Sugemalimab is Well-Tolerated in Patients With Natural Killer/T-cell Lymphoma

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. 

Reference:

Huang H, Tao R, Yang Y, et al. GEMSTONE-201: Preplanned primary analysis of a multicenter, single-arm, phase 2 study of sugemalimab (suge) in patients (pts) with relapsed or refractory extranodal natural killer/T cell lymphoma (R/R ENKTL). J Clin Oncol. 2022;40 (suppl 16; abstr 7501). Doi: 10.1200/JCO.2022.40.16_suppl.7501