GSK Announces Promising Phase II Results of Dostarlimab as Neoadjuvant Therapy in dMMR Locally Advanced Rectal Cancer at 2022 ASCO

Surgical resection of the rectum after neoadjuvant chemotherapy and radiation is the standard treatment for locally advanced rectal cancer. Deficiency in DNA mismatch repair (dMMR) is one of the leading causes of rectal cancer. At the 2022 ASCO Annual Meeting, GSK reported the results of a prospective Phase II study on the use of its PD-1 antibody dostarlimab in treating patients with dMMR-deficient Stage II or III rectal adenocarcinoma.

Subjects received dostarlimab treatment once every 3 weeks for 6 months. Afterward, patients will undergo standard chemoradiotherapy and surgical treatment. However, patients who achieve a clinical complete response will no longer receive chemoradiotherapy or surgery. The primary endpoint of this study is the sustained clinical complete response at 12 months after completing dostarlimab treatment or the pathological complete response after completing dostarlimab treatment with or without chemoradiotherapy, as well as the overall response after neoadjuvant dostarlimab treatment with or without chemoradiotherapy.

The results showed that a total of 12 patients completed dostarlimab treatment and received at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74-100) achieved clinical complete remission, with no evidence of tumors found on magnetic resonance imaging, 18F-fluorodeoxyglucose-positron emission tomography, endoscopic evaluation, digital rectal examination, or biopsy.

At the time of this report, no patients had received chemoradiotherapy or surgery, and no progression or recurrence was reported during the follow-up period (6-25 months). No grade 3 or higher adverse events were reported. The study results have also been simultaneously published in the N Engl J Med journal.

On April 22, 2021, the FDA granted accelerated approval to dostarlimab for the treatment of adult patients with dMMR recurrent or advanced endometrial cancer whose disease has progressed following prior platinum-based chemotherapy.

In August of the same year, the FDA granted accelerated approval to dostarlimab for a new indication, treating patients with dMMR recurrent or advanced solid tumors. These patients experienced disease progression during or after prior treatment and have no satisfactory alternative treatment options.