MADRID, Spain—Clovis Oncology may be the middle child in the new wave of ovarian cancer treatments, but it’s hoping some new data will take it to the head of the PARP class.
On Friday, the U.S.-based biotech rolled out details of its Ariel-3 study, which tested its drug Rubraca (rucaparib) in 564 patients who had completed platinum chemo, as a tool for holding off a cancer recurrence. As expected, the med stalled cancer growth for more than a year, at the median, in patients with a BRCA mutation; the PARP drugs perform best in those patients, and rival meds have performed similarly in their own trials.
But importantly, patients with “wild-type” BRCA—without the mutation, or 354 of the women in the study—also benefited, winning up to 11.1 months of progression-free time, with the best results among women whose tumors test positive for loss of heterozygosity. Those tumors behave similarly to BRCA-mutated disease. The survival numbers came from an independent analysis of the trial data.
And among all comers, the median progression-free survival time was 13.7 months, a result that has Clovis CEO Patrick Mahaffey hopeful about an expanded FDA approval for his drug.
“We achieved a significant and substantial benefit across all the populations we studied," Mahaffey said ahead of the data release at the European Society of Medical Oncology (ESMO) meeting in Madrid. And that's in a “broad population” of all comers.
Even better for some women, Mahaffey said, is the fact that a number of patients in the study not only enjoyed a longer period before their disease progressed, but also saw residual tumors shrink—some of them completely.
Together, those data set Rubraca apart from its PARP fellows, Mahaffey said; the data are “better than anybody has seen” in the field.
Ariel-3, unlike some other PARP studies, didn’t only enroll patients who’d responded completely to platinum chemo. Two-thirds of the patients in the trial had only achieved a partial response to chemo, and so investigators could monitor residual tumors, to see whether Rubraca could improve the initial response—and it did. Among BRCA-positive patients, 38% showed a treatment response, and 18% saw their residual tumor disappear, Mahaffey said.
“What we see with Rubraca is a much more pronounced benefit,” he said ahead of the data release. “The drug didn’t just maintain the original response, but we can improve on that original response. Women are acutely aware of the risk and, sadly, the likelihood that the tumor will re-remerge. To be able to tell a patient, you have less tumor now than when you thought you had achieved a benefit from platinum chemotherapy—that is extraordinary.”
Based on the Ariel 3 data, Clovis plans to file for FDA approval in the maintenance setting—and in patients regardless of BRCA status. That’s a nod Tesaro’s Zejula won in March and first-to-market Lynparza, now shared by AstraZeneca and Merck & Co., just picked up in August. Rubraca is for now limited to patients who have failed two rounds of previous treatment. An FDA decision would be due in six months, but it could arrive more quickly, if the timing of Lynparza’s new approval is any guide.
With that nod, Clovis would be on even footing with those two meds, and it’s hoping the new data can give it an edge when carving out its share of the market. And so far, the PARP competition has been fierce: After Tesaro nabbed its approval for Zejula, the med started grabbing share; in early August, Tesaro CEO Lonnie Moulder said the new product held a 60% piece of the PARP pie at the end of the second quarter.
Lynparza is now looking to claw some of that back, of course. When the drug won its expanded approval last month, Evercore ISI analyst Steven Breazzano called it an “incremental negative” for Clovis (at least for now, because it can’t yet compete in that setting) and Tesaro (because it no longer has that setting to itself).
When the time comes, Mahaffey figures Rubraca’s data “speak for themselves in terms of efficacy and tolerability,” and the PARP field will only grow. “We and others will explore and have proven to some extent already the utility of this class of compounds in multiple tumor types, so it’s not limited to these indications,” Mahaffey said, giving PARPs plenty of room to expand.
To that end, Clovis is putting the med through a range of follow-up studies as well. Clovis has two registrational studies going in prostate cancer, and it recently inked a deal with Bristol-Myers Squibb to study Rubraca in combination with PD-1 med Opdivo in first-line ovarian cancer, triple-negative breast cancer and castration-resistant prostate cancer. Merck and AstraZeneca's $8.5 billion deal on Lynparza also includes combo trials with Keytruda, the former's PD-1 checkpoint inhibitor.
“The world is competitive,” Mahaffey said. “The fact that there are only three PARP inhibitors now is rare—there are 55 PD-1/PD-L1 drugs in clinical development, 15 of which are in phase 3. … Here, it’s still three drugs in a class looking at patients across multiple tumor types. While I’m confident Rubraca has the potential to stand alone and above, I also know there’s room for more than one.”