Advertisement


Ursula A. Matulonis, MD, and Nicoletta Colombo, MD, on Ovarian Cancer: Overall Survival Data on Relacorilant Plus Nab-Paclitaxel

2022 ASCO Annual Meeting

Advertisement

Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and Nicoletta Colombo, MD, of the University of Milan and the European Institute of Oncology, discuss phase II results on the overall survival benefit of intermittent relacorilant, a selective glucocorticoid receptor modulator, combined with nab-paclitaxel, compared with nab-paclitaxel alone in patients with recurrent platinum-resistant ovarian cancer. A phase III trial comparing intermittent relacorilant plus nab-paclitaxel with investigator’s choice of chemotherapy in primary platinum-refractory disease is ongoing (Abstract LBA5503).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Ursula Matulonis: Nicoletta great to see you. Congratulations on this study. It's a really fascinating study with really intriguing results. Can you tell us about the mechanism of action of Relacorilant and how it inhibits ovarian cancer growth? Nicoletta Colombo: It has been shown that cortisol main use chemotherapy resistance by interfering with some apoptotic pathways, which cytotoxic agents such as Nab-Paclitaxel utilize. So basically Relacorilant is a selective glucocorticoid receptor modulator, and binds to the GI, the glucocorticoid receptor and suppresses the activity of cortisol. So in this way, of course, cytotoxic agents, such as Nab-Paclitaxel may use their apoptotic pathways and induce apoptosis and cells deaths. So that's the rational for using this drug in ovarian cancer patients. Ursula Matulonis: Yeah. It's a really unique, unique mechanism of action that I don't think's really been tested before. Nicoletta Colombo: No, it's really unique. It's very interesting because even very low level of cortisol may really induce chemotherapy resistance. So by suppressing this activity of cortisol, we may enhance the efficacy of cytotoxic agents. Ursula Matulonis: And in this trial, so there were three arms. There was control Nab-Paclitaxel and then two different schedules of Relacorilant added to Nab-Paclitaxel. Can you just, did you talk about those two different schedules and why they were tested? Nicoletta Colombo: Yeah. One schedule was just very, I mean, low level of continuous Relacorilant and the other one was Relacorilant given the day before, the day off, and the day after chemotherapy. Why that? Because on one end, continuous administration may provide a continuous antagonist of cortisol, but on the other hand, by giving higher dose of Relacorilant around times of maximum chemotherapy exposures may provide a better antagonist. So that's why we decided to use or to test these two different schedules. Ursula Matulonis: Yeah. Gotcha. And tell us about the results which are intriguing and I think really promising. Nicoletta Colombo: Yeah, this is a randomized phase two, and we enroll 178 patients in these three arms. So the comparator arm, which was Nab-Paclitaxel alone given the day 1, 8, 15 of a 28 day cycle. And then we have the two Relacorilant arm, the intermittent and continuous. These patients were really very heavily retreated patients up to five prior lines of chemotherapy. All but one had received prior taxane. More than 50% had received bevacizumab. And about one third had received even PARP inhibitors, so really a very, very heavily pretreated population. Moreover, 36% had a platinum refractory disease, and some of them even primary platinum refractory disease. And actually there was an unbalance on the percentage of patients with primary platinum refractory disease, which was higher in the intermittent scheduling arm. So, so patients were randomized in these three arms, and then the primary endpoint was progression free survival. And we presented already the data at ESMO last year, and we demonstrated a significant improvement in progression free survival for patients receiving the intermittent schedule of Relacorilant. And so this was the primary endpoint, but today, I mean at this conference, I will present the overall survival data. And it's very interesting because already at that time, we saw a trend for an improvement in overall survival. And this trend has been now confirmed. Actually, we see that for the intermittent schedule compared to the standard arm, we have a hazard ratio 0.67, which does not reach really statistically significant, but is very close. But what we did the scenes, as I said, there was an imbalance in the primary platinum refractory patients population, we perform subgroup analysis taking away the primary platinum refractory. And in this situation, the hazard ratio is 0.63 and becomes statistically significant. So I think this is a great news because we know that patients with platinum resistant ovarian cancer represent a very high unmet need. And we now have a completely different drug with a very unique mechanism of action, which can potentiate the efficacy of chemotherapy. Ursula Matulonis: Incredibly exciting. What's the future for the drug? What are your next plans? Nicoletta Colombo: Yeah, of course. One thing I didn't say is that also the toxicity profile was quite good. And, we did not observe any increase in toxicity, even though I must say all patients receive prophylactic GCSF, but also in the comparator arm, 46% receive GCSF. So drug, well tolerated. Quality of life data very good, no, no detrimental effect. And that's why we want to do a prospective randomized phase three study. And this is planned, and we'll start at the end of the year. It's called ROSELLA. And so more than 300 patients, 360 patients will be randomized to receive Relacorilant plus Nab-Paclitaxel. Theirs is a physician choice chemo could be taxane, Nab-Paclitaxel, or liposomal doxorubicin. And the primary point will be investigator assessed progression free survival. And of course also a key secondary endpoint will be overall survival. Ursula Matulonis: Yeah. Awesome. Congratulations again. Really wonderfully conducted trial and really promising results. So thank you so much. Nicoletta Colombo: Thank you. Thank you. Thank you very much.

