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

2022 ASCO Annual Meeting


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).


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

Nancy Davidson, MD: In It for the Long Haul: Outcomes in Hormone Receptor–Positive Breast Cancer

Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, reviews results from four abstracts about the importance of long-term follow-up in studies of adjuvant endocrine therapy for hormone receptor–positive breast cancer. Because the natural history of hormone receptor–positive breast cancer is long, an effort is underway to improve selection of patients by clinical parameters or biomarkers, refine the endocrine therapy background, and administer more effective combinations of endocrine therapy with other agents.


Courtney D. DiNardo, MD, MSCE, and Stéphane de Botton, MD, PhD, on AML: New Data on IDH2-Mutant Alleles, Enasidenib, and Conventional Care

Courtney D. DiNardo, MD, MSCE, of The University of Texas MD Anderson Cancer Center, and Stéphane de Botton, MD, PhD, of Institut Gustave Roussy, discuss phase III findings from the IDHENTIFY trial, which showed that mutational burden and co-mutational profiles differed between patients with relapsed or refractory acute myeloid leukemia that exhibited IDH2-R140 and IDH2-R172 mutations. Enasidenib improved survival outcomes for patients with IDH2-R172 mutations: median overall survival and 1-year survival rates were approximately double those in the conventional care arm (Abstract 7005).

Lung Cancer

Maxwell Oluwole Akanbi, MD, PhD, on Lung Cancer: The Effect of Screening on the Incidence of Advanced Disease

Maxwell Oluwole Akanbi, MD, PhD, of McLaren Regional Medical Center, discusses the study he conducted, using the SEER database, to evaluate the impact of lung cancer screening recommendations on low-dose CT scanning. The data suggest that guidelines from the U.S. Preventive Services Task Force led to a more rapid decline in the incidence of advanced disease in the United States, especially among minority populations (Abstract 10506).

Colorectal Cancer

Michael J. Overman, MD, and Jeanne Tie, MBChB, MD, on Colon Cancer: Guiding Adjuvant Chemotherapy With ctDNA

Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, and Jeanne Tie, MBChB, MD, of Peter MacCallum Cancer Centre, discuss results from the DYNAMIC trial, in which a circulating tumor DNA (ctDNA)-guided approach reduced the use of adjuvant chemotherapy without compromising recurrence-free survival in patients with stage II colon cancer (Abstract LBA100).

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).