The anti–PD-1 agent tislelizumab (BGB-A317) in combination with chemotherapy improved progression-free survival compared with chemotherapy alone as a first-line treatment for patients with advanced squamous non–small cell lung cancer.
The anti—PD-1 agent tislelizumab (BGB-A317) in combination with chemotherapy improved progression-free survival (PFS) compared with chemotherapy alone as a first-line treatment for patients with advanced squamous non–small cell lung cancer (NSCLC), meeting the primary endpoint at a planned interim analysis of the phase III BGB-A317-307 trial (NCT03594747).1
The analysis, which was conducted by an independent review committee (IRC), showed that tislelizumab in combination with either carboplatin/paclitaxel or with carboplatin/nab-paclitaxel (Abraxane) crossed the prespecified efficacy boundary compared with carboplatin/paclitaxel alone.
Regarding safety, the safety profile for tislelizumab with either chemotherapy regimen was found to be consistent with the known risks of each study treatment and no new safety signals were identified.
Full findings will be presented at an upcoming medical meeting. Additionally, BeiGene, the developer of tislelizumab, stated in a press release that it anticipates discussing its plans to file a supplemental new drug application (sNDA) for tislelizumab as a first-line treatment for patients with squamous NSCLC with the Center for Drug Evaluation (CDE) at the National Medical Products Administration (NMPA) in China.
“Squamous NSCLC remains a significant unmet need, representing approximately 30% of patients with NSCLC in China,” lead study investigator Jie Wang, MD, a professor at the Cancer Hospital Chinese Academy of Medical Sciences, stated in the press release. “This phase III study was designed to assess the impact of tislelizumab given in combination with chemotherapy as a potential treatment to improve outcomes in patients with advanced squamous NSCLC, for whom prognoses are typically quite poor. These results give us hope that we could have a new treatment option for these patients.”
Tislelizumab is a humanized IgG4 PD-1-directed monoclonal antibody specifically designed to minimize binding to FcγR on macrophages, BeiGene stated in the press release. The company added that preclinical data have shown that binding to FcγR on macrophages compromises the antitumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T-effector cells.
In the multicenter, open-label, randomized, phase III BGB-A317-307 trial, the efficacy and safety of tislelizumab combined with either carboplatin/paclitaxel or carboplatin/nab-paclitaxel was compared with carboplatin/paclitaxel alone in 360 patients from mainland China with untreated stage IIIb/IV squamous NSCLC, regardless of PD-L1 expression. Patients were randomized in a 1:1:1 fashion and tislelizumab was administered at 200 mg every 3 weeks in combination with the chemotherapy regimens until disease progression, unacceptable toxicity, physician consent, or withdrawal.
Patients who were on the chemotherapy-only arm and experienced disease progression, verified by central independent review, were permitted to cross over to receive single-agent tislelizumab.
To be eligible for enrollment, patients must have been between 18 and 75 years old, had advanced NSCLC with squamous histology, an ECOG performance status ≤1, at least 1 measurable lesion, did not previously receive treatment for locally advanced or metastatic squamous disease, had a life expectancy ≥12 weeks, and had adequate organ function. Patients could not have a history of interstitial lung disease, HIV infection, active or a history of autoimmune disease, clinically significant pericardial effusion, or have had severe infections, active leptomeningeal disease, or uncontrolled or untreated brain metastasis. Moreover, patients could not have EGFR or ALK abnormalities, nor could they have received prior systemic treatment with EGFR, ALK, or PD-1/PD-L1 inhibitors.
The primary endpoint is PFS per IRC; key secondary endpoints include objective response rate (ORR), duration of response, overall survival, and safety.
An ongoing phase II trial is evaluating tislelizumab with platinum-based chemotherapy as a first-line treatment for Chinese patients with advanced lung cancer (NCT03432598). Patients with nonsquamous disease received tislelizumab with pemetrexed plus platinum-based therapy followed by pemetrexed maintenance; those with squamous disease received tislelizumab with paclitaxel/platinum-based therapy or with gemcitabine/platinum-based therapy. Patients with small cell lung cancer (SCLC) received tislelizumab with etoposide and platinum-based therapy.
As of October 15, 2018, 54 patients had received tislelizumab and 24 remained on treatment. Preliminary data showed that the ORR was 67%, which comprised 36 partial responses, most of which occurred within the first 2 assessments.2 Thirteen patients had stable disease, 2 had progressive disease, and 3 missed their first assessment. In the nonsquamous (n = 16), squamous with paclitaxel/platinum-based therapy (n = 15), squamous with gemcitabine/platinum-based therapy (n = 6), and SCLC (n = 17) groups, the ORRs were 44%, 80%, 67%, and 77%, respectively.
Additionally, grade ≥3 adverse events (AEs) occurring in >15% of patients included decreased neutrophil counts (n = 25) and anemia (n = 9). Immune-related AEs, which occurred in ≥2 patients, included decreased triiodothyronine, hyperthyroidism, hypothyroidism, and pyrexia (n = 2 each). There was 1 patient with squamous NSCLC who experienced fatal myocarditis/myositis after 1 cycle of treatment. However, other AEs resolved with interruption of tislelizumab (n = 30), discontinuation (n = 4), or other appropriate treatment.
“Tislelizumab was recently approved in China for patients with relapsed or refractory classical Hodgkin lymphoma, and we have a broad development program with more than 5000 patients enrolled in over 25 tislelizumab studies, including 15 potentially registration-enabling trials,” Yong (Ben) Ben, MD, chief medical officer, Immuno-Oncology at BeiGene, stated in the press release. “We are extremely excited about the compelling results that tislelizumab demonstrated in this phase III trial and for its potential use as a first-line treatment for patients in China with advanced squamous NSCLC. We look forward to continuing the development program for tislelizumab in lung cancer, which includes 3 other phase III trials, and reporting additional data.”
Currently, tislelizumab is approved by the China NMPA as a treatment for patients with classical Hodgkin lymphoma who received ≥2 prior therapies. Moreover, the CDE at the NMPA granted a priority review designation to an sNDA for tislelizumab in patients with previously treated locally advanced or metastatic urothelial carcinoma.