Sugemalimab Shows Survival Benefit Over Chemotherapy in Advanced NSCLC

Investigators of the GEMSTONE-302 trial announced finding a statistically significant benefit in overall survival with sugemalimab in patients with non–small cell lung cancer.

Sugemalimab, a targeted anti–PD-L1 monoclonal antibody, demonstrated a statistically significant increase in overall survival (OS) outcomes versus chemotherapy alone as a first-line treatment for patients with stage IV non–small cell lung cancer (NSCLC), according to an interim analysis of the GEMSTONE-302 trial (NCT03789604).1

OS benefit was a key secondary end point of the trial, which already reported meeting its primary end point of progression-free survival (PFS) in results recently published in The Lancet Oncology.2 These new findings from the trial were shared in a press release and will be presented in detail at an upcoming medical meeting, according to EQRx, Inc. and its partner CStone Pharmaceuticals.

“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.1

The double-blind phase 3 trial enrolled 479 patients with histologically or cytologically confirmed stage IV NSCLC who have not been previously treated. They were randomized 2:1 to either 1200 mg of sugemalimab intravenously every 3 weeks plus carboplatin-based chemotherapy versus a placebo and chemotherapy.

Patients with squamous NSCLC received paclitaxel with chemotherapy, while those with non-squamous disease received pemetrexed (Alimta). After 4 cycles, this was followed by maintenance therapy with sugemalimab or placebo for patients with squamous disease and sugemalimab or placebo plus pemetrexed for those with non-squamous disease. Patients were stratified by ECOG performance status, PD-L1 expression, and tumor pathology.

In the final analysis at the data cut-off of March 15, 2021, there was a median follow-up of 17.8 months.2 The median PFS was 9.0 months for the sugemalimab group (95% CI, 7.4-10.8) versus 4.9 months (95% CI, 4.8-5.1) for the placebo (stratified HR, 0.48; 95% CI, 0.39-0.60; P < .0001). The statistically significant PFS benefit was seen across both squamous and non-squamous subgroups and regardless of PD-L1 expression.

The safety profile displayed in the trial was consistent with other drugs in the PD-1/PD-L1 class, with both arms showing similar rates of grade 3 and 4 adverse events (AEs).2 Treatment-related serious AEs occurred in 73 patients (23%) in the sugemalimab group and 31 patients (20%) in the placebo group. Decreased neutrophil count of grade 3 or higher was reported in 33% of both arms, while decreased white blood cell count occurred in 14% in the sugemalimab arm compared with 17% in the placebo arm.

In addition to the GEMSTONE-302 trial, the companies are also investigating sugemalimab in the GEMSTONE-301 trial (NCT03728556) as a consolidation therapy in patients with locally advanced, unresectable stage III NSCLC that has not progressed following sequential or concurrent chemoradiotherapy. This trial also showed significant PFS benefit.3

“Price remains a barrier to accessing innovative therapies for many people with lung cancer around the world, despite the availability of multiple anti–PD-(L)1 therapies,” Miller said in the press release.1 “We look forward to engaging with global regulatory authorities with the aim of delivering a lower-cost treatment option to patients upon approval.”

References:

1. Sugemalimab demonstrates statistically significant overall survival benefit in patients with stage IV non­–small cell lung cancer. EQRx, Inc. Published January 18, 2022. Accessed January 24, 2022. https://bit.ly/3KKWCo6

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. Published online January 14, 2022. https://bit.ly/3tZlJxM

3. Zhou Q, Chen M, Jiang O, et al. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. Published online January 14, 2022. https://bit.ly/3r4ZN2j