Dostarlimab, a monoclonal antibody targeting PD-1, showed strong and durable antitumor activity in patients with mismatch repair–deficient (dMMR) gastrointestinal tumors in the phase I GARNET study, reported Thierry André, MD, of Sorbonne Université and Hôpital Saint Antoine, Paris, and colleagues at the 2021 Gastrointestinal Cancers Symposium (Abstract 9).
“The majority of patients were enrolled with advanced disease that had progressed on prior therapy and they had limited treatment options. This represents a patient group with a high unmet need,” said Dr. André. “Dostarlimab demonstrated durable antitumor activity in a cohort [of patients] with dMMR colorectal and non–colorectal cancer tumors, and it has a convenient schedule of administration. It’s clear that dostarlimab works well in refractory disease…it’s good news for [patients with] gastrointestinal cancer[s].”
Thierry André, MD
GARNET Study
The ongoing phase I GARNET study is evaluating dostarlimab in patients with a variety of advanced solid tumors whose disease progressed following systemic therapy. Dr. André presented findings from cohort F, which included patients with locally determined dMMR/microsatellite instability–high (MSI-H) or POLE-mutated nonendometrial solid tumors, the majority of which were gastrointestinal. Other cohorts include patients with endometrial cancer, non–small cell lung cancer, and prostate cancer. Patients received dostarlimab at 500 mg every 3 weeks for four cycles, and 1,000 mg of dostarlimab every 6 weeks thereafter for up to 2 years.
Dr. André reported safety findings for 144 patients and efficacy findings for 106 dMMR patients, of whom 99 (93.4%) had gastrointestinal tumors, including 69 (65%) with colorectal cancer, 12 (11%) with small intestine cancer, and 8 (8%) with gastric or gastroesophageal junction cancer. The majority of patients had received two or three prior lines of treatment.
The confirmed objective response rate was 38.7%, with a complete response rate of 7.5%. Responses were consistent across both colorectal and noncolorectal tumor types, Dr. André reported.
For the 41 responding patients, median duration of response had not been reached after a median of 12.4 months of follow-up. The probability of maintaining a response at 12 and 18 months was 91.0% and 80.9%, respectively. Responses were durable across tumor types, he added.
KEY POINTS
- The confirmed objective response rate was 38.7%, with a complete response rate of 7.5%.
- Treatment-related adverse events were reported in 69% of patients, of which 8% were grade ≥ 3; treatment-related serious adverse events were observed in 6% of patients, and toxicities leading to discontinuation of treatment occurred in 4%.
Treatment-related adverse events were reported in 69% of patients, of which 8% were grade ≥ 3; treatment-related serious adverse events were observed in 6% of patients, and toxicities leading to discontinuation of treatment occurred in 4%. No deaths associated with dostarlimab were reported.
The safety profile was consistent with other cohorts in GARNET, with immune-related adverse events infrequent and being of low grades.
The cohort is open for further enrollment. Data for the whole cohort with dMMR/MSI-H disease determined centrally will be reported in the future, said Dr. André.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
