Welcome to the 2021 IGCS Meeting Program Scheduling

Objectives

EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 is an open-label, randomized (1:1), multi-center, Phase 3 trial of cemiplimab vs investigator’s choice (IC) chemotherapy (chemo) in recurrent/metastatic (R/M) cervical cancer that has progressed after first-line (1L) platinum-based treatment (tx).

Methods

Patients (pts) were enrolled regardless of PD-L1 expression; received cemiplimab 350 mg IV Q3W or IC chemo (pemetrexed, vinorelbine, gemcitabine, irinotecan, or topotecan), up to 96 weeks; and were stratified by histology (squamous cell carcinoma [SCC] / adenocarcinoma or adenosquamous [AC]). Primary endpoint was OS, analyzed hierarchically in pts with SCC followed by total population (SCC + AC). Additional endpoints included PFS, ORR, QoL, and safety. Interim analysis was scheduled when 85% events occurred among SCC pts.

Results

608 pts were randomized: median age, 51 years (range, 22‒87); 477 SCC, 131 AC; ECOG performance status: 0 (46.5%), 1 (53.5%). Median cemiplimab exposure was 15 weeks (range, 1.4‒100.7). At interim analysis, OS (Table), PFS, ORR in overall and SCC populations, and mean change from baseline QoL in SCC, favored cemiplimab. Most common tx emergent AEs of any grade for cemiplimab vs IC chemo were anemia (25% vs 45%), nausea (18% vs 33%), and vomiting (16% vs 23%). Discontinuation due to AEs occurred in 8% (cemiplimab) and 5% (IC chemo).

Conclusions

Cemiplimab significantly improves OS over single agent chemo for pts with R/M cervical cancer after 1L platinum-based tx regardless of histology and despite not having been selected by PD-L1 status. No new safety signals were observed.

Objectives

In Study 309/KEYNOTE-775, lenvatinib + pembrolizumab (LEN+pembro) significantly improved PFS, OS, and ORR versus treatment of physician’s choice (TPC) in aEC patients with DNA mismatch repair proficient tumors and all-comers following platinum-based therapy. We report results for dMMR aEC patients.

Methods

Patients in Study 309/KEYNOTE-775 were randomized 1:1 to lenvatinib 20 mg orally daily + pembrolizumab 200 mg IV Q3W or TPC (doxorubicin 60 mg/m² IV Q3W or paclitaxel 80 mg/m² IV QW [3 weeks on/1 week off]). Patients had aEC with 1 prior platinum-based chemotherapy regimen (2 if one was given in the neoadjuvant/adjuvant setting). Prespecified efficacy (PFS, OS, and ORR) and safety analyses among dMMR patients are reported. P-values are nominal. Tumors were assessed by blinded independent central review per RECIST v1.1.

Results

130 Patients with dMMR aEC were randomized to LEN+pembro (n=65) or TPC (n=65). Median follow-up was 13.5 months for the LEN+pembro group and 8.8 months for the TPC group (data cutoff: October 26, 2020). PFS (median 10.7 vs 3.7 months) and OS (median not reached vs 8.6 months) were longer with LEN+pembro vs TPC. ORR was greater with LEN+pembro (40.0%) vs TPC (12.3%). Additional results are in the Table. Grade ≥3 treatment-emergent adverse events occurred in 95% and 73% of patients in the LEN+pembro and TPC groups, respectively.

Conclusions

LEN+pembro improved PFS, OS, and ORR vs TPC in patients with dMMR aEC, with a manageable safety profile generally consistent with all-comers and previous studies.

Objectives

Dostarlimab is a humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interactions with PD-1 ligands. GARNET is a phase 1 study assessing antitumor activity and safety of dostarlimab monotherapy in patients with advanced solid tumors.

Methods

This multicenter, open-label, single-arm study is conducted in 2 parts: dose escalation and expansion. Patients with advanced or recurrent mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer (EC) or mismatch repair–proficient (MMRp) EC that progressed on or after a platinum regimen received dostarlimab 500 mg intravenously Q3W for 4 cycles, then 1000 mg Q6W until disease progression or discontinuation. Primary endpoints were objective response rate (ORR) and duration of response by BICR using RECIST v1.1. Here we report ORR in dMMR/MSI-H and MMRp EC by prior lines of therapy (LOTs).

Results

Efficacy analyses included 108 dMMR/MSI-H and 142 MMRp patients. ORR was 43.5% in dMMR/MSI-H and 13.4% in MMRp. ORR was slightly higher (47.8%) in patients with dMMR/MSI-H with 1 prior LOT but lower (35.9%) in those who received ≥2 prior LOTs. In the MMRp population, ORR was similar, regardless of prior LOTs.

Safety has been previously reported.¹

Conclusions

Dostarlimab demonstrated antitumor activity in recurrent or advanced dMMR/MSI-H and MMRp EC regardless of number of prior LOTs. Patients with dMMR/MSI-H EC who received 1 prior LOT had slightly higher ORR than those who received ≥2 prior LOTs.

1. Oaknin A, et al. Ann Oncol 2020;31(suppl 4):S1142–S1215.