Related Videos

Breast Cancer

Stephanie Walker on Increasing the Participation of Black Women With Metastatic Breast Cancer in Clinical Trials

Stephanie Walker, a former nurse and current activist with the Metastatic Breast Cancer Alliance, discusses findings from the BECOME project (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement). They show that, even though Black patients comprise between 4% and 6% of all clinical trial participants, Black women with metastatic breast cancer are willing to consider taking part if steps were taken to increase their awareness, build trust through clear communication with health-care providers, involve people of shared racial/ethnic identity and health experience, and help patients find and access trials (Abstract 1014).

Breast Cancer
Immunotherapy

Erika Hamilton, MD, on Metastatic Breast Cancer: Safety Follow-up Data on T-DXd vs T-DM1

Erika Hamilton, MD, of Sarah Cannon Research Institute at Tennessee Oncology, discusses phase III data from the DESTINY-Breast03 study, which reinforced the consistent safety profile of fam-trastuzumab deruxtecan-nxki (T-DXd) vs ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer. The findings also support T-DXd’s risk benefit over that of T-DM1 (Abstract 1000).

Skin Cancer

Georgina V. Long, MD, PhD, on Melanoma: New Data on Pembrolizumab, Dabrafenib, and Trametinib

Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, The University of Sydney, discusses findings from the NeoTrio trial on neoadjuvant pembrolizumab alone, in sequence with, or concurrent with dabrafenib plus trametinib in patients with resectable BRAF-mutant stage III melanoma. The study may help clinicians determine the optimal combination of therapy (Abstract 9503).

Gynecologic Cancers

Benoit You, MD, PhD, on Ovarian Cancer: Who Benefits From Bevacizumab in the First-Line Setting

Benoit You, MD, PhD, of Lyon University hospital (HCL, France) and GINECO group (France), discusses findings from the GOG-0218 trial of patients with ovarian cancer, which appears to confirm earlier data on the link between poor tumor chemosensitivity and benefit from concurrent plus maintenance bevacizumab. In Dr. You’s validation study, patients who derived the most progression-free and overall survival benefit from bevacizumab were those with high-risk disease (stage IV or incompletely resected stage III) associated with an unfavorable KELIM score (CA-125 kinetic elimination rate constant, calculable online) (Abstract 5553).

Issues in Oncology
Global Cancer Care

Clifford A. Hudis, MD, and Karen E. Knudsen, PhD, MBA, on How ASCO and the American Cancer Society Are Collaborating to Help Patients With Cancer

Clifford A. Hudis, MD, of the American Society of Clinical Oncology, and Karen E. Knudsen, PhD, MBA, of the American Cancer Society, discuss their collaboration, pooling their research and education resources to help empower patients with cancer and their families. Within 48 hours, Drs. Hudis and Knudsen were able to gear up a rapid response to the crisis in Ukraine, forming a clinical corps of volunteers to post information online in multiple languages, which helped patients navigate their care in the war-torn region. To date, 300 European cancer organizations have joined their efforts.

Advertisement

Advertisement




Advertisement