The European Commission has granted conditional marketing authorization to dostarlimab for the treatment of patients with microsatellite instability–high/mismatch repair deficient recurrent or advanced endometrial cancer who have progressed on or following prior therapy with a platinum-containing regimen.
The European Commission has granted conditional marketing authorization to dostarlimab (Jemperli) for the treatment of patients with microsatellite instability–high (MSI-H)/mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer who have progressed on or following prior therapy with a platinum-containing regimen.1
The decision is based on findings from the ongoing, multi-cohort GARNET trial (NCT02715284), in which dostarlimab led to an objective response rate (ORR) of 43.5% (95% CI, 34%-53.4%) and a disease control rate (DCR) of 55.6% (95% CI, 45.7%-65.1%) in a cohort of patients with recurrent or advanced dMMR/MSI-H endometrial cancer who progressed on or post-platinum-containing chemotherapy (n = 108 evaluable for efficacy).
The approval marks dostarlimab as the first PD-1 inhibitor indicated in endometrial cancer in Europe, noted GlaxoSmithKline, the developer of dostarlimab.
“As we saw in the pivotal GARNET trial that supported this approval, treatment with dostarlimab has the potential to provide clinically significant and durable responses in patients who formerly had few treatment options,” said primary GARNET investigator Ana Oaknin, MD, head of the Gynaecologic Cancer Program at Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, in Barcelona, Spain. “This approval represents a step forward, providing a new treatment for women with recurrent or advanced dMMR/MSI-H endometrial cancer who have previously failed a platinum-based chemotherapy.”
In GARNET, investigators tested single-agent dostarlimab in expansion cohorts across multiple tumor types. Patients who were eligible for enrollment were treated with dostarlimab at 500 mg of intravenous (IV) every 3 weeks for 4 cycles followed by 1000 mg IV every 6 weeks until disease progression.
The study consists of dose-finding (part 1), fixed-dose safety run-in (part 2A), and expansion cohorts (part 2B). The expansion cohort included 5 groups: dMMR endometrial cancer (A1; n = 129), MMRp endometrial cancer (A2; n = 161), non–small cell lung cancer (E), nonendometrial dMMR/MSI-H cancer (F), and platinum-resistant ovarian cancer (G).
The coprimary end points are ORR and DOR by BICR RECIST v1.1 criteria. Additionally, immune-related RECIST criteria served as a prespecified secondary end point, due to standard RECIST criteria potentially undervaluing the clinical benefit of immunotherapy.
Eligibility criteria in cohorts A1 and A2 included disease progression on or after platinum-doublet therapy, have received 2 or fewer prior lines of therapy for recurrent or advanced disease, and have measurable disease at baseline. Additionally, patients had to have PD-L1–naïve disease and confirmed MMR/MSI disease by MMR immunohistochemistry (IHC) results.
Additional findings in GARNET used as the basis for the approval included median duration of response (DOR) data, which was not reached with dostarlimab (2.6 to 28.1+ months). The DOR at 6 months was 97.9% (95% CI, 85.8%-99.7%); at 1 year, it was 90.9% (95% CI, 73.7%-97.1%).
Overall, the safety profile for patients in cohort A1 was comparable with the overall study population. A total 129 patients were evaluable for safety from cohort A1. Here, the most common adverse events (≥10%) were anemia (25.6%), nausea (25.0%), diarrhea (22.5%), vomiting (18.4%), arthralgia (13.8%), pruritus (11.5%), rash (11.1%), pyrexia (10.5%), and hypothyroidism (10.1%). The discontinuation rate due to AEs was 3.3% (n = 17), most of which were immune related.
Serious AEs were reported in 8.7% of patients, the majority of which were also immune-related AEs.
“Today’s approval of dostarlimab offers a new treatment option for women with recurrent or advanced dMMR/MSI-H endometrial cancer,” said Icó Tóth, co-chair of European Network of Gynaecological Cancer Advocacy Groups, council member for European Society of Gynaecological Oncology, president, Mallow Flower Foundation, in Hungary. “We’re inspired by the efforts of companies like GSK who are continuing to innovate for patients in dire need of new options.”
On April 22, 2021, the FDA granted an accelerated approval to dostarlimab for the treatment of patients with recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing chemotherapy and whose cancers are mismatch dMMR, which is determined by an FDA-approved test.2
Dostarlimab is also being investigated in earlier lines of therapy for patients with endometrial cancer, as well as in combination with other agents in advanced solid tumors.