IDE196 Solid Tumors GNAQ/11 Mutations or PRKC Fusions [2022]
What is IDE196? And How Will It Help Patients With Solid Tumors? Recently, there have been phase 2 clinical data announcements regarding a subset of patients treated in the study. So there were 37 patients treated in a cohort of patients with DVA 300 milligrams twice daily and crizotinib 200 milligrams twice daily. So there were 35 invaluable patients, and excitingly, 89% of patients did have a decrease in their tumor, and the response rate was 50%.
In order for half of the patients to achieve a partial response of greater than 30%, additional clinical data was released that looked at progression-free survival. And although the medium progression-free survival hasn’t been reached yet in patients that were treated in the frontline setting, in patients that were treated with any line of therapy, the medium progression-free survival is about 5 months.
So we know that for patients treated in the frontline setting, this progression-free survival is greater than 5 months. And so, I think this is really encouraging to show that not only are we achieving some great responses for patients and tumor shrinkage, but we’re also showing some durability with this early data of this treatment.
5 Key Takeaways Of The IDE-196 Trial
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The purpose of this Phase 1/2, multicenter, open-label basket study is to evaluate the safety and antitumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors.
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Phase 1 (dose escalation – monotherapy) will evaluate the safety, tolerability, and pharmacokinetics of IDE196 using a standard dose escalation scheme in order to establish the recommended Phase 2 dose. In the Phase 2 (dose expansion) portion of the study, safety and antitumor activity will be evaluated.
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The Phase 1 Tablet and Food Effect Pharmacokinetic (PK) Substudy will evaluate the pharmacokinetic (PK) profile of IDE196 tablet and the effects of food on the PK profile of IDE196 tablet.
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Phase 1 (dose escalation – binimetinib combination) will evaluate the safety, tolerability, and pharmacokinetics of IDE196 and binimetinib using a standard dose escalation scheme and will determine the recommended dose for Phase 2. In the Phase 2 (dose expansion) portion of the study, safety and antitumor efficacy will be evaluated.
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Phase 1 (dose escalation – crizotinib combination) will evaluate the safety, tolerability, and pharmacokinetics of IDE196 and crizotinib using a standard dose escalation scheme in order to determine the Phase 2 dose recommendation. In the Phase 2 (dose expansion) portion of the study, safety and antitumor efficacy will be evaluated.
What Is The Standard Of Care In Patients With Solid Tumors?
2022 has been an exciting year for uveal melanoma with the approval of DIFs or KIMMTRAK, so that’s a frontline treatment available for patients that have HLA-A*0201 status. So that means about 50% of patients with uveal melanoma now have an approved FDA treatment option. So that’s been a really exciting development in the field for patients with metastatic uveal melanoma.
Unfortunately, the response rates were less than 10% and, as I mentioned, only 50%. About 50% of patients with metastatic uveal melanoma are candidates for this therapy. So that means Half of patients will still need an FDA-approved treatment. Even patients who are able to receive KIMMTRAK will almost certainly require second-line therapy.
The other treatment options available for patients are historical treatments with combination immune checkpoint inhibitors (ipilimumab and nivolumab) based on historical data. Patients’ response rates ranged between 15% and 18%. And then it’s looking at clinical trials and trying to determine what’s next and what’s coming for these patients.
Link to the Original Interview: https://oncologytube.com/v/40612
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What Is The Trial Design Of The IDE-196 Clinical Trial?
So IDE196 is actually a molecule that’s been in development for several years. And this is a PKC inhibitor. And so the appeal is that this is inhibiting the activated pathway of GNAQ/11 and activating the mutation that’s found in most patients with metastatic uveal melanoma. So this has been a really exciting molecule.
The challenge has been trying to find a good partner because we know with this targeted therapy that the past successes and response rate have not shown durable responses. And also. The challenges with toxicities have made it difficult to try to push doses due to some of the historical side effects.
So what’s exciting about this study is that it’s looking at relatively low doses of the IDE196, or Darovasertib, and now at a partner with crizotinib. And this is a CME inhibitor. It was added based on some of the data from patient biopsies and looking at other pathways that are upregulated to try to find a good partner for Darovasertib.
What Are The Inclusions and Exclusions of The IDE-196 Trial?
So this has been an ongoing study for several years. Patients, both treatment-refractory and now treatment-naive, were enrolled at various points throughout the study. And so some of those enrollment criteria are evolving as the study stays open. For this patient population, they must have a measurable disease, one that can be followed on study in the liver legion greater than 10 millimeters. Otherwise, patients need to demonstrate just adequate candidacy for a clinical trial. So showing a good performance status, adequate labs, and other screening tests that are completed alongside labs, such as EKG and ECHO, and different tests looking at baseline features of eligibility.
Were There Any Side Effects Reported In The IDE-196 Trial?
The PKC inhibitor IDE196, the several studies that have been investigating this drug have shown GI toxicities of nausea, vomiting, diarrhea, there has also been noted to have rash. Patients can have changes in weight because of those GI toxicities, but I would say those are probably the most common side effects that have been reported.
What Was Surprising About The Updated IDE-196 Trial?
I think, unfortunately, trying to find effective therapies for patients with metastatic uveal melanoma has been really challenging. And so, I think it continues to be exciting to see the number of patients benefiting. And to see these durable responses for patients I think that even as somebody who’s participating in the clinical trial and knowing that some of the patients are benefiting, being able to see that data pulled together across the study has been really exciting to see as potentially a new option down the road and definitely an exciting option for patients.
Final Thoughts On The IDE-196 Trial
I think patients with metastatic uveal melanoma can be rare. But just know that there are exciting trials out there for patients. And both patients, providers, and family members should be looking at clinical trial options and seeking out what may be some available treatments for patients with metastatic uveal melanoma.
Meredith McKean, MD – About The Author, Credentials, and Affiliations
Medical oncology specialist Dr. Meredith McKean, MD, practices in Nashville, Tennessee. During his time as an intern at the University of Colorado, Dr. McKean learned a lot that was useful to her. She works with Tennessee Oncology and the Tristar Centennial Medical Center right now. Dr. McKean is board certified in internal medicine. And is also affiliated with Sarah Cannon Research Institute.