A pair of phase 3 trials suggest that sugemalimab provides a progression-free survival (PFS) benefit for patients with non-small cell lung cancer (NSCLC), both as consolidation after chemoradiotherapy and in combination with chemotherapy.
In the GEMSTONE-301 trial, sugemalimab consolidation after concurrent or sequential chemoradiotherapy improved PFS for patients with unresectable, stage III NSCLC.1
In the GEMSTONE-302 trial, adding sugemalimab to platinum-based chemotherapy improved PFS for patients with metastatic NSCLC.2
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Results from both trials were published in The Lancet Oncology alongside a related editorial.3
GEMSTONE-301 Results
The GEMSTONE-301 trial (ClinicalTrials.gov Identifier: NCT03728556) included 381 patients with unresectable, stage III NSCLC at 50 sites in China who had not progressed following concurrent or sequential chemoradiotherapy.1 Patients were randomly assigned 2:1 to receive consolidation therapy with sugemalimab (n=255) or matched placebo (n=126).
The median PFS was significantly longer in the sugemalimab arm than in the placebo arm — 9 months and 5.8 months, respectively (stratified hazard ratio [sHR], 0.64; 95% CI, 0.48-0.85; P =.0026). The 12-month PFS rates were 45.4% and 25.6%, respectively.
Overall survival (OS) data were not mature at the preplanned interim analysis. However, the authors reported that 13% of patients who received sugemalimab had died, compared with 25% of patients who received placebo, suggesting a possible OS benefit with sugemalimab.
The rates of treatment-emergent and treatment-related adverse events (AEs) were higher in the sugemalimab group than the placebo group. The rate of treatment-related serious AEs was 15% with sugemalimab and 10% with placebo.
The most common AEs in both groups were pneumonitis, pneumonia, and interstitial lung disease. AEs led to study discontinuation in 11% of patients in the sugemalimab group and 5% of patients in the placebo group.
Implications and Limitations
The authors noted the importance of GEMSTONE-301 as the first randomized, phase 3 trial to investigate an immune checkpoint inhibitor in patients with unresectable, stage III NSCLC who had received concurrent or sequential chemoradiotherapy.
The PACIFIC trial had demonstrated a PFS and OS benefit with durvalumab, an anti-PD-L1 antibody similar to sugemalimab, following chemoradiotherapy, which established a new standard of care for these patients.4 However, the PACIFIC trial did not include patients who received sequential chemoradiotherapy.
As the authors of the current study wrote, sequential chemoradiotherapy is widely used for patients who cannot tolerate concurrent treatment or live in parts of the world where it is inaccessible.
In the editorial about GEMSTONE-301 and -302, the authors wrote that GEMSTONE-301 provides further evidence that radiotherapy may boost the activity of immune checkpoint inhibitors.3
However, the GEMSTONE-301 researchers were not able to evaluate the efficacy of sugemalimab in women because of low enrollment (8%). The trial also excluded patients with EGFR mutations (who were found not to benefit from durvalumab in the PACIFIC trial) and ALK and ROS1 rearrangements.
The editorialists noted that questions remain about whether treatment outcomes may vary depending on the type of anti-PD-L1 antibody, the chemotherapy regimen, and other factors. There are many ongoing trials of anti-PD-L1 and PD-1 antibodies in combination with chemotherapy or radiotherapy alone.
