At the 2022 ASCO Annual Meeting, results from the GEMSTONE-302 trial showed that adding sugemalimab to chemotherapy improved survival in patients with metastatic non–small cell lung cancer.
The combination of sugemalimab plus chemotherapy showed statistically significant survival improvement for patients with metastatic non–small cell lung cancer (NSCLC) regardless of their tumor pathology or PD-L1 expression level when compared with placebo plus chemotherapy, according to an interim overall survival (OS) analysis of the GEMSTONE-302 study (NCT03789604) presented at the 2022 ASCO Annual Meeting.1
Results from the randomized, double-blind, phase 3 trial were first published in The Lancet showing that the trial met its primary end point of investigator-assessed progression-free survival (PFS) with significantly longer PFS in the sugemalimab arm compared with placebo at a median of 7.8 months (95% CI, 6.9-9.0) vs 4.9 months (95% CI, 4.7-5), respectively (HR, 0.50; 95% CI, 0.39-0.64; P < .0001).2
The final analysis, presented at ASCO by Caicun Zhou, PhD, MD, showed that at a median follow-up of 17.8 months (interquartile range [IQR], 15.1-20.9), PFS improvement was maintained at a median of 9 months (95% CI, 7.4-10.9) vs 4.9 months (95% CI, 4.8-5.2), respectively (HR, 0.49; 95% CI, 0.40-0.61; P < .0001). Moreover, the 2-year PFS rate was also higher in the sugemalimab plus chemotherapy group at 20.8% compared with 7.3% in the placebo group.
Median OS was reported in the interim analysis at 25.4 months (95% CI, 20.1-NR) in the sugemalimab plus chemotherapy arm compared with 16.9 months (95% CI, 12.8-20.7) in the placebo group (HR, 0.65; 95% CI, 0.50-0.84; P = .0008). This benefit with sugemalimab also extended to the 2-year OS rate at 51.7% in the treatment arm vs 35.6% in the placebo arm.
All subgroups observed in the study had OS benefits irrespective of their tumor pathology. For example, 129 patients with squamous cell NSCLC on sugemalimab plus chemotherapy had a median OS of 23.3 months compared with 12.2 months for the 63 patients on placebo plus chemotherapy (HR, 0.56; 95% CI, 0.38-0.82). Similar results were then observed in the nonsquamous subgroup on the trial with a median OS of 26.9 months for 191 patients on the treatment arm vs 19.8 months for the 96 patients on the placebo arm (HR, 0.72; 95% CI, 0.51-1.01).
Patients also had improved OS regardless of their PD-L1 tumor proportion scores, Zhou, director of the Department of Oncology, Shanghai Pulmonary Hospital, noted. Those patients with expression levels 1% or greater had a median OS of 27 months vs 19 months (HR, 0.64; 95% CI, 0.46-0.91) in the placebo group and patients with less than 1% of expression had a median OS of 19.4 months vs 14.8 months, respectively (HR, 0.66; 95% CI, 0.45-0.97). PFS in both groups was improved as well at a median of 10.9 months in the sugemalimab group vs 4.9 months in the placebo group of patients with a PD-L1 expression level of 1% or more (HR, 0.48; 95% CI, 0.36-0.63; P < .0001), and 7.4 vs 4.9 months for patients with less than 1% expression, respectively (HR, 0.57; 95% CI, 0.41-0.78; nominal P = .0005).
The overall response rate (ORR) and duration of response (DOR) were also longer in the sugemalimab arms, researchers found. In the intent-to-treat population, ORR was 63.4% in the sugemalimab arm vs 40.3% in the placebo arm (P < .0001) and median DOR was 9.9 months (range, 0.7-31.5) in the sugemalimab arm vs a median of 4.4 months (range, 0+ to 26.0+) in the placebo arm.
As with the other data in the interim analysis, irrespective of tumor histology or PD-L1 expression, the patients on sugemalimab plus chemotherapy arm experienced better response rates and longer DOR. In the nonsquamous group there was a 58.6% ORR compared with a 70.5% ORR in patients with squamous cell NSCLC for the sugemalimab-treated patients compared with 36.5% and 46%, respectively, on placebo. Patients with a PD-L1 expression of 1% or greater had the highest ORR at 70.9% vs 51.6% on sugemalimab and 41.1% and 39.1% for those with less than 1% in the placebo group, respectively.
The trial was conducted across 35 hospitals and academic research centers in China ultimately enrolling 479 patients randomly assigned 2:1 to receive either 1200 mg of sugemalimab (n = 320) intravenously every 3 weeks plus platinum-based chemotherapy of area under the curve (AUC) 5 mg/mL per min of carboplatin and 175 mg/m2 of paclitaxel if they had squamous NSCLC. For patients with nonsquamous NSCLC, they were given the same amount of carboplatin and 500 mg/m2 of pemetrexed, intravenously. The groups of patients on placebo (n = 159) were given the same platinum-based chemotherapy regimens for squamous or nonsquamous NSCLC as in the sugemalimab group up to 4 cycles. This was then followed by maintenance therapy with 500 mg/m2 sugemalimab, or placebo, for patients with squamous NSCLC, whereas patients with nonsquamous NSCLC were given either sugemalimab or matching placebo plus pemetrexed.
As of November 22, 2021, 51 patients (15.9%) remained on treatment with sugemalimab plus chemotherapy and 7 patients (4.4%) remained on placebo plus chemotherapy. Many patients went on to receive 1 or more subsequent anti-cancer therapies, with 65.4% in the placebo group going on to do so compared with 49.1% in the sugemalimab plus chemotherapy group. Moreover, 45 patients in the placebo plus chemotherapy arm received on-study crossover sugemalimab after disease progression and 43.4% of patients in the placebo arm received anti–PD-L1 treatment compared with 17.8% of those eligible in the sugemalimab group.
Treatment-emergent adverse events (TEAEs) were comparable in both groups, explained Zhou, and there no new safety signals identified since the last report on this study, he added. All patients had at least one TEAE in either group, with the most common grade 3 or 4 TEAE being a decrease of neutrophil count in 33% of patients on sugemalimab vs 33% of those on placebo, a decrease in white blood cell count (14% vs 17%, respectively), anemia (13% vs 11%), a decrease in platelet count (10% vs 9%), and neutropenia (4% vs 4%). Seventy-three patients in the sugemalimab arm had any serious TEAE compared with 31 in the placebo group, while 54.4% of patients in the sugemalimab group discontinued from the study vs 71.1% in the placebo group, with most discontinuing due to death.
“In conclusion, sugemalimab plus chemo demonstrated significant and clinically meaningful PFS, OS, and overall response rate improvement compared with placebo plus chemo…. These data support sugemalimab plus chemotherapy as first-line treatment for patients with metastatic NSCLC,” Zhou concluded.
1. Zhou C, Wang Z, Sun M, et al. A protocol pre-specified interim overall survival (OS) analysis of GEMSTONE-302: A phase 3 study of sugemalimab (suge) versus placebo plus platinum-based chemotherapy (chemo) as first-line (1L) treatment for patients (pts) with metastatic non–small cell lung cancer (NSCLC). J Clin Oncol. 2022;40(suppl 16):9027. doi:10.1200/JCO.2022.40.16_suppl.9027
2. Zhou C, Wang Z, Sun Y, et al. Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial. Lancet Oncol. 2022;23(2):220-233. doi:10.1016/S1470-2045(21)00650-1