Treatment with sugemalimab shown to be well-tolerated and have a consistent safety profile to other studies, according to results of the GEMSTONE-201 trial.
Findings from the single-arm, phase 2 GEMSTONE-201 trial (NCT03595657) showed sugemalimab, an anti–PD-L1 IgG4 antibody, to elicit response in nearly half of patients as well as a complete response (CR) in a third of patients with relapsed or refractory extranodal natural killer/T cell lymphoma (R/R ENKTL), according to data presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1
In the multicenter study, which enrolled 80 patients, the objective response rate (ORR) by independent regulatory review commission (IRRC) was 46.2% with sugemalimab (95% CI, 34.8%-57.8%). The complete response (CR) by IRRC was 37.2% with a median duration of response that was not yet reached (range, 1.0-33.8+). Additionally, 10.3% of patients had stable disease. At 12 months, 86% of patients continued to response to treatment with sugemalimab and the 24-month overall survival (OS) rate was 54.6%.
“GEMSTONE-201 is the largest registrational study reported to date to evaluate an anti-PD-1/ or PD-L1 antibody in patients with relapsed/refractory extranodal NKTL,” Huiqiang Huang, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, China, said during a presentation of the results. “Sugemalimab monotherapy was well-tolerated. Safety in ENKTL was consistent with the known safety profile of sugemalimab in other studies. Sugemalimab could potentially provide a new and effective treatment option for relapsed/refractory extranodal NKTL.”
In the study, 80 patients with relapsed or refractory ENKTL received sugemalimab intravenously at 1200 mg every 3 weeks for up to 24 months. The median age of patients was 48 years (range, 29-74) and approximately two-thirds were male (63.8%). The baseline ECOG performance status was 1 in most patients (73.8%), with a minority having a score of 0 (26.3%). Most patients had stage IV disease (67.5%), with the remainder having either stage I (11.3%) or stage II (21.3%). Most patients had received 1 prior line of therapy (51.3%), with 27.5% receiving 2 lines and 21.3% having received ≥3 lines at baseline. Prior autologous stem cell transplant was received by 7.5% of patients and 61.3% had received prior radiotherapy.
By investigator assessment, the ORR was 45.6% (95% CI, 34.3%-57.2%), which was a 97.1% concordance between the investigators and the IRRC. The CR rate was 30.4% by investigator assessment and at 12 months 72.3% of patients continued to respond. In this assessment, 5.1% of patients had stable disease. The median OS was not yet reached (range, 0.9-37.2+). The 12-month OS rate was 68.6% and the 6-month rate was 79.2%.
At the data cutoff of November 10, 2021, the median follow-up was 13.4 months and 23 patients remained on treatment. Of those who discontinued (n = 57), the most common cause was progressive disease (n = 33) followed by adverse events (n = 10). Treatment-emergent adverse events (TEAEs) were experienced by 96.3% of patients, with 38.8% having a grade ≥3 TEAE. Treatment-related adverse events (TRAEs) were experienced by 76.3% of patients, with 16.3% having a grade ≥3 event.
The most common TEAEs were pyrexia (30%), white blood count decreased (30%), aspartate aminotransferase increase (23.8%), neutrophil count decrease (23.8%), and hypothyroidism (21.3%). There were 5 treatment-related serious adverse events reported, namely pyrexia (n = 2), sinus node dysfunction (n = 1), pneumonia (n = 1), and myositis (n = 1). The most commonly reported immune-related adverse events (irAEs) were hypothyroidism (16.3%), hyperthyroidism (7.5%), and skin adverse reactions (6.3%). Of these, 2 were deemed grade 3 in severity (rash and hypothyroidism). There were no grade 4/5 irAEs.
“Safety in this study was consistent with the known safety profile of sugemalimab in other studies,” said Huang. “Most TRAEs were grade 1/2 events. We didn't observe any Grade 4/5 irAEs.”
Sugemalimab has received a breakthrough therapy designation for T-cell lymphoma and R/R ENKTL from the FDA, in addition to an orphan drug designation. The GEMSTONE-201 was study was conducted primarily in China, and CStone, the developer of sugemalimab, plans to submit findings from the GEMSTONE-201 study for regulatory approval in China. The company, and its partner EQRx, are currently in discussions with the FDA in the United States.