The mix of two well-known immunotherapy brokers, nivolumab (Opdivo) and ipilimumab (Yervoy), produced responses with a well-known security profile in sufferers with clear cell carcinomas of the ovary and different websites, based on Don Dizon, MD.
The ultimate readout of the part 2 BrUOG 354 trial (NCT03355976), which had a median follow-up of 11.3 months (vary, 1.6-46.4), revealed that sufferers with extra-renal clear cell cancers who acquired nivolumab plus ipilimumab (n = 30) achieved an general response charge (ORR) of 33.3%, which included an entire response (CR) charge of 16.7%.1 These respective charges have been 14.3% and 0% amongst sufferers who acquired nivolumab alone (n = 14).
“This represents a therapy possibility that ought to be extra extensively accessible,” Dizon, who’s the director of ladies’s cancers at Lifespan Most cancers Institute and an assistant professor of medication at The Warren Alpert Medical College of Brown College, each in Windfall, Rhode Island, mentioned in an interview with OncLive® throughout the 2024 ASCO Annual Assembly.
Within the interview, Dizon mentioned key up to date findings from BrUOG 354, the potential way forward for immunotherapy for sufferers with ovarian and different gynecologic cancers, and the ability of decentralized scientific trials.
OncLive: What was the rationale for the BrUOG 354 trial?
Dizon: When you consider ovarian most cancers, there are completely different sorts of histologies. One of many extra worrisome varieties is obvious cell most cancers. Clear cell histologies happen within the ovary roughly 10% of the time, within the uterus roughly 6% of the time, and within the cervix roughly 5% of the time. These are uncommon tumors that [present] throughout gynecologic websites however can occur wherever exterior of the kidney, as effectively.
The difficulty is that these clear cell cancers, particularly of the gynecological tract, are additionally way more aggressive. They don’t have a tendency to reply effectively to chemotherapy, and once they relapse or turn into metastatic, the prognosis is poorer in contrast with that of serous carcinomas. There’s an actual want for progressive therapies.
The rationale for this particular trial of immunotherapy comes from anecdotal reviews of CRs when individuals acquired immunotherapy on bigger ovarian most cancers trials. This has been persistently seen, nevertheless, the numbers of individuals enrolled in these trials have been small, a mean of lower than 20 individuals. We devised BrUOG 354 to offer extra of a definitive reply to the query: How effectively does immunotherapy work in individuals with clear cell cancers?
What affected person inhabitants was enrolled on this examine?
We enrolled individuals with ovarian or extra-renal clear cell cancers. The intent, once we began this trial, was [to enroll] anybody who was identified with a transparent cell most cancers—whether or not it was [in] the abdomen, colon, rectum, or wherever [else]. In the end, we enrolled individuals with gynecological cancers. We had a cohort of individuals with ovarian most cancers and a small proportion of individuals with uterine or different extra-renal websites. One particular person had illness, for instance, within the belly wall. That was their presentation, and we assumed it was on account of endometriosis-associated clear cell most cancers.
What key findings have been beforehand offered from the examine?
This examine was offered [in 2022,] once we did the interim evaluation. On the first stage, we enrolled 13 individuals [to receive] therapy with nivolumab [and 15 people to receive the] mixture of nivolumab and ipilimumab. After we enrolled these individuals in each arms, we stopped the examine and appeared to see the place we have been.
We needed to proceed enrollment provided that it made sense. If it appeared that the response charges have been low, we weren’t planning to proceed to review. Nonetheless, if there was a touch that this [combination] may very well be good, we’d proceed. At that time, we closed the arm for nivolumab, due to these 13 [people enrolled], 2 individuals had a partial response, nobody had a CR, and the ORR was 15.4%. At ASCO this yr, [I presented findings from] the ultimate evaluation after the complete examine was accomplished.
What have been the efficacy findings from the ultimate evaluation?
