In patients with either squamous or non-squamous non-small cell lung cancer (NSCLC), adding sugemalimab—a programmed death-ligand 1 (PD-L1) inhibitor—to chemotherapy significantly and consistently improved progression-free survival (PFS) compared with placebo plus chemotherapy, regardless of patients’ PD-L1 expression, according to interim results from the GEMSTONE-302 study, published in Lancet Oncology.

For this randomized, double-blind, phase II trial, researchers led by Caicun Zhou, MD, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China, sought to assess both the efficacy and safety of sugemalimab plus chemotherapy in patients with metastatic NSCLC.

They enrolled 479 patients (median age: 62-64 years; 79%-81% male; 73%-75% current or former smokers) from 35 hospitals and research centers throughout China with stage IV squamous (roughly 40%) or non-squamous (roughly 60%) NSCLC, who had no known EGFR sensitizing mutations, ALK, ROS1, or RET fusions; no previous systemic treatment; and an ECOG performance status of 0 or 1. In all, approximately 40% of patients in both treatment groups had a PD-L1 expression of less than 1%, and about 60% exhibited expression of 1% or greater.

Patients were randomized to sugemalimab (1,200 mg IV every 3 weeks) plus platinum-based chemotherapy comprised of carboplatin and paclitaxel for those with squamous NSCLC; or carboplatin and pemetrexed for non-squamous NSCLC; or placebo plus identical platinum-based chemotherapy regimens for both squamous and non-squamous NSCLC for up to four cycles. These regimens were then followed by maintenance therapy with sugemalimab or placebo for patients with squamous NSCLC, and IV sugemalimab or matching placebo plus pemetrexed for non-squamous NSCLC.

The primary endpoint of the study was PFS as assessed by investigators in the intention-to-treat population. Researchers also analyzed safety in patients who received at least one treatment dose.

At a median follow up of 8.6 months, during a preplanned interim analysis, researchers reported that the primary endpoint of the study was met—patients treated with sugemalimab had significantly longer PFS compared to those in the placebo group (median: 7.8 vs 4.9 months, respectively; stratified HR: 0.50; 95% CI: 0.39-0.64; P<0.0001). These improvements were maintained for the final analysis, conducted at a median follow-up of 17.8 months (median: 9.0 vs 4.9 months; stratified HR: 0.48; 95% CI: 0.39-0.60; P<0.0001).

Estimated 12-month PFS was 36.4% in the sugemalimab group compared with 14.8% in placebo. Although the data for median overall survival was immature, it was also significantly longer in patients treated with the addition of sugemalimab (22.8 vs 17.7 months, respectively; HR: 0.67; 95% CI: 0.50-0.90; log-rank P=0.0064).

As far as the safety of sugemalimab, Zhou et al concluded that the drug was well tolerated.

“The addition of sugemalimab did not appear to increase the frequency of adverse events commonly associated with chemotherapy regimens,” they wrote. “The incidence of most immune-mediated treatment-emergent adverse events was not higher with sugemalimab plus chemotherapy than with sugemalimab monotherapy. No unexpected safety signals were found. Of special interest, immune-related treatment-emergent adverse event profiles in the sugemalimab group were mostly grade 1–2 and generally consistent with the known profiles of products in the same class.”

In all, 23% of patients treated with sugemalimab had any treatment-related serious adverse events, compared with 20% of those in the placebo group. The most common grade 3/4 treatment-related adverse events included the following:

  • Decreased neutrophil count in 33% of sugemalimab patients versus 33% placebo.
  • Decreased white blood cell counts in 14% versus 17%, respectively.
  • Anemia in 13% versus 11%.
  • Decreased platelet count in 10% versus 9%.
  • Neutropenia in 4% in each treatment group.

Treatment-related deaths occurred in 3% of patients treated with sugemalimab and were caused by pneumonia with respiratory failure (n=1); myelosuppression with septic shock (n=1); pneumonia (n=2); respiratory failure, abdominal pain, cardiac failure, and immune-mediated pneumonitis (n=1 each); and unspecified causes (n=2).

In their accompanying comment, Rafael Rosell, MD, of the Laboratory of Molecular Biology, Institut d´Invesigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain, and Peng Cao, PhD, of Nanjing University of Chinese Medicine, China, and the Zhenjiang Hospital of Chinese Traditional and Western Medicine, China, noted that these results from GEMSTONE-302 were similar to those from the KEYNOTE-189 study, in which pembrolizumab added to pemetrexed-platinum chemotherapy brought about similar improvements in PFS and median overall survival.

Pembrolizumab is a humanized monoclonal immunoglobulin (Ig) G2 antibody directed against PD-1 that prevents binding and activation of PD-L1 and PD-L2.

“Notably, progression-free survival improved in the GEMSTONE-302 study regardless of histology. As in KEYNOTE-189, benefit was also seen irrespective of the extent of tumor PD-L1 expression,” they added.

These interim results from GEMSTONE-302 add to numerous studies of anti-PD-L1 agents.

“A total of 23 trials of PD-1 and PD-L1 antibodies are in progress, including sugemalimab, in NSCLC. There are 33 immunotherapy trials with chemoradiotherapy and 44 with radiotherapy alone,” noted Rosell and Cao.

“In summary, the new anti-PD-L1 sugemalimab improves progression-free survival in either unresectable or metastatic NSCLC (GEMSTONE-301 and GEMSTONE-302) and adds further evidence to the benefit of immunotherapy in this setting. Nevertheless, the presence of some co-mutations can predict an inadequacy of immunotherapy effectiveness. In future clinical trials, tumor tissue or circulating plasma DNA analysis by next-generation sequencing should be considered to help gauge checkpoint immunotherapy response and to look for therapies that can avert immune evasion,” they concluded.

Limitations of the study include immature overall survival data and need for longer follow-up.


This study was funded by CStone Pharmaceuticals.

Zhou reports speaker honoraria from CStone Pharmaceuticals during the course of this study and, outside of this study, reports speaker honoraria from Lilly China, Sanofi, Boehringer Ingelheim, Roche, MSD, Qilu Pharmaceutical, Hengrui Therapeutics, Innovent Biologics, Luye Pharma Group, TopAlliance Biosciences, and Amoy Diagnostics; and is an advisor for Innovent Biologics, Hengrui Therapeutics, Qilu Pharmaceutical, and TopAlliance Biosciences.

Some study co-authors were employed or funded by CStone Pharmaceuticals.

Rosell and Cao reported no disclosures.



Liz Meszaros, Deputy Managing Editor, BreakingMED™

Kaiser Health News

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