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The anti–PD-L1 monoclonal antibody CS1001 in combination with platinum-based chemotherapy led to a significant improvement in progression-free survival when used as a frontline treatment for patients with stage IV squamous and nonsquamous non–small cell lung cancer.
The anti–PD-L1 monoclonal antibody CS1001 in combination with platinum-based chemotherapy led to a significant improvement in progression-free survival (PFS) when used as a frontline treatment for patients with stage IV squamous and nonsquamous non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 CS1001-302 trial (NCT03789604).1
Results showed that the median PFS per investigator assessment was 7.8 months with the CS1001/chemotherapy combination versus 4.9 months with placebo plus chemotherapy in the overall patient population with both squamous and nonsquamous NSCLC (HR, 0.50; 95% CI, 0.39-0.64; P <.0001). Notably, the clinical benefit of the CS1001 combination was observed across histology subtypes and PD-L1 expression levels.
Moreover, the blinded independent central review–assessed PFS with CS1001 plus chemotherapy as a secondary end point proved to be consistent with the investigator-assessed PFS. Other secondary end points of the trial were also found to support the result of the primary end point.
The safety profile of CS1001 in combination with chemotherapy was found to be favorable, with no new safety signal identified.
Based on these data, CStone Pharmaceuticals, the drug developer, announced that they plan to submit a new drug application for CS1001 for use in this patient population in this setting.
“Currently, there is no anti–PD-L1 monoclonal antibody approved for NSCLC in China. CS1001 is the first anti–PD-L1 monoclonal antibody combined with chemotherapy to demonstrate significant improvement in PFS in Chinese [patients with] NSCLC,” Frank Jiang, MD, PhD, chairman and CEO of CStone Pharmaceuticals, stated in a press release. “It has the potential of becoming the world’s first anti–PD-L1 monoclonal antibody that can be combined with chemotherapy as the first-line treatment of [patients with] squamous and nonsquamous NSCLC. This further strengthens our confidence in the development of CS1001 and greatly expediate CStone’s commercialization progress.”
The investigational anti–PD-L1 monoclonal antibody was discovered by CStone Pharmaceuticals using the OmniRat® transgenic animal platform developed by Ligand Pharmaceuticals. CS1001 reflects the natural IgG4 human antibody, which can decrease the risk of immunogenicity and potential adverse effects in patients.
In the multicenter, randomized, double-blind phase 3 CS1001-302 trial, investigators set out to evaluate the safety and efficacy of CS1001 in combination with platinum-based chemotherapy compared with placebo plus platinum-based chemotherapy in treatment-naïve patients with stage IV NSCLC.
To be eligible to participate on the trial, patients had to be between the ages of 18 and 75 years, had to have histologically or cytologically confirmed stage IV disease, a measurable target lesion assessed by investigators in accordance with RECIST v1.1 criteria, an ECOG performance status of 0-1, and a life expectancy of 12 weeks or more.2 Notably, patients could not have received any systemic treatment for advanced or metastatic disease.
Moreover, patients with histologically confirmed small cell lung cancer, with current active autoimmune disease or a previous history of autoimmune disease, with malignancies other than NSCLC within 5 years before randomization, or with a known history of human immunodeficiency virus, were not permitted to enroll on the trial. Patients with hepatitis B or C, a known history of alcoholism or drug abuse, a known hypersensitivity to any component of the study treatment, or with any other conditions that might influence compliance, were also not able to participate.
In the trial, patients on the experimental arm received CS1001 at 1200 mg via intravenous infusion every 3 weeks for up to 24 months, as well as carboplatin on day 1 of each 21-day treatment cycle, pemetrexed on day 1 of each 21-day cycle, and paclitaxel on day 1 of each 21-day cycle. Patients on the control arm received placebo plus the same schedule of chemotherapy as those in the experimental arm.
The primary end point of the trial was PFS in patients with PD-L1 expression of 1% or more and PFS in all patients assessed by investigators in accordance with RECIST v1.1.
“Compared with published results of other anti–PD-1/PD-L1 monoclonal antibodies in combination with chemotherapy in first-line NSCLC trials, the CS1001-302 study, with an innovative design, is the first phase 3 clinical study in China for the first-line treatment of both squamous and nonsquamous NSCLC subtypes,” said Jason Yang, MD, PhD, chief medical officer of CStone, added in the release. “We will continue to make every effort to promote and more extensively evaluate the potential clinical benefit of this product in patients with hematologic malignancies, stage III NSCLC, advanced gastric cancer, liver cancer, and esophageal cancer.”
A phase 1 dose-escalation trial with CS1001 was previously completed in China. During the phase 1a and 1b portions of the trial, the agent demonstrated encouraging antitumor activity and tolerability in several tumor types.
CS1001 is currently under investigation in several ongoing trials. The agent is being looked at in a phase 1 bridging study in the United States, and the clinical program in China comprises 1 multiarm phase 1b study examining CS1001 in several tumor types. Additionally, 2 phase 2 registrational trials are evaluating CS1001 in lymphoma, and 4 phase 3 trials registrational trials are evaluating the agent’s use in stage III/IV NSCLC, gastric cancer, and esophageal cancer.