The attention-grabbing findings is that [with] the mix of nivolumab and ipilimumab, you get the next response charge, of 33.3%. That included 5 individuals who had a CR, which is unparalleled in [people with] clear cell carcinoma who’ve seen prior chemotherapy and [have] superior or metastatic [disease]. We additionally reported that the median progression-free survival was 2.2 months with nivolumab and 5.6 months with the mix. The median general survival was 17.3 months with nivolumab and 24.7 months with the mix. Importantly, individuals who responded to the mix had a sturdy response. We had individuals staying on the examine as they approached the 2-year mark, and even at this time, persons are persevering with on therapy.
What have been the up to date security findings?
Encouragingly, therapy with immunotherapy on this group of individuals was not related to any new security alerts. The antagonistic impact [AE] profile was per what we all know can occur and the AE profile of immunotherapy typically.
What are the scientific implications of those findings?
It’s going to be troublesome to check that we’re going to have a randomized trial of, say, standard-of-care chemotherapy vs immunotherapy. That may be best, as a result of then we will definitively reply how effectively, in contrast with normal therapy, nivolumab and ipilimumab work, maybe in a extra tailor-made inhabitants of individuals with ovarian clear cell carcinoma. Nonetheless, I don’t assume we’re going to get there, as a result of it took me roughly 5 years to enroll 44 individuals.
What I do assume is that immunotherapy is [a treatment] that oncologists the world over are snug with. We’ve heard about its use in different settings, and for essentially the most half, quite a lot of us have expertise with these medication. This dataset signifies that [nivolumab plus ipilimumab] is a crucial therapy possibility for individuals who have a really high-risk histology for ovarian, uterine, and even cervical most cancers.
Is there anything that you simply wish to add concerning the examine?
This was a collaboration between 3 establishments in Illinois, in addition to 1 establishment in Windfall, Rhode Island. We enrolled throughout the COVID-19 pandemic. We didn’t cease enrollment, and we didn’t cease anybody from being handled. Nonetheless, a lesson discovered from the pandemic is that you are able to do a therapeutic trial in a decentralized manner. What meaning for us is that we saved individuals on trial and prevented them from getting on a airplane throughout the top of the pandemic by permitting shipments of examine medication for supply near dwelling. They stayed on trial. All of the regulatory follow-up was executed centrally utilizing telehealth, for instance. Nonetheless, it is a proof of idea that we will decentralize a therapeutic trial—particularly when the medication are acquainted.
What ongoing analysis on this space are you trying ahead to seeing?
There are 2 issues which are going to be necessary. One is to attempt to see whether or not we will discover predictive biomarkers that monitor with response or lack of response to immune checkpoint inhibitors and immunotherapy typically. We’re doing that evaluation now to see whether or not we will discover any biologic correlates.
The second is to assume ahead. If we presume that immunotherapy can be one thing that folks with clear cell entry, we’re going to wish to strive to determine what else might be executed. Persevering with to discover choices within the frontline setting, that first therapy paradigm for recurrent or metastatic illness, continues to be necessary. Nonetheless, we’re going to see a bigger proportion of sufferers who’ve acquired immunotherapy. What can we provide them within the immunotherapy-exposed setting?
I’ve simply talked about how the exercise of immunotherapy in clear cell cancers is necessary. As you scan a wider lens, it’s doubtless that on the heels of the [phase 3] AGO-OVAR 2.29 trial [NCT03353831] of atezolizumab [Tecentriq] in platinum-resistant ovarian most cancers, we’re prone to abandon an method the place single-agent immunotherapy is evaluated for efficacy in ovarian most cancers as a result of it’s unlikely it has a job to play in ovary most cancers particularly.
Disclosures: Dr Dizon reviews consulting roles with Glaxo SmithKline, Clovis/Pharma&, AstraZeneca, Pfizer, and Kronos Biotech; in addition to possession of inventory choices from Doximity and Midi.
Reference
Dizon DS, Mathews CA, David SM, et al. Remaining outcomes of BrUOG 354: a randomized part II trial of nivolumab alone or together with ipilimumab for individuals with ovarian and different extra-renal clear cell carcinomas. J Clin Oncol. 2024;42(suppl 17):LBA5500. doi:10.1200/JCO.2024.42.17_suppl.LBA5500
