GSK plc...announced the European Commission (EC) has granted marketing authorisation for Jemperli (dostarlimab) in combination with carboplatin-paclitaxel (chemotherapy), for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy.

The Medicines and Healthcare products Regulatory Agency (MHRA) has today (2 October 2023) authorised a new indication for Jemperli (dostarlimab), a treatment for some types of endometrial cancer in adults...It can be used to treat patients that have a tumor abnormality called mismatch repair deficient (dMMR) / microsatellite instability-high (MSI-H) when the cancer is at an advanced stage when first diagnosed or has returned after previous treatment.

GSK plc...announced that the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab) in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H).

JEMPERLI is a programmed death receptor-1 (PD-1)–blocking antibody indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation.

AnaptysBio, Inc...today announced that the European Commission has granted conditional marketing authorization for JEMPERLI (dostarlimab) for use in women with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer who have progressed on or following prior treatment with a platinum containing regimen.

Dostarlimab-gxly is indicated for patients with dMMR recurrent or advanced endometrial carcinoma that has progressed on or following prior treatment with a platinum-containing regimen.

GSK plc...announced positive headline results from a planned analysis of Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial investigating Jemperli (dostarlimab) plus standard-of-care chemotherapy (carboplatin and paclitaxel), followed by dostarlimab as a single agent, compared to placebo plus chemotherapy followed by placebo in adult patients with primary advanced or recurrent endometrial cancer. The trial met its primary endpoint of overall survival (OS), demonstrating a statistically significant and clinically meaningful benefit in the overall patient population.

GSK plc...announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of Jemperli (dostarlimab) in combination with carboplatin-paclitaxel (chemotherapy), for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy...GSK’s application for the authorisation of dostarlimab is based on interim analysis results from Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial...

Patients (pts) with primary advanced stage III or IV or first recurrent EC were randomized 1:1 to receive dostarlimab 500 mg, or PBO, plus carboplatin AUC 5 and paclitaxel 175 mg/m2...PFS by BICR was longer with dostarlimab+CP than PBO+CP 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...Dostarlimab+CP showed clinically meaningful improvement in BICR-assessed PFS in the dMMR/MSI-H and overall populations compared with CP alone.

Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population.

GSK...announced interim results from Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial investigating Jemperli (dostarlimab) plus standard-of-care chemotherapy (carboplatin-paclitaxel) followed by dostarlimab compared to chemotherapy plus placebo followed by placebo in adult patients with primary advanced or recurrent endometrial cancer....A statistically significant and clinically meaningful improvement in progression free survival (PFS) was observed for dostarlimab plus carboplatin-paclitaxel in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) population (n=118) and in the overall population (n=494) versus placebo plus chemotherapy.

GSK plc...announced positive headline results from the planned interim analysis of Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial investigating Jemperli (dostarlimab) plus standard-of-care chemotherapy (carboplatin-paclitaxel) followed by Jemperli compared to chemotherapy plus placebo followed by placebo in adult patients with primary advanced or recurrent endometrial cancer...The trial met its primary endpoint of investigator-assessed progression-free survival (PFS). It showed a statistically significant and clinically meaningful benefit in the prespecified mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) patient subgroup and in the overall population.

...Patient has evidence of tumor DNA damage repair dysfunction (dMMR/MSI-H) via locally available, validated methodology....

...All histologic subtypes of endometrial adenocarcinoma could be included if MMRd/MSI-H 9....

...Cohort A1 (dMMR/MSI-H endometrial cancer) and Cohort A2 (MMR-proficient/MSS endometrial cancer)...

...- MMR-D or MSI-H (submission of report[s] required for....

...All histologic subtypes of endometrial adenocarcinoma could be included if MMRd/MSI-H,7. ...

Dostarlimab demonstrated durable antitumor activity and safety in patients with dMMR/MSI-H EC. Biomarkers associated with EC may identify patients likely to respond to dostarlimab.

In this adjusted indirect dataset, patients with recurrent/advanced mismatch repair deficient/microsatellite instability-high endometrial cancer post-platinum-based chemotherapy who received dostarlimab in the GARNET trial had significantly improved overall survival compared with patients receiving current second-line treatment in England.

Initial results from the Korean EAP of dostarlimab monotherapy treatment for patients with recurrent or advanced dMMR/MSI-H EC demonstrated encouraging antitumor activity with no new safety signals, further supporting dostarlimab use in Korean patients.

PFS and OS results favored the D+CP arm in the dMMR/MSI-H, TP53mut, and NSMP subgroups, with the largest benefit observed in the dMMR and TP53mut groups...Dostarlimab+CP is associated with improved PFS and OS in the dMMR/MSI-H, NSMP, and TP53 subgroups and adds prognostic value in pA/rEC.

