Sugemalimab Represents a Promising Treatment Option for R/R ENKTL

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Sugemalimab showed robust and durable antitumor activity in relapsed or refractory (R/R) extranodal natural killer/T-cell lymphoma (ENKTL), and treatment with the agent was well-tolerated with an expected safety profile, according to published results from the phase 2 GEMSTONE-201 trial (NCT03595657).¹

At the data cutoff, the independent radiologic review committee-assessed overall response rate (ORR) was 44.9% (95% CI, 33.6-56.6). Twenty-eight (35.9%) patients reached a complete response and 7 (9.0%) achieved a partial response, with a response rate of 82.5% at 12-months (95% CI, 62.0-92.6).

“[S]ugemalimab showed potent, durable antitumor activity and a manageable safety profile in the largest study of an immune checkpoint inhibitor in patients with R/R ENKTL, representing a promising treatment option for patients with this rare and aggressive disease,” wrote study authors in findings published in the Journal of Clinical Oncology.

This single-arm phase 2 study evaluated the efficacy and safety of sugemalimab, an anti–PD-L1 monoclonal antibody, in R/R ENKTL at 16 centers across China. Patients were given sugemalimab 1,200 mg intravenously once every 3 weeks for up to 24 months or until progression, death, or study withdrawal.

Patients enrolled in the trial were aged 18-75 years who had histologically confirmed nasal and non-nasal ENKTL that was refractory to or relapsed after asparaginase-based chemotherapy or chemoradiotherapy. Other requirements were to have at least 1 measurable or evaluable lesion as per 2014 Lugano classification, provide immunohistochemically stained tumor tissue sections and corresponding pathologic reports or unstained tumor tissue sections for central pathology review, an ECOG performance status score of 0 or 1, adequate organ function, and a life expectancy of ≥12 weeks.^1,2

The primary end point assessed in the trial was ORR assessed by an independent radiologic review committee and the secondary end points consisted of ORR assessed by the investigators, complete response rate, duration of response (DOR), and safety.

A total of 80 patients were enrolled by the data cutoff date of February 23, 2022, and followed for a median of 18.7 months. The median age among patients was 48.0 (range, 29.0-74.0) years, and 59 (73.8%) patients had an ECOG performance status score of 1. Fifty-four (67.5%) patients had stage IV disease and 39 (48.8%) had received ≥2 lines of prior systemic therapy. Additionally, 58 (72.5%) patients had discontinued treatment because of disease progression (41.3%), adverse events (AEs; 13.8%), withdrawal by patient (10.0%), symptomatic deterioration without radiographic evidence of progression (6.3%), and death (1.3%), and 22 (27.5%) patients were still receiving treatment.

The investigator-assessed ORR was 45.6% (95% CI, 34.3 to 57.2), and a total of 24 (30.4%) patients achieved a complete response. The median DOR was not reached (95% CI, 19.7 months-not reached) while the 6-, 12-, and 18-month DOR rates were 91.3% (95% CI, 75.5-97.1), 82.5% (95% CI, 62.0-92.6), and 82.5% (95% CI, 62.0-92.6), respectively.¹

Further, the median overall survival (OS) was also not reached (95% CI, 14.0-not reached) which at 6-, 12-, and 18-months, the OS rates were 79.2% (95% CI, 68.3-86.7), 67.5% (95% CI, 55.4-77.0), and 57.9% (95% CI, 44.9-68.9), respectively.

For safety, most treatment-emergent AEs were grade 1-2, and grade ≥ 3 events were reported in 32 (40.0%) patients. Most treatment-related AEs were also grade 1 or 2 in severity while grade 3 or 4 events were reported in 13 (16.3%) patients. These included increased aspartate aminotransferase and anemia occurring in 2 (2.5%) patients each, and the other events occurred in 1 (1.3%) patient each. Serious AEs were observed in 19 (23.8%) patients. A total of 6 serious AEs (7.5%) were considered related to treatment and all except 1 event of sinus node dysfunction resolved at the data cutoff date without sequelae. Additionally, AEs of special interest occurred in 25 (31.3%; patients with 2 (2.5%) patients reporting grade ≥ 3 AEs.

The study drug was discontinued because of treatment-emergent AEs seen in 11 (13.8%) patients, including increased blood bilirubin in 2 (2.5%) patients, and cellulitis orbital, pyrexia, and facial nerve disorder in 1 (1.3%) patient each. All AEs were grade 1 or 2 events. Moreover, 5 (6.3%) patients died due to AEs. However, they were not attributed to sugemalimab, as assessed by the investigator.

Next, the agent will be studied with chemotherapy vs chemotherapy alone in a randomized, phase 3 study (NCT05700448) in patients with R/R ENKTL. This trial will further assess the efficacy and safety of sugemalimab.

REFERENCES:

1. Huang H, Tao R, Hao S, et al. Sugemalimab monotherapy for patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (GEMSTONE-201): Results from a single-arm, multicenter, phase II study. J Clin Oncol. Published March 30, 2023. doi:10.1200/JCO.22.02367

2. A study of CS1001 in subjects with relapsed or refractory extranodal natural killer/ T cell lymphoma (ENKTL). ClinicalTrials.gov. Updated November 1, 2022. Accessed April 4, 2023.