
Now, patients that enrolled to that study could have received multiple prior lines of therapy, but had to have received at least one prior line of platinum based chemotherapy before enrollment. The study had several different cohorts. The first question that was asked in the study was whether patients would respond better to treatment with a single agent pill called Avuto imatinib, which is a RAF MEK clamp versus a combination of two pills, a brutal imatinib in combination with the second pill called the Deneb, which is a FAK inhibitor.

00:02:13:16 - 00:02:42:23
Unknown
The first patients were randomized to receive just the one pill or the combination of the two pills based on an interim analysis of those first cohorts of patients. It was decided that better response rates were seen with the combination of the two pills than with just one pill. And then the study continued with the subsequent patients that were enrolled to the study receiving both pills, the about imatinib and the defect.

00:02:43:00 - 00:03:26:12
Unknown
Now, this study has now completed accrual, meaning all the patients have been enrolled to the study. But most of these patients, many of the patients still remain on treatment. So additional analysis is ongoing in order to see what the final response rate and benefit of these drugs is. But the first patients that were enrolled to the study, the ones that have been on the study for the longest period of time, have had an interval analysis done to see what their relative response rate was to this combination of drugs, that those results were first reported by my colleague, Dr. Suzannah Banerjee, who's the global PI of the ramp to a one study, and I updated results

00:03:26:12 - 00:04:03:16
Unknown
on this at a subsequent meeting at IG. Yes, a few months ago, showing that these patients that were treated with a imatinib and defect in IB did very well with this combination. Overall, the response rate was 45% and interestingly, those patients that had a cross mutation had an even higher response rate, 60% in these initial results. This, of course, was extremely exciting for all of us that treat patients with low grade serous ovarian cancer because we really haven't seen response rates like this before.

00:04:03:18 - 00:04:27:11
Unknown
Great. Thank you. And is there anything else you can tell us about the findings from the ramp 201 trial? Well, something that I think is really interesting is the tolerability of this combination. Now, MEK inhibitors as a class certainly have toxicity. It's nice that they're pills instead of infusions, but that doesn't mean they don't come without side effects.

00:04:27:13 - 00:05:04:09
Unknown
So MEK inhibitors as a class can cause rash, particularly on the face and chest. They can cause peripheral edema. They can cause vision changes, which are usually temporary. But still, of course, that can be concerning. And then also have other side effects like fatigue and GI side effects like nausea. Now, something that has been really exciting to see is that because these pills are given intermittently, we generally see them to be quite well-tolerated with only a small number of patients discontinuing treatment due to adverse events related to the drugs.

00:05:04:11 - 00:05:27:09
Unknown
And interestingly, we looked at those patients who were more heavily pretreated versus those patients who were less heavily pretreated, meaning patients who'd had a lot of chemotherapy and other treatments before they went on the study versus patients who had had less prior therapies. And we found that the response rate was the same, both in the heavily pretreated patients and the less heavily pretreated patients.

00:05:27:11 - 00:05:52:14
Unknown
So it's really exciting to see that these pills are both pretty tolerable for our patients and an option both for our patients that have relatively newly diagnosed recurrent disease, as well as patients who have been through multiple different lines of treatment. Great. Thank you. And now can you provide an overview of the ramp through one trial? Yeah. Thank you.

00:05:52:16 - 00:06:18:08
Unknown
So based on these very promising initial results seen in the phase two ramp 201 study. It's of course, our goal to continue to gain more information about the use of these drugs in patients with low grade serous ovarian cancer in the hopes of in the future having them approved so that they can be given by prescription. Currently, these drugs are not approved for any indication, so can only be given in the setting of a clinical trial.

00:06:18:10 - 00:06:47:03
Unknown
Now, in order to get to that goal, a new study has been opened called the Ramp 301 study, which is a randomized phase three study for women with recurrent low grade serous ovarian cancer. So this is an international study that's just opening around the globe right now. There are sites open in Australia, Europe, multiple sites open in the United States and soon to be open sites in Asia as well.

00:06:47:05 - 00:07:23:16
Unknown
So this study is similar to the ramp tool. One study enrolls women with recurrent low grade serous ovarian cancer who have had at least one prior line of prior platinum chemotherapy. So that could be carboplatin or cisplatin or even oxaliplatin and some type of platinum chemotherapy, and then can have unlimited additional prior lines of therapy thereafter. So patients on this study are randomized 1 to 1 to receive either these pills to match NEB and a fact to know or to receive a standard of care therapy.

00:07:23:22 - 00:07:51:11
Unknown
And the patient and their physician can decide together which is the best standard of care therapy for them. There's five choices. They can choose weekly paclitaxel chemotherapy. They can choose Doxil chemotherapy, liposomal doxorubicin, which is given IV once every four weeks. They can choose weekly top can chemotherapy, which is given weekly, three weeks on, one week off. Or they can choose Anastrozole Pills or Letrozole pills.

