Dostarlimab Earns FDA Priority Review in All Advanced Endometrial Cancers

Previously, the FDA approved dostarlimab/chemotherapy for those with primary advanced or recurrent mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer in July 2023.

The FDA has granted priority review to a supplemental biologics license application (sBLA) for dostarlimab (Jemperli) plus carboplatin and paclitaxel in all adult patients with primary advanced or recurrent endometrial cancer, according to a press release from the developers, GSK.¹

The regulatory agency has set a Prescription Drug User Fee Act date of August 23, 2024, for its decision on approving dostarlimab in this expanded indication.

Previously, the FDA approved dostarlimab/chemotherapy for those with primary advanced or recurrent mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer in July 2023.² If the regulatory agency approves the sBLA, dostarlimab would also become indicated for use in patients whose tumors are mismatch repair proficient (pMMR) or microsatellite stable (MSS).

Supporting data for the sBLA came from part 1 of the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO trial (NCT03981796). Updated findings from the trial were presented at the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer.

In part 1 of the RUBY trial, dostarlimab in combination with carboplatin/paclitaxel produced a median overall survival (OS) of 44.6 months (95% CI, 32.6-not reached [NR]) compared with 28.2 months (95% CI, 22.1-35.6) in those who received placebo plus carboplatin/paclitaxel (HR, 0.69; 95% CI, 0.539-0.890).³ Among patients with dMMR or MSI-H disease, the median OS was NR (95% CI, NR-NR) vs 31.4 months (95% CI, 20.3-NR) in each respective arm (HR, 0.32; 95% CI, 0.166-0.629). Additionally, the median OS in each respective arm was 34.0 months (95% CI, 28.6-NR) vs 27.0 months (95% CI, 21.5-35.6) across the pMMR/MSS subgroup (HR, 0.79; 95% CI, 0.602-1.044).

“RUBY part 1 is the first clinical trial to show a statistically significant and clinically meaningful improvement in [OS] for an immuno-oncology therapy in combination with chemotherapy in the overall population of patients with primary advanced or recurrent endometrial cancer,” lead investigator Matthew Powell, MD, the Ira C. and Judith Gall Distinguished Professor of Obstetrics and Gynecology Washington University School of Medicine in St. Louis, said in a press release on these findings.³ “As a clinician, I celebrate the results of the RUBY part 1 trial presented today, which show how dostarlimab added to chemotherapy could potentially benefit a broader set of patients with this type of cancer.”

Investigators of the international, double-blind, phase 3 RUBY trial assessed patients with primary advanced or recurrent endometrial cancer across 2 parts. In part 1, patients were assigned to receive dostarlimab or matched placebo plus carboplatin/paclitaxel followed by dostarlimab or placebo. In part 2, investigators assessed dostarlimab plus chemotherapy followed by dostarlimab and niraparib (Zejula) compared with placebo in combination with chemotherapy.

The trial’s dual-primary end points in part 1 were progression-free survival (PFS) per investigator assessment using RECIST v1.1 criteria and OS. Investigators also conducted exploratory analyses of PFS and OS in subgroups of patients with dMMR/MSI-H or pMMR/MSS disease.

Patients 18 years and older with histologically or cytologically confirmed advanced or recurrent endometrial cancer and stage III or IV disease were eligible for enrollment on the trial.⁴ Additional eligibility criteria included having an ECOG performance status of 0 or 1 and adequate organ function.

Those who had more than 1 recurrence of endometrial cancer or prior therapy with an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent were ineligible for enrollment. Patients were also unable to enroll if they had uncontrolled central nervous system metastases, a concomitant malignancy, or unresolved adverse effects or complications following any prior major surgery.

References

1. US FDA accepts for priority review GSK’s application for an expanded indication of Jemperli (dostarlimab) plus chemotherapy to include all adult patients with primary advanced or recurrent endometrial cancer. News release. GSK. April 24, 2024. Accessed April 24, 2024. https://tinyurl.com/msvnm4pp
2. Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GSK. July 31, 2023. Accessed July 31, 2023. https://shorturl.at/izGL9
3. Positive RUBY phase III data show potential for Jemperli (dostarlimab) combinations in more patients with primary advanced or recurrent endometrial cancer. News release. GSK. March 16, 2024. Accessed April 24, 2024. https://tinyurl.com/bduurwmp
4. A study to evaluate dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in participants with recurrent or primary advanced endometrial cancer (RUBY). ClinicalTrials.gov. Accessed April 24, 2024. https://tinyurl.com/2bphnvpv