London, UK — 16 January 2021 GlaxoSmithKline (GSK) plc announced updated data from GARNET cohort F evaluating dostarlimab in mismatch repair-deficient (dMMR) non-endometrial advanced solid cancers being presented today at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI). Study results (abstract #9) showed 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.
Dr Axel Hoos, Senior Vice President and Head of Oncology R&D, GSK said: “We are committed to finding new approaches to improve outcomes for patients with difficult to treat cancers who have limited treatment options today. These new results from the ongoing GARNET study demonstrate the potential for dostarlimab to help a broad range of patients with solid tumours that have a deficiency in DNA mismatch repair.”
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.
Dr Thierry André, Professor of Medical Oncology, Sorbonne University and Saint-Antoine Hospital in Paris said: “The patients who participated in GARNET cohort F had mismatch repair-deficient solid cancers with progressive disease on standard therapy and few available treatment options. This data shows that dostarlimab may become an important new treatment option that provides durable responses for these patients.”
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.
A Biologics License Application and Marketing Authorisation Application for dostarlimab are currently under review by the US Food and Drug Administration and the European Medicines Agency, respectively, for the treatment of patients with recurrent or advanced dMMR/microsatellite instability high (MSI-H) endometrial cancer who have progressed on or after platinum-based chemotherapy. Dostarlimab is not currently approved for use anywhere in the world.
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). GARNET is ongoing and enrolling patients.[i]
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.[ii] 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[iii] 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.
Dostarlimab was discovered by AnaptysBio and TESARO, Inc. under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody drugs that have progressed into the clinic. These are: dostarlimab (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacture of each of these products under the Agreement.
GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk Factors” in the company’s Annual Report on Form 20-F for 2019 and as set out in GSK’s “Principal risks and uncertainties” section of the Q3 Results and any impacts of the COVID-19 pandemic.
- [i] A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid Tumors (GARNET). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02715284. Accessed December 2020.
- [ii] Laken H, Kehry M, Mcneeley P, et al. Identification and characterization of TSR-042, a novel anti-human PD-1 therapeutic antibody. European Journal of Cancer. 2016;69,S102. doi:10.1016/s0959-8049(16)32902-1.
- [iii] A Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients with Recurrent or Primary Advanced Endometrial Cancer (RUBY). https://clinicaltrials.gov/ct2/show/NCT03981796. Accessed December 2020.
Posted: January 2021