Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer: Outcomes by Blinded Independent Central Review of the RUBY trial (ENGOT-EN6-NSGO/GOG3031/RUBY)

Background

• Dostarlimab plus carboplatin/paclitaxel led to statistically significant and clinically meaningful improvement in PFS by INV per RECIST v1.1 with an early OS trend
  • dMMR/MSI-H Population, PFS HR 0.28; 95% CI, 0.16–0.50; P<0.0001
  • Overall Population, PFS HR 0.64; 95% CI, 0.51–0.80; P<0.0001
  • Overall Population, OS HR 0.64; 95% CI, 0.46–0.87; P=0.0021a
• Both INV and BICR assessment have been shown as valid estimates of treatment effect in endometrial cancer2-6
  • Concordance between both INV and BICR can provide more confidence in results

Methods

• RUBY is a phase 3, global, randomized, double-blind, multicenter, placebo-controlled study.
• Patients (pts) with primary advanced stage III or IV or first recurrent endometrial cancer were randomized 1:1 to receive dostarlimab 500 mg, or placebo, plus carboplatin AUC 5 and paclitaxel 175 mg/m2 Q3W (6 cycles), followed by dostarlimab 1000 mg, or placebo, monotherapy Q6W for up to 3 years.
• Secondary endpoints by BICR assessment per RECIST v1.1 were PFS, ORR, DOR, and DCR in the overall and dMMR/MSI-H populations.

Results

• 494 pts were randomized (245:dostarlimab+carboplatin-paclitaxel; 249:placebo+carboplatin-paclitaxel); 47.8% had recurrent disease, 18.6% and 33.6% had primary stage III and IV disease, respectively.
• PFS by BICR was longer with dostarlimab+carboplatin-paclitaxel than placebo+carboplatin-paclitaxel in the dMMR/MSI-H (HR 0.29; 95% CI 0.158–0.543) and overall populations (HR 0.66; 95% CI 0.517–0.853).
• Consistent benefits were seen with dostarlimab+carboplatin-paclitaxel for ORR, DCR, and DOR by BICR in the dMMR/MSI-H and overall populations. Safety was previously reported.

Conclusions

• Dostarlimab + carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful PFS benefit in the overall population, with a substantial, transformative benefit in patients with dMMR/MSI-H tumors.
• PFS by BICR was consistent with PFS by INV.
• Dostarlimab + carboplatin-paclitaxel reduced the risk of progression or death by 34% in the overall population and by 71% in the dMMR/MSI-H population when assessed by BICR.
• PFS results by BICR showed high concordance with PFS by INV.
• Overall, efficacy assessments by both INV and BICR, along with a manageable safety profile, support a favorable benefit/risk profile for dostarlimab + carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer.

Powell MA, Hietanen S, Coleman RL et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer: Outcomes by Blinded Independent Central Review of the RUBY trial
(ENGOT-EN6-NSGO/GOG3031/RUBY). Abstract presented at: 2023 ASCO Annual Meeting, June 2-6, 2023.