Sugemalimab/Chemotherapy Combo Yields Statistically Significant Improvement in Overall Survival vs Placebo for NSCLC

Treatment with sugemalimab plus chemotherapy prolonged overall survival (OS) and yielded a statistically significantly and clinically meaningfully improved progression-free survival (PFS) compared with placebo plus chemotherapy for patients with stage IV non–small cell lung cancer, according to results from the phase 3 GEMSTONE-302 trial (NCT03728556).¹

Clinical benefit was observed in the sugemalimab arm regardless of squamous or non-squamous histology and PD-L1 expression. The full results of this analysis will be submitted for presentation at an upcoming conference.

At the prespecified interim analysis, the GEMSTONE-302 trial met its primary end point of PFS among those receiving sugemalimab compared with the placebo. Patients in the sugemalimab group had a median PFS of 7.8 months (95% CI, 6.9-9.0) compared with 4.9 months (95% CI, 4.7-5.0) in the placebo group (HR, 0.50; 95% CI, 0.39-0.64; P<.0001). The 12- and 24-month OS rates in the sugemalimab cohort were 72.4% (95% CI, 67.0%-77.0%) and 47.1% (95% CI, 37.2%-56.4%), respectively compared with 62.0% (95% CI, 53.6%-69.3%) and 38.1% (95% CI, 27.2%-49.0%), respectively, in the placebo cohort.

“We are highly encouraged to see that sugemalimab in combination with chemotherapy demonstrates significant clinical benefit, including improvement in both PFS and OS, when compared to placebo plus chemotherapy across a broad spectrum of patients with stage IV non-small cell lung cancer in this phase 3 study,” Vince Miller, MD, physician-in-chief at EQRx, said in the press release.²

A total of 479 patients were randomly assigned to either the sugemalimab group (n = 320) or the placebo group (n = 159). Patients had a median follow-up of 8.6 months for the prespecified interim PFS analysis, with the final PFS analysis having an additional 9.2 months of follow-up. Findings from the analysis indicated that 75% of patients in the sugemalimab group and 93% of in the placebo group discontinued treatment because of disease progression in 168 vs 115 patients, respectively. In the sugemalimab group, 79 patients compared with 12 in the placebo were still receiving treatment.

Patients were randomized 2:1 to either the experimental cohort or control cohort. Those in the experimental cohort received 1200 mg of intravenous sugemalimab every 3 weeks plus carboplatin at 5 mg/mL per minute and 175 mg/m2 of paclitaxel for squamous disease or carboplatin plus 500 mg/m2 of pemetrexed on day 1 of each 3-week cycle for patients with non-squamous disease. The control group received placebo plus the same chemotherapy backbone for squamous and non-squamous histology, respectively.

The median duration of study treatment was 7.2 months in the sugemalimab group and 4.6 in the placebo group, with 141 patients in the sugemalimab group and 99 in the placebo group receiving at least 1 follow-up anti-cancer therapy. A total of 44 patients in the placebo group crossed over to receive at least 1 dose of the sugemalimab monotherapy, and 20 patients received additional immunotherapy.

Findings from the prespecified PFS final analysis indicated that 223 deaths in the sugemalimab arm and 135 in the placebo arm occurred. The median PFS in the sugemalimab group was 9.0 months (95% CI, 7.4-10.8) and 4.9 months (95% CI, 4.8-5.1) in the placebo group (HR, 0.48; 95% CI, 0.39-0.60; P <.0001). The 12-month PFS rate in the sugemalimab group was 36.4% (95% CI, 31.0%-41.8%) and 14.8% (95% CI, 9.7%-21.1%) in the placebo group.

In total, 155 patients in the sugemalimab group and 113 in the placebo group progressed or died. Grade 3/4 adverse effects (AEs) occurred in 172 patients in the sugemalimab group and 89 in the placebo group, with the most common being decreased neutrophil count (33% vs 33%), decreased white blood cell count (14% vs 17%), anemia (13% vs 11%), and decreased platelet count (10% vs 9%). In total, 46 patients in the sugemalimab group and 14 in the placebo had AEs that led to discontinuation.

Forty-six patients in the sugemalimab cohort also experienced AEs that led to chemotherapy reduction vs 29 in the placebo cohort. A total of 19 patients in the sugemalimab group and 9 in the placebo group died from AEs. Fatal AEs occurred in 10 patients in the sugemalimab group and 2 in the placebo group. Immune-related treatment-emergent AEs occurred in 80 patients in the sugemalimab cohort and 5 in the placebo cohort, most of which were grade 1 and 2.

References

1. 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;S1470-2045(21)00650-1. doi:10.1016/S1470-2045(21)00650-1

2. Sugemalimab demonstrates statistically significant overall survival benefit in patients with stage IV non–small cell lung cancer. News Release. EQRx Inc. January 18, 2022. Accessed January 19, 2022. https://bit.ly/3AdK6bX