Tislelizumab Frontline Combo Improves PFS in Nonsquamous NSCLC

The PD-1 inhibitor tislelizumab combined with frontline chemotherapy significantly improved progression-free survival versus chemotherapy alone in patients with nonsquamous non–small cell lung cancer.

The PD-1 inhibitor tislelizumab combined with pemetrexed (Alimta) and platinum chemotherapy significantly improved progression-free survival (PFS) versus chemotherapy alone in the frontline setting for the treatment of patients with nonsquamous non—small cell lung cancer (NSCLC), meeting the primary endpoint of the phase III BGB-A317-304 trial.1

BeiGene, the China-based developer of tislelizumab, reported in a press release the no new safety signals emerged with the study treatments compared with the established toxicity profile for each agent. The company plans to present the findings from BGB-A317-304 at a future medical meeting and discuss logistics with Chinese regulatory authorities for submitting a supplemental application to market tislelizumab in this setting.

The open-label, multicenter phase III BGB-A317-304 trial (NCT03663205) included 334 patients with previously untreated stage IIIb or stage IV nonsquamous NSCLC whose tumors did not harbor EGFR mutations or ALK translocations. Patients were randomized in a 2:1 ratio to tislelizumab at 200 mg every 3 weeks combined with pemetrexed and investigator’s choice of platinum chemotherapy (carboplatin or cisplatin), or the control arm of pemetrexed and platinum chemotherapy alone.

PFS per the evaluation of an independent review committee was the primary endpoint. Overall survival (OS) and safety were secondary endpoints.

“We are excited to announce the positive outcome in the interim analysis of this phase III study of tislelizumab in first-line nonsquamous NSCLC, following the positive interim analysis in first-line squamous NSCLC earlier this year,” Yong (Ben) Ben, MD, chief medical officer, Immuno-Oncology at BeiGene, stated in the press release. “These results add to our growing body of evidence demonstrating the efficacy and safety of tislelizumab for the treatment of advanced cancers. We look forward to continuing to evaluate tislelizumab in more than 25 studies, including 15 potentially registration-enabling trials.”

BeiGene previously reported in January 2020 that tislelizumab in combination with chemotherapy improved PFS compared with chemotherapy alone as a first-line treatment for patients with advanced squamous NSCLC, meeting the primary endpoint at a planned interim analysis of the phase III BGB-A317-307 trial (NCT03594747).2 The analysis, which was conducted by an independent review committee, 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.

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. BeiGene plans to present the study findings at an upcoming medical meeting and file for approval with Chinese regulatory authorities to market tislelizumab in this setting.

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.

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.3 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 is currently approved in China as a treatment for patients with classical Hodgkin lymphoma who received at least 2 prior therapies, as well as for patients with locally advanced or metastatic urothelial carcinoma with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.


  1. BeiGene Announces that the Phase 3 Trial of Tislelizumab Combined with Chemotherapy in Patients with First-Line Non-Squamous Non-Small Cell Lung Cancer Met the Primary Endpoint of Progression-Free Survival at Interim Analysis. Published April 13, 2020. https://bit.ly/3b9FrKY. Accessed April 13, 2020.
  2. BeiGene announces that the phase 3 clinical trial of its anti-pd-1 antibody tislelizumab in patients with first-line squamous non-small cell lung cancer met the primary endpoint of progression-free survival at interim analysis [news release]: Beijing, China and Cambridge, MA. Published January 21, 2020. https://yhoo.it/38q8ubb. Accessed April 14, 2020.
  3. Wang J, Zhao J, Wang Z, et al. Tislelizumab, an investigational anti-PD-1 antibody, combined with chemotherapy as first-line treatment for lung cancer in Chinese patients. J Clin Oncol. 2019;37(suppl_15): doi: 10.1200/JCO.2019.37.15_suppl.e14067.


“NSCLC is a debilitating disease that comprises approximately 85% of lung cancer cases globally. It is estimated that approximately 60 percent of lung cancer diagnoses are made when the disease is in advanced stages and patients need more treatment options. The positive outcome at interim analysis for tislelizumab in this study and in other clinical trials, including for first-line squamous NSCLC, demonstrate that it is a promising option for people living with this advanced cancer,” lead study investigator Shun Lu, MD, professor at Shanghai Chest Hospital, Jiao Tong University, stated in the press release.