Dostarlimab+CP significantly improved PFS while maintaining QoL, further supporting its use as a standard of care in pts with dMMR/MSI-H pA/rEC.

We report on PFS and OS in pts with dMMR solid tumors from 2 expansion cohorts of the GARNET trial….Dostarlimab demonstrated durable antitumor activity and favorable PFS and OS in dMMR solid tumors, including EC, gastrointestinal, and other tumor types.

This study compared survival outcomes of pts with A/R mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) EC receiving dostarlimab...Median TTD (months, 95% CI) was longer for pts treated with dostarlimab across all matching scenarios (SC1: 7.8 [4.1, not estimable (NE)]; SC2: 9.7 [5.5, NE]; SC3: 14.0 [6.4, 17.9]) than the overall RW cohort (3.4 [3.2, 3.4])....Results suggest that pts in GARNET with dMMR/MSI-H A/R EC receiving dostarlimab had better OS and longer TTD compared with pts receiving current 2L tx in England.

GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or cohort A2 (MMRp/MSS EC) based on local assessment....ORRs were 45.5% (dMMR/MSI-H) and 15.4% (MMRp/MSS; Table)….Probability of PFS at 6, 9, and 12 mo was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 35.8%, 31.3%, and 29.4% in MMRp/MSS EC, respectively….Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with better outcomes: a higher response rate and longer PFS and OS.

For this third interim analysis, 153 pts with dMMR/MSI-H EC and 210 pts with dMMR/MSI-H/POLε-mut non-EC solid tumors (56% colorectal cancer, 11% gastric) were enrolled and treated. Efficacy analysis was performed for 143 dMMR/MSI-H EC and 204 dMMR/MSI-H/POLε-mut non-EC pts who had measurable disease at baseline and ≥6 mo of follow-up. ORRs were 45.5% (dMMR/MSI-H EC) and 43.1% (dMMR/POLε-mut non-EC solid tumors; Table). Probability of PFS at 6, 9, and 12 mo was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 51.8%, 48.1%, and 46.4% in dMMR/MSI-H/POLε-mut non-EC. Median (m) DOR and mOS were not reached for either cohort. Dostarlimab demonstrated durable antitumor activity across 16 tumor types in pts with dMMR solid tumors...

Two cohorts of patients with EC were recruited: those with dMMR/ MSI-H disease (cohort A1) and those with proficient/ stable (MMRp/MSS) disease (cohort A2)….In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses....Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile.

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...ORR was 43.5% in dMMR/MSI-H...Dostarlimab demonstrated antitumor activity in recurrent or advanced dMMR/MSI-H...

Cohort A1 enrolled patients with advanced or recurrent dMMR/MSI-H endometrial cancer (EC)...Dostarlimab demonstrated durable antitumor activity in patients with dMMR solid tumors, with consistent antitumor activity seen across endometrial and non endometrial tumor types. The safety profile was manageable, with no new safety signals detected.

GlaxoSmithKline (GSK) plc today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending dostarlimab, an anti-programmed death-1 (PD-1) monoclonal antibody, for use as monotherapy in women with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer...The application is based on data from the GARNET study, which represents the largest dataset of an anti-PD-1 monotherapy treatment in endometrial cancer.

Pts with recurrent or advanced dMMR/MSI-H EC that progressed on a platinum regimen received 500 mg Q3W*4 of dostarlimab...PROs from the GARNET trial showed that dostarlimab was generally well tolerated and disease-related symptoms were improved or maintained while on treatment. These data, along with the efficacy and safety profile of dostarlimab, support use of dostarlimab in pts with dMMR/MSI-H advanced EC.

dostarlimab was associated with clinically meaningful and durable antitumor activity with an acceptable safety profile for patients with deficient mismatch mutation repair endometrial cancers...

dMMR ORR was 44.7%; MMRp ORR was 13.4%....Dostarlimab demonstrated durable antitumor activity in both dMMR and MMRp advanced/recurrent EC. dMMR status by IHC was associated with a higher response rate…

PROs from the GARNET trial showed that dostarlimab was generally well tolerated and disease-related symptoms were improved or maintained while on treatment. These data, along with the efficacy and safety profile of dostarlimab, support use of dostarlimab in pts with dMMR/MSI-H advanced EC

Preliminary data for dostarlimab demonstrated clinical activity in patients with previously treated recurrent or advanced MMR-deficient endometrial cancer with an acceptable safety profile.