CS1001 Plus Chemotherapy Prolongs Progression-Free Survival in Stage IV NSCLC

The combination of CS1001 and chemotherapy led to an improvement in progression-free survival (PFS) among patients with stage IV squamous and non-squamous non–small cell lung cancer (NSCLC), according to data from the phase 3 CS1001-302 clinical trial assessed by an Independent Data Monitoring Committee, achieving the study’s primary end point.¹

The results were announced in press release from CStone Pharmaceuticals. Based on the results, the submission of a New Drug Application is being considered.

“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 non-squamous NSCLC subtypes. We will continue to make every effort to promote and more extensively evaluate the potential clinical benefit of this product in patients with hematological malignancies, stage III NSCLC, advanced gastric cancer, liver cancer, and esophageal cancer,” said Jason Yang, chief medical officer, Cstone.

The study population was compiled of 480 patients who were randomized to receive either CS1001 in a 1200 mg dose plus either carboplatin, paclitaxel, or pemetrexed or placebo plus chemotherapy in the comparator arms. The study is also exploring overall survival, PFS, and safety as secondary end points.

Overall, the median PFS was 7.8 months in the CS1001 plus chemotherapy arm compared with 4.9 months in the placebo arm (HR, 0.50; 95% CI, 0.39-0.64; P <.0001) per investigator assessment. The reduction in the risk of disease progression or death was 50%. The clinical benefit observed with the CS1001 combination was consistent across the subgroups in the study, as well as in patients with different PD-L1 expression levels. Data were confirmed by a Blinded Independent Central Review.

In terms of safety, the combination was well-tolerated. No new safety signals were observed in the study.

To be included in the study, patients aged 18 to 75 years were required to have histologically or cytologically confirmed stage IV NSCLC, a measurable target lesion, an ECOG performance status of 0 to 1, a life expectancy of at least 12 weeks, and adequate organ function. Patients could not have received prior systemic treatment for metastatic disease.

CS1001 is an investigational anti-PD-L1 monoclonal antibody. The agent first showed promises in a phase 1a/1b clinical trial (NCT03312842) in which the drug in combination with platinum-based chemotherapy achieved anti-tumor responses and tolerable safety.²

Results were presented during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. Patients with non-squamous disease received CS1001 1200 mg for 4 to 6 cycles in combination with either carboplatin or pemetrexed, followed by pemetrexed maintenance. The same treatment was given to patients who had squamous disease, except the pemetrexed maintenance. Instead, patients with squamous NSCLC received CS1001 maintenance.

Twenty-one patients with non-squamous NSCLC were followed for a median duration of 135 days. The objective response rate (ORR)f in this cohort was 47.6%, which were all partial responses (PRs). In addition, 42.9% of patients had stable disease (SD) and 9.5% had progressive disease (PD). The disease control rate (DCR) observed in the non-squamous cohort was 90.5%.

Median follow up in the squamous NSCLC cohort was 109 days. The ORR observed with CS1001 plus platinum-based chemotherapy was 58.5%, which were all PRs. SD was observed in 41.2% of patients and no patients had PD. The DCR in this cohort was 100%.

Overall, CS1001-related adverse events occurred in 85.7% of the non-squamous cohort and 90.0% of the squamous cohort and immune-related adverse events occurred in 5 and 3 patients, respectively.

“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 non-squamous NSCLC subtypes. We will continue to make every effort to promote and more extensively evaluate the potential clinical benefit of this product in patients with hematological malignancies, stage III NSCLC, advanced gastric cancer, liver cancer, and esophageal cancer,” stated Jason Yang, PhD, CEO of CStone.

_References:

_{1. CStone announces that omniab-derived cs1001 (anti-pd-l1) phase 3 trial met the primary endpoint as first-line treatment in stage iv squamous and non-squamous non-small cell lung cancer and announces plans to submit a New Drug Application. News release. August 7, 2020. Accessed August 7, 2020. https://bwnews.pr/31yEQit}

_{2. Zhou Q, Zhang Q, Xu N, et al. Platinum-based chemotherapy (chemo) with CS1001, an anti-PD-L1 antibody, for first-line advanced non-small cell lung cancer (NSCLC): Preliminary results from phase Ib cohorts of CS1001-101 study. J Clin Oncol. 2020: 38 (suppl; abstr e21687). doi: 10.1200/JCO.2020.38.15_suppl.e21687}