00:07:51:13 - 00:08:17:11
Unknown
Now, oftentimes the patients go on clinical trials. Of course, they're not really wanting to get randomized to the standard of care arm. That's totally understandable. But this study has the option for crossover. So patients who are randomized to the standard of care arm will remain on that treatment for as long as it's helping them. Of course, if their disease is responding to it, we want them to stay on that treatment and they should stay on it for as long as it's it's working and they're tolerating it well.

00:08:17:13 - 00:08:40:23
Unknown
But if a patient develops progression on the standard of care arm, as long as they remain eligible, they can cross over to the acute imatinib and in fact, Neb. So they'll still get the opportunity to receive those drugs. And luckily, we know from that prior analysis of the ramp tool, one study that the response rate was the same and the less heavily pretreated and the more heavily pretreated patients.

00:08:41:04 - 00:09:01:07
Unknown
So we don't think that getting that extra line of standard of care therapies going to decrease their chances of responding to these study drugs at all, which I think is really hopeful for our patients. So we're just opening multiple sites around the world right now. I just had two patients go on study at my site at Memorial Sloan Kettering Cancer Center.

00:09:01:07 - 00:09:24:08
Unknown
So we're so we're really excited to be getting this study up and rolling here and hoping to see many more patients going on around the world in the coming weeks and months. Great. And so if patients are interested in participating in the ramp, 301 trial, how can they get more information about eligibility and joining the study? Yeah, that's a great question.

00:09:24:08 - 00:09:44:04
Unknown
And, you know, I see so many amazing, wonderful women who are so well informed who come to me after they've educated their own physicians about low grade serous ovarian cancer, because, of course, it's a rare disease. And, you know, not not everybody is going to know about every single clinical trial that's open and low grade serous ovarian cancer.

00:09:44:06 - 00:10:14:22
Unknown
So luckily, there are resources available for patients to advocate for themselves and to try to find a location where this study is open. So there is a website for the clinical trial. It's called ramp 301 study dot com. So that's the word ramp ramp 301 study dot com. And of course the is also registered on clinicaltrials.gov and there's a link to clinicaltrials.gov on the ramp 301 Steadicam website as well.

00:10:14:24 - 00:10:40:05
Unknown
And if you go to clinical trials dot gov it gives you the key information about any clinical trial that's currently open including importantly the eligibility criteria. So you can check to see if you meet those key eligibility criteria. And then it also lets lists which sites are currently enrolling. So you can check your state to see if there's a hospital open in your state that has the study open or a nearby state.

00:10:40:07 - 00:11:08:13
Unknown
So that's a great resource to check with and to share with your physician. Great. Thank you. And while I have you here, is there anything else related to low grade serous ovarian cancer you'd like to share with patients? Yeah, I would just say, you know, it's a really exciting time for low grade serous ovarian cancer research. We're finally seeing, you know, clinically meaningful studies coming out showing, you know, new responses, new drugs.

00:11:08:13 - 00:11:35:20
Unknown
And so we've got a lot more options for treatment of this disease than we did have just a few years ago. I would say for our patients with low grade serous ovarian cancer, both for screening for this clinical trial that I'm discussing today, as well as for screening for other potential clinical trials in the future, It can be really helpful to have already had what we call next generation sequencing or tumor sequencing done on your tumor sample itself.

00:11:35:22 - 00:12:05:15
Unknown
This is a type of testing that looks to see what mutations are in your tumor tissue. Now, some patients with ovarian cancer will have had genetic testing done, but that might have only been on their blood or saliva or fingernails. That type of testing is what we call germline testing, and that's a different type of genetic testing. That's primarily to look to see if someone has a Bronco mutation or some other hereditary cause for their cancer.

00:12:05:17 - 00:12:27:08
Unknown
Now, this other type of testing that's done on the tumor tissue itself looks for what we call somatic mutations, which are mutations that are present just in the tumor and not in the normal cells of the body. And for patients with low grade serous ovarian cancer, the most common somatic mutations that we see are those affecting the kinase pathway.

00:12:27:08 - 00:12:50:04
Unknown
So cross or address or address or BRAF mutations. And if one mutations. But it can be really helpful to know what mutations are in your tumor tissue. So if you haven't had that done before, it's a really important thing to talk to your doctor about. This can be done through multiple different platforms. It's a it's a standard of care billable to insurance.

00:12:50:06 - 00:13:09:19
Unknown
So a great thing to talk to your physician about. Great. Thank you so much, Dr. Gresham, for answering all of our questions. We really appreciate you joining us today. Great. Thanks so much. I'm always happy to answer any questions anyone has, though, and on my way.