Sugemalimab Receives Approval in China for Relapsed/Refractory Extranodal NK/T-cell Lymphoma

The National Medical Products Administration (NMPA) of China has approved sugemalimab (Cejemly) for use in patients with relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (ENKTL).¹

The decision is based on the phase 3 GEMSTONE-201 study (NCT05700448) in which the PD-L1 antibody elicited an objective response rate (ORR) of 44.9% (95% CI, 33.6%-56.6%) by independent radiology review committee (IRRC) assessment in evaluable patients (n = 78), which included a complete response (CR) rate of 35.9%.² The median DOR was not yet reached (NR; 95% CI, 19.7-not reached). The 6-month DOR rate was 91.3% (95% CI, 75.5%-97.1%), the 12-month DOR rate was 82.5% (95% CI, 62.0%-92.6%), and the 18-month DOR rate was 82.5% (95% CI, 62.0%-92.6%).

“We very much appreciate the attention from the NMPA of China to the rare disease like NK/T-cell lymphoma. Patients with R/R ENKTL have had no standard of care and very limited treatment options over the years, leading to very short survival durations, and therefore, significantly unmet medical needs,” Professor Huang Huiquang, MD, PhD, of Sun Yat-sen University Cancer Center, and lead principal investigator of the study, stated in a press release.¹ “In the GEMSTONE-201 study, sugemalimab monotherapy has demonstrated notable antitumor activity, durable objective response, and manageable safety in patients with R/R ENKTL. Following this approval, we look forward to seeing more patients with R/R ENKTL having access to sugemalimab in the near future.”

The single-arm GEMSTONE-201 trial enrolled patients with histologically confirmed nasal and non-nasal ENKTL that was refractory to or relapsed following asparagine-based chemotherapy or chemoradiation.2 They needed to be between the ages of 18 and 75 years, have 1 or more measurable or evaluable lesions by 2014 Lugano classification, an ECOG performance status of 0 to 1, acceptable organ function, and a life expectancy of at least 12 weeks.

If they had aggressive NK-cell leukemia or hemophagocytic lymphohistiocytosis, primary or secondary central nervous system involvement, or prior exposure to a PD-1/PD-L1 or anti-cytotoxic T-cell lymphocyte-4 treatment, they were excluded. Other exclusion criteria included having received previous chemotherapy, immunotherapy, biological therapy; having undergone a major surgical procedure within 28 days; or having received radiotherapy within 90 days prior to the first dose of the study drug; among others.

Study participants were given 1200 mg of sugemalimab intravenously every 3 weeks as part of a 21-day treatment cycle. Treatment was continued for up to 2 years or until disease progression, unacceptable toxicity, withdrawn consent, or death.

The trial’s primary end point was IRRC-assessed ORR, and key secondary end points comprised ORR by investigator assessment, IRRC- and investigator-assessed CR rate, duration of response (DOR), and safety.

In the 80 total patients, the median age was 48.0 years (range, 29.0-74.0), and 63.8% were male. Most patients had an ECOG performance status of 1 (73.8%) and stage IV disease at the time of screening (67.5%). Regarding prior lines of treatment, 51.3% had 1 line, 27.5% had 2 prior lines, and 21.3% had 3 or more. Additionally, 53.8% of patients had relapsed disease and 46.3% had refractory disease. Moreover, 6.3% had bone marrow involvement and 7.5% underwent prior autologous hematopoietic stem cell transplant. More than half of patients (61.3%) previously received radiotherapy.

The data cutoff date was February 23, 2022, for the primary analysis of the trial. Sugemalimab elicited an investigator-assessed ORR of 45.6% (95% CI, 34.3%-57.2%), with a CR rate of 30.4%. The median DOR was NR (95% CI, 13.9-NR). The DOR rates at 6, 12, and 18 months were 76.9% (95% CI, 59.0%-87.8%), 72.7% (95% CI, 53.5%-84.9%), and 67.5% (95% CI, 46.8%-81.6%). The concordance rate between ORRs by IRRC and investigator assessment was 95.7%.

Moreover, the median overall survival (OS) was NR (95% CI, 14.0-NR). The 6-month OS rate was 79.2% (95% CI, 68.3%-86.7%), the 12-month OS rate was 67.5% (95% CI, 55.4%-77.0%), and the 18-month OS rate was 57.9% (95% CI, 44.9%-68.9%).

Regarding safety, 96.3% of patients experienced at least 1 treatment-emergent adverse effect (TEAE); these effects were grade 3 or higher for 40.0% of patients. Treatment-related AEs were reported in 78.8% of patients and these effects were grade 3 or higher for 16.3% of patients. Serious AEs occurred in 23.8% of patients.

The most common any-grade TRAEs experienced by at least 10% of patients included decreased white blood cell count (22.5%), hypothyroidism (18.8%), decreased neutrophil count (16.3%), increased aspartate aminotransferase (15.0%), pyrexia (15.0%), rash (12.5%), increased alanine aminotransferase (11.3%), and increased blood thyroid-stimulating hormone (11.3%).

TEAEs resulted in discontinuation for 13.8% of patients, with 6.3% of effects related to treatment. Two patients experienced increased blood bilirubin, 1 patient had cellulitis orbital, 1 patient had pyrexia, and 1 patient had facial nerve disorder. Five patients died because of AEs, although the deaths were not attributed to sugemalimab.

References

1. CStone announces NMPA approval of sugemalimab for patients with relapsed or refractory extranodal NK/T-cell lymphoma, the first anti-PD-1/PD-L1 mAB approved for this indication. News release. CStone Pharmaceuticals. October 31, 2023. Accessed November 21, 2023. https://www.cstonepharma.com/en/html/news/3635.html
2. 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. 2022;41(suppl 16):3032-3041. doi:10.1200/JCO.22.02367