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Efficacy data of Dostarlimab, a PD-1 inhibitor, in mismatch repair-deficient solid cancers


Updated data from GARNET cohort F evaluating Dostarlimab in mismatch repair-deficient ( dMMR ) non-endometrial advanced solid cancers were presented at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium ( ASCO GI ).
Study results have shown a 38.7% objective response rate ( ORR ) ( n=106, 95% CI; 29.4–48.6 ) in patients with dMMR advanced solid cancers who received Dostarlimab, an investigational anti-programmed death-1 ( PD-1 ) monoclonal antibody.
Additionally, after a median follow-up of 12.4 months, the median duration of response ( DoR ) had not yet been reached, and responses were durable across tumour types.

Cohort F of the GARNET trial enrolled patients with dMMR non-endometrial solid cancers, the majority of which were gastrointestinal, with highest prevalence in colorectal, gastric and small intestinal cancers among other solid cancers of which the majority of patients ( n=81 ) had been treated with 2 or more prior lines of systemic therapy.
Patients received 500 mg of Dostarlimab every three weeks for four doses and 1,000 mg of Dostarlimab every six weeks thereafter for up to two years, or until disease progression or discontinuation.
The primary objectives of the study were confirmed ORR and DoR, as assessed against RECIST v 1.1 by blinded independent central review.

Objective response rates were consistent across patients with colorectal ( n=69 ) and non-colorectal cancers ( n=37 ), including small intestine, gastric, pancreatic, ovarian, liver and other types of solid cancers.
In patients with colorectal cancer, the ORR was 36.2% ( 95% CI; 25.0–48.7 ) and in patients with non-colorectal cancer the ORR was 43.2% ( 95% CI; 27.1–60.5 ).
8% of patients in cohort F achieved a complete response.

Dostarlimab was well tolerated with a low discontinuation rate ( 3.5% ) due to treatment-related adverse events ( TRAEs ) among patients who received one or more doses of Dostarlimab and were evaluable for safety ( n=144 ).
The most commonly reported TRAEs were asthenia ( 13% ), diarrhoea ( 13% ), pruritis ( 13% ), arthralgia ( 9% ), and fatigue ( 9% ).
Grade 3 or greater TRAEs occurred in 8% of patients.
No deaths associated with dostarlimab were reported in the study.

The ongoing phase I GARNET trial is evaluating Dostarlimab as monotherapy in patients with advanced solid tumours.
Part 2B of the study includes five expansion cohorts: dMMR/MSI-H endometrial cancer ( cohort A1 ), mismatch repair proficient / microsatellite stable ( MMRp/MSS ) endometrial cancer ( cohort A2 ), non-small cell lung cancer ( cohort E ), dMMR/MSI-H non-endometrial cancer or POLE-mut solid tumour basket cohort ( cohort F ), and Platinum-resistant ovarian cancer without BRCA mutations ( cohort G ).

Dostarlimab is a humanised PD-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.
In addition to GARNET, Dostarlimab is being investigated in other registrational enabling studies, including the phase 3 RUBY study for patients with recurrent or primary advanced endometrial cancer in combination with standard of care ( SOC ) chemotherapy and the phase 3 FIRST study of Platinum-based therapy with Dostarlimab and Niraparib versus SOC Platinum-based therapy as first-line treatment of stage III or IV non-mucinous epithelial ovarian cancer.
Dostarlimab is also being evaluated in combination with other therapeutic agents for patients with advanced solid tumours or metastatic cancer. ( Xagena )

Source: ASCO Gastrointestinal Cancers Symposium, 2021

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