Sugemalimab Shows Promise for Natural Killer/T-cell Lymphoma

Treatment with the anti­–PD-L1 IgG4 antibody sugemalimab resulted in a response for nearly half of patients and a complete response (CR) in one-third of patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL), according to findings from the single-arm phase 2 GEMSTONE-201 study (NCT03595657) presented at the 2022 ASCO Annual Meeting.¹

Sugemalimab elicited an objective response rate (ORR) of 46.2% (95% CI, 34.8%-57.8%) by independent regulatory review commission (IRRC) among 78 evaluable patients. The 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 respond to treatment with sugemalimab. 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 on the data. “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%) disease. Most patients had received 1 prior line of therapy (51.3%), with 27.5% having received 2 lines and 21.3% having received 3 or more 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%); this 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 to treatment. 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 effects (AEs; n = 10). Treatment-emergent AEs (TEAEs) were experienced by 96.3% of patients, with 38.8% having a grade 3 or higher TEAE. Treatment-related AEs (TRAEs) were experienced by 76.3% of patients, with 16.3% having a grade 3 or higher toxicity.

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%). Five treatment-related serious AEs reported, namely pyrexia (n = 2), sinus node dysfunction (n = 1), pneumonia (n = 1), and myositis (n = 1).

The most commonly reported immune-related adverse effects (irAEs) were hypothyroidism (16.3%), hyperthyroidism (7.5%), and skin adverse reactions (6.3%). Of these, 2 were deemed to be grade 3 in severity: rash and hypothyroidism. No grade 4/5 irAEs were observed.

“Safety in this study was consistent with the known safety profile of sugemalimab in other studies,” Huang noted. “Most TRAEs were grade 1/2. We did not observe any grade 4/5 irAEs.”

Sugemalimab has received a breakthrough therapy designation for patients with T-cell lymphoma and R/R ENKTL from the FDA, in addition to an orphan drug designation.

The GEMSTONE-201 study was conducted primarily in China, and CStone, the developer of sugemalimab, plans to submit findings from the study for regulatory approval in China. The company, and its partner EQRx, are currently in discussions with the FDA in the United States.

Reference

1. 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):7501. doi: 10.1200/JCO.2022.40.16_suppl.7501