Topline findings from the phase 3 SIENDO trial did not appear to likely support a supplemental new drug application use of selinexor in patients with advanced or recurrent TP53 wild-type endometrial cancer, prompting the creation of a new phase 3 trial to support a future submission.
A new placebo-controlled randomized clinical trial will assess selinexor (Xpovio) in patients with advanced or recurrent endometrial cancer and wild-type TP53 after discussions with the FDA determined that the drug’s supplemental new drug application (sNDA) was unlikely to be supported by topline findings from the phase 3 SIENDO trial (NCT03555422), according to a press release from developer Karyopharm.1
The company has plans to work with the FDA to design and launch the trial in 2022 with the intention of supporting a future sNDA. The company announced that it had received feedback from the FDA on a sNDA that included data from the phase 3 SIENDO trial, which evaluated selinexor as frontline maintenance plus chemotherapy for advanced or recurrent endometrial cancer. Notably, Karyopharm and the FDA held different opinions on the significance and benefit of study findings for the patient population. Moreover, discussions highlighted a need for further research in those with advanced or recurrent disease and wild-type TP53. Plans are in place to continue collecting and assessing data from the SIENDO trial and to collaborate with the FDA to examine regulatory pathways for patients who have wild-type TP53.
“We strongly believe in selinexor’s potential in patients with p53 wild-type [disease] and are excited to further evaluate it in this patient population to better understand its potential to address the unmet need in women with endometrial cancer,” Sharon Shacham, chief scientific officer at Karyopharm, said in a press release. “Given the significant need for new therapeutic options, we have a tremendous sense of urgency to design and enroll a new trial as quickly as possible and believe we are well-positioned to do so working with our existing SIENDO clinical trial sites.”
It is thought that data from the new upcoming trial, which will also examine patients with wild-type TP53, will read out in the first half of 2024. Findings from the SIENDO will be presented at an upcoming European Society of Medical Oncology’s Virtual Plenary and the 2022 Annual Meeting on Women’s Cancer.
“The majority of endometrial cancers are diagnosed at an early stage and are typically curable with surgery, however, women with advanced and recurrent endometrial cancer have very limited therapeutic options following frontline treatments and prognosis is typically poor,” principal investigator Ignace Vergote, MD, PhD, a gynecologist oncologist at the European Network of Gynaecological Oncological Trial and the Belgium and Luxembourg Gynaecological Oncology Group (BGOG), University of Leuven, Leuven Cancer Institute, Leuven, Belgium, stated. “Selinexor has the potential to transform the way advanced or recurrent endometrial cancer is treated in patients with p53 wild-type and I look forward to learning more from a new study.”
The SEINDO trial met its primary end point of statistically significantly improved progression-free survival (PFS), with a median PFS of 5.7 months in the selinexor arm and 3.8 months in the placebo arm (HR, 0.70; P = .0486).2 The trial included 263 patients with primary stage IV or recurrent disease who had achieved a partial or complete response after a minimum of 12 weeks of treatment with a taxane- or platinum-based chemotherapy.
Additionally, investigators reported a 37% increase in the 12-month remission rate with selinexor. Patients with wild-type TP53 had a median PFS of 13.7 months compared with 3.7 months in the placebo group, translating to a statistically significant reduction in risk of disease progression or death of 62% (HR, 0.38; P = .0006).