Platform Trial Looks at Endometrial Cancer Treatment Combinations

A phase II study is investigating olaparib (Lynparza), cediranib (Recentin), durvalumab (Imfinzi), or investigational capivasertib in various treatment combinations in patients with recurrent, persistent, or metastatic endometrial cancer.

In this exclusive MedPage Today video, Bobbie J. “B.J.” Rimel, MD, medical director of the Cedars-Sinai Cancer Clinical Trials Office in Los Angeles, discussed the rationale and design of the phase II NRG-GY012 trial in progress.

Following is a transcript of her remarks:

The study that I presented was a trial-in-progress presentation called GY012. It’s a platform study of endometrial cancer looking at the combinations of cediranib, olaparib/durvalumab, olaparib/capivasertib versus cediranib/durvalumab. So it’s a four-arm platform trial looking for patients with metastatic endometrial cancer who failed primary therapy.

So this is the very first platform study, which means that we already released the first three-arm results. Those were presented at SGO [Society of Gynecologic Oncology] in 2021. And basically what we learned at that time was that the combination of cediranib and olaparib, when compared with cediranib versus olaparib alone — those two arms — that the combination of cediranib and olaparib, although slightly better, did not reach statistical significance for our preplanned endpoint. So cediranib, then, that arm alone rolled over to be the next reference arm for the next four arms.

The four arms are looking at different combinations to compare them to cediranib as the reference arm. The combinations are interesting because they’re combinations both of immunotherapies with either anti-angiogenesis or PARP inhibitor, or the combination of the PARP inhibitor with an AKT inhibitor.

So. the results are expected in approximately a year from now. So. that would be the second quarter of 2024. We anticipate the enrollment to this current four arms of GY012 to close in July of 2023. And we expect it will take us about a year before we’ll have results that are be able to come out. But if we do have the results a little early, we do hope to have them at ASCO [American Society of Clinical Oncology meeting] in 2024.

What we hope that this study will do is give us some indications of the activity of these combination therapies. Obviously, we hope that they are superior to cediranib alone, which is not a terribly effective treatment strategy. We’d like to see something with a progression-free survival of more than 6 months. That’s our goal. We hope that one of these three arms will at least demonstrate to be better than 6 months progression-free survival. We hope that one of these three arms will demonstrate also toxicity reduction compared to the standard of care, which would be pembrolizumab [Keytruda] and lenvatinib [Lenvima], which while a very effective therapy with a 40% response rate, is quite toxic and difficult for patients to maintain over time, leading to discontinuation in about two-thirds of patients.

So, we’re really hopeful that one of these three arms will demonstrate significant progression-free survival benefit, and a toxicity profile that’s improved at least over the standard of care.

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