medwireNews: The PD-L1 inhibitor sugemalimab has shown potential both as a consolidation treatment option for inoperable, locally advanced non-small-cell lung cancer (NSCLC) as well as in combination with chemotherapy for the first-line treatment of metastatic disease.
The results of the two trials are published in The Lancet Oncology, alongside a commentary by Rafael Rosell (Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain) and Peng Cao (Nanjing University of Chinese Medicine).
They say: “[T]he new anti-PD-L1 sugemalimab improves progression-free survival [PFS] 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,” write the commentators.
“In future clinical trials, tumour 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.”
GEMSTONE-301: Sugemalimab for stage III NSCLC
In this double-blind, phase 3 trial, 381 Chinese patients with stage III, unresectable, squamous or nonsquamous disease (lacking sensitizing EGFR, ALK, or ROS1 alterations) that had not progressed after concurrent or sequential radiotherapy were randomly assigned to receive intravenous sugemalimab 1200 mg or placebo every 3 weeks as consolidation therapy for up to 24 months.
Yi-Long Wu (Guangdong Academy of Medical Sciences, Guangzhou, China) and co-workers report on the prespecified interim analysis, conducted at a median follow-up of 14.3 months in the sugemalimab group (n=255) and 13.7 months in the placebo group (n=126).
The primary endpoint of PFS as assessed by blinded independent central review was significantly improved among sugemalimab- compared with placebo-treated patients, at a median of 9.0 versus 5.8 months, and a stratified hazard ratio (HR) for disease progression or death of 0.64. The 12-month PFS rates were 45.4% and 25.6%, respectively.
The investigators note that overall survival (OS) data were not mature at the time of data cutoff, “but initial analysis shows an HR of 0.4, favouring sugemalimab,” and follow-up is ongoing.
“The safety profile was consistent with that previously reported for sugemalimab monotherapy, with no new safety signals observed,” they continue. The specifics of the key safety data are outlined in the table.
The team concludes: “Overall, efficacy and safety data from GEMSTONE-301 support the potential use of sugemalimab as an effective consolidation therapy for patients with unresectable stage III NSCLC, whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion.”
GEMSTONE-302: Sugemalimab plus chemotherapy for stage IV NSCLC
This double-blind, phase 3 study was also conducted in China and enrolled 479 individuals with treatment-naïve, stage IV squamous or nonsquamous NSCLC without known EGFR sensitizing mutations, or ALK, ROS1, or RET fusions.
Participants were randomly assigned to receive either sugemalimab 1200 mg (n=320) or placebo (n=159) every 3 weeks alongside up to four cycles of chemotherapy (carboplatin plus pemetrexed for nonsquamous and carboplatin plus paclitaxel for squamous disease), followed by maintenance with sugemalimab or placebo for up to 35 cycles, with pemetrexed given to patients with nonsquamous disease.
The addition of sugemalimab instead of placebo to chemotherapy was associated with a significant improvement in the primary endpoint of investigator-assessed PFS at both the preplanned interim analysis (median follow-up, 8.6 months) and the final analysis (median follow-up, 17.8 months), with stratified HRs for progression or death of 0.50 and 0.48, respectively, in favor of the PD-L1 inhibitor.
The median PFS durations at the interim analysis were 7.8 months with sugemalimab and 4.9 months with placebo, with corresponding durations at the final analysis of 9.0 and 4.9 months. The estimated 12-month PFS rates were 36.4% and 14.8% in the sugemalimab and placebo groups, respectively.
“Subgroup analysis suggested these benefits were maintained regardless of PD-L1 expression and NSCLC subtype,” highlight Caicun Zhou (Tongji University School of Medicine, Shanghai, China) and team.
They add that “the data were not mature enough for the predefined formal analysis of overall survival,” but preliminary findings showed that OS favored the addition of sugemalimab to chemotherapy, with a stratified HR of 0.67 versus placebo.
Sugemalimab plus chemotherapy appeared to be “well tolerated,” and “[t]he addition of sugemalimab did not appear to increase the frequency of adverse events commonly associated with chemotherapy regimens,” say the researchers. The details of the safety data are given in the table.
Zhou and colleagues conclude that “the addition of sugemalimab to platinum-based chemotherapy showed statistically significance and clinically meaningful improvement in progression-free survival,” therefore “supporting its application as a new first-line treatment option for patients with metastatic NSCLC.”
Safety data | ||
GEMSTONE-301 | Sugemalimab | Placebo |
Grade 3 or 4 TRAEs | 9% | 6% |
Discontinuation due to TRAEs | 9% | 3% |
Treatment-related deaths | Four | None |
GEMSTONE-302 | Sugemalimab plus chemotherapy | Placebo plus chemotherapy |
Grade 3 or 4 TRAEs | 54% | 56% |
Discontinuation of any treatment due to TRAEs | 14% | 9% |
Discontinuation of sugemalimab or placebo due to TRAEs | 10% | 5% |
Treatment-related deaths | 10 | Two |
Abbreviations: TRAEs – treatment-related adverse events
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group
Lancet Oncol 2022; doi:10.1016/S1470-2045(21)00630-6
Lancet Oncol 2022; doi:10.1016/S1470-2045(21)00650-1
Lancet Oncol 2022; doi:10.1016/S1470-2045(21)00698-7