Adding Beigene‘s experimental therapy tislelizumab to standard first-line chemotherapy significantly delays disease progression or death in patients with advanced squamous non-small cell lung cancer (NSCLC), data from a Phase 3 clinical trial shows.
The combination also increased the proportion of patients responding to treatment and the duration of such responses, compared to chemotherapy only.
The findings were presented at the 2020 American Society of Clinical Oncology (ASCO) annual meeting — held virtually due to the COVID-19 pandemic — in the poster “Phase 3 study of tislelizumab plus chemotherapy vs chemotherapy alone as first‑line (1L) treatment for advanced squamous non‑small cell lung cancer (sq NSCLC).”
Tislelizumab belongs to a class of immunotherapies called immune checkpoint inhibitors. It binds to PD-1, a receptor expressed at the surface of immune cells that is sometimes hijacked by cancer cells to dampen immune responses. PD-1 inhibitors reactivate the immune system against the tumor.
Tislelizumab is different from other PD-1 antibodies because it has an engineered region that minimizes its interaction with other immune cells, which is thought to reduce adverse events (side effects).
The multi-center, randomized, open-label Phase 3 clinical trial (NCT03594747) was conducted in China and sought to compare the effectiveness and safety of tislelizumab plus standard chemotherapy versus chemotherapy alone as first-line treatment for advanced squamous NSCLC.
“Lung cancer is the leading cause of cancer-related death in China, and with NSCLC comprising the most common form of the disease, it is critical to identify new treatments that address patient needs,” Jie Wang, MD, PhD, said in a press release. Wang is with the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
The trial enrolled 360 patients with advanced NSCLC who were assigned randomly to one of three treatment groups: tislelizumab in combination with paclitaxel and carboplatin (group A, 120 patients); tislelizumab plus Abraxane (nab-paclitaxel) and carboplatin (group B, 119 patients); or paclitaxel and carboplatin (group C, 121 patients).
Chemotherapy was administered for four to six cycles cycles and tislelizumab was given intravenously (into-the-vein) at a 200 mg dose every three weeks. Patients were kept on their assigned regimen until disease progression, unacceptable toxicity, physician decision, or consent withdrawal.
The trial’s main goal was to determine whether the tislelizumab combinations in groups A and B extended the time patients lived without disease worsening compared to group C. Additional goals included objective response rate, or the proportion of patients with meaningful reductions in tumor size, duration of response, and overall survival.
At the time of the analysis (Dec. 6, 2019), 63 patients (52.5%) in group A and 66 patients (55.5%) in group B were still receiving treatment. Also, 81 patients (66.9%) had completed chemotherapy in group C.
An assessment by an independent review committee showed that patients on tislelizumab lived significantly longer without signs of disease progression (7.6 months on both groups A and B), than those on chemo only (5.5 months).
The benefits were seen regardless of PD-L1 expression, which often is seen as a biomarker of responses to immune checkpoint inhibitors like tislelizumab.
Response rates also were better with tislelizumab — 73% in group A and 75% in group B, compared with 50% in group C — as were duration of responses, which nearly doubled in groups A (8.2 months) and B (8.6 months), compared with the 4.2 months in group C.
To date, the median number of treatment cycles were comparable across groups, but differences in overall survival could not be assessed yet.
“The results from this Phase 3 trial demonstrated that inhibiting the PD-1 pathway with tislelizumab, combined with standard chemotherapy, provided a clinically meaningful benefit to patients with advanced squamous NSCLC, as assessed by progression-free survival and response rates,” Wang said.
The tislelizumab-chemo combos were generally well-tolerated and consistent with the known safety profiles of tislelizumab, chemotherapy, and the disease itself. No new safety signals were identified.
Most treatment-related adverse events (AEs) were mild or moderate in severity. The most common AEs were blood-related, including anemia, hair loss, decreased appetite, and low levels of immune cells such as neutrophils, leukocytes, and white blood cells.
Serious AEs related to treatment were recorded in 27 patients in group A, and 28 in group B, and in 17 patients in group C. These adverse events led to the death of four patients (3.3%) in group A, five patients (4.2%) in group B, and five patients (4.3%) in group C.
Tislelizumab, approved in China for treating lymphoma and bladder cancer patients, also has shown benefits, alone and in combination with standard chemo regimens, in other types of tumors, including stomach and esophageal cancer, and nasopharyngeal cancer.
Beigene recently submitted an application to the China National Medical Products Administration asking for tislelizumab’s approval in combination with chemotherapy for the first-line treatment of non-squamous NSCLC. The recent findings in squamous NSCLC patients also were included in the filling, potentially making tislelizumab available to a large population of patients.
“Together with the positive results we recently announced for a second Phase 3 trial in first-line NSCLC in patients with non-squamous histology, we believe these important findings position tislelizumab to serve the large population of patients in China with advanced NSCLC, for whom we hope to bring a new treatment option as quickly as possible,” said Yong (Ben) Ben, MD, chief medical officer, immuno-oncology at BeiGene.