The novel immunotherapy is a fully human anti-PD-L1 immunoglobulin G4 monoclonal antibody developed using the OmniRat transgenic animal platform (under licence from Ligand Corporation). As it is a fully human, full length antibody, it is hoped that the risk of immunogenicity and toxicity will be reduced.
In a double-blind, randomised Phase III trial, it was evaluated against a placebo in combination with platinum-based chemotherapy as a potential treatment for non-small cell lung cancer.1
In total, 479 patients were recruited who had stage 4 squamous or non-squamous NSCLC with no known EGFR sensitising mutations, ALK, ROS1 or RET fusions, and who had received no previous systemic treatment for metastatic disease.
They were given either 1200 mg of intravenous sugemalimab or a placebo every 3 weeks plus platinum-based chemotherapy — carboplatin and paclitaxel for squamous disease or carboplatin plus pemetrexed for non-squamous. Subjects were given up to four cycles of treatment, followed by antibody or placebo maintenance therapy plus pemetrexed for non-squamous disease.
During interim analysis, there was significantly longer progression-free survival in the sugemalimab group (7.8 months) compared with the placebo (4.9 months). This improvement in progression-free survival was maintained at final analysis — 9 months later — at 9.0 months compared with 4.9 months.
The most common grade 3 or 4 treatment-related adverse events were a decrease in neutrophil count, the incidence of which was similar across both groups, plus decreases in white blood cell and platelet counts, and neutropenia.
Many patients with unresectable stage 3 NSCLC cannot tolerate or access concurrent chemoradiotherapy, so sequential treatment is common and, therefore, its efficacy in patients whose disease had not progressed after either schedule was assessed in another Phase III trial.2
In all, 381 such patients were given intravenous 1200 mg doses of sugemalimab or a placebo every 3 weeks for up to 24 months. At the data cut-off point, progression-free survival was 9 months with the antibody and 5.8 months with the placebo.
Further Phase III trials are now recruiting to treat gastric and oesophageal cancers, one evaluating its efficacy and safety as a first line treatment in combination with capecitabine and oxaliplatin, and the second in combination with 5-fluorouracil and cisplatin. Both of these were promising in Phase Ib studies.3 The antibody is also being evaluated in clinical trials for other forms of cancer, including lymphoma.
References
- C. Zhou, et al., Lancet Oncol. 14 (2022): online ahead of print (doi: 10.1016/S1470-2045[21]00650-1).
- Q. Zhou, et al., Lancet Oncol. 14 (2022): online ahead of print (doi: 10.1016/S1470-2045[21]00630-6).
- L. Shen, et al., European Society for Medical Oncology (ESMO), Abstr. 1445P (2020).