Tislelizumab Receives CHMP Recommendation for First- and Second-Line Treatment of NSCLC


The European Medicines Agency’s CHMP has recommended the approval of tislelizumab in the first- and second-line for non–small cell lung cancer.

Mark Lanasa, MD, PhD

Mark Lanasa, MD, PhD

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of tislelizumab (Tevimbra) across 3 indications for the first- and second-line treatment of patients with non–small cell lung cancer (NSCLC).1

The humanized IgG4 anti–PD-1 monoclonal antibody is currently under investigation in the phase 3 RATIONALE-307 (NCT03594747), RATIONALE-304 (NCT03663205), and RATIONALE-303 (NCT03358875) trials. Clinical data from these trials supported the positive opinion from the regulatory committee.1

Data from RATIONALE-307 support the first indication for tislelizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel (Abraxane) in the first-line treatment of patients with locally advanced or metastatic squamous NSCLC. who are not candidates for surgical resection or platinum-based chemoradiation, and those with metastatic NSCLC.

The second indication is based on the RATIONALE-304 trial of tislelizumab in combination with pemetrexed (Alimta) and platinum-containing chemotherapy. This indication is for the first-line treatment of adult patients with locally advanced or metastatic nonsquamous NSCLC whose tumors have PD-L1 expression on 50% or more of tumor cells with no EGFR- or ALK-positive mutations. Both indications state that patients with locally advanced disease cannot be candidates for surgical resection or platinum-based chemoradiation.1

Second-line monotherapy results from RATIONALE-303 support the third potential indication for tislelizumab in adult patients with locally advanced or metastatic NSCLC following prior platinum-based therapy. Patients with EGFR-mutant or ALK-positive disease should have received targeted therapies before receiving tislelizumab.1

“Through 3 phase 3 clinical trials enrolling nearly 1,500 patients across the world including in the European Union, tislelizumab has been shown to be an effective therapy for patients with treatment-naive and treatment-resistant NSCLC,” Mark Lanasa, MD, PhD, chief medical officer of Solid Tumors at BeiGene, said in a press release. “Today’s positive CHMP opinion brings us one step closer to providing an important treatment option to patients in Europe with lung cancer, which is among the most common cancers and a leading cause of cancer death in the region.”

Findings from the RATIONALE-304 and RATIONALE-303 studies were separately published in the Journal of Thoracic Oncology, and data from the RATIONALE-307 trial were published in JAMA Oncology.1


RATIONALE-307 is an open-label, randomized phase 3 trial investigating the use of first-line tislelizumab plus chemotherapy in 360 patients with advanced squamous NSCLC. Notably, RATIONALE-307 achieved its primary end point of significantly improved progression-free survival (PFS) with the combination vs standard-of-care chemotherapy in 2021. Higher objective response rates (ORRs) were also observed with the combination vs chemotherapy in addition to a manageable safety and tolerability profile, irrespective of PD-L1 expression.1,2

The median PFS was 7.7 months with tislelizumab and paclitaxel/carboplatin (HR for the combination vs chemotherapy alone, 0.45; 95% CI, 0.326-0.619; P < .001) and 9.6 months for the tislelizumab and nab-paclitaxel/carboplatin combination (HR for the combination vs chemotherapy alone, 0.43; 95% CI, 0.308-0.60; P < .001), compared with 5.5 months for paclitaxel/carboplatin alone. Median follow-up was 8.6 months. The most common grade 3 or higher treatment-emergent adverse effects (TEAEs) included decreased neutrophil levels, neutropenia, and leukopenia.1

Eligible patients must have received a diagnosis of untreated, advanced NSCLC and have an ECOG performance status of 1 or less; 1 or more measurable lesions; a life expectancy greater than 12 weeks; and adequate organ function. Key exclusion criteria included the presence of EGFR or ALK mutations; prior systemic anticancer therapy; prior therapies targeting PD-(L)1; a history of interstitial lung disease (ILD); pericardial effusion; severe infections; or a major surgical procedure before randomization.3


The open-label, randomized phase 3 RATIONALE-304 trial evaluated 334 patients with locally advanced or metastatic nonsquamous NSCLC. These patients were treated with tislelizumab plus carboplatin or cisplatin and pemetrexed vs chemotherapy alone.1

The study achieved its primary end point, demonstrating a statistically significant PFS benefit with first-line tislelizumab and chemotherapy vs chemotherapy alone (HR, 0.65; 95% CI, 0.47-0.91; P = .0054), as well as increased response rates and prolonged response duration.1

At a median follow-up of 9.8 months, the median PFS in the overall population was 9.7 months for the tislelizumab combination groups vs 7.6 months with platinum and pemetrexed alone. In the PD-L1 greater than 50% group, median PFS was 14.6 months with tislelizumab plus chemotherapy vs 4.6 months with chemotherapy alone (stratified HR, 0.31; 95% CI, 0.178-0.547). The most common grade 3 or higher TEAEs were predominantly associated with chemotherapy and included neutropenia and leukopenia.1

Eligibility criteria for the study included a diagnosis of advanced NSCLC; an ECOG performance status of 1 or less; at least one measurable lesion per RECIST v1.1 criteria; no prior systemic chemotherapy for advanced or metastatic nonsquamous NSCLC; a life expectancy of at least 12 weeks; and adequate organ function.4

Exclusion criteria include expression of an EGFR-sensitizing mutation or ALK gene translocation; any prior systemic anticancer therapy administered 28 days before the start of the study treatment; prior treatment with EGFR or ALK inhibitors; previous PD(L)-1 inhibition; a history of ILD, non-infectious pneumonitis or uncontrolled systemic diseases; clinically significant pericardial effusion; severe infections; active leptomeningeal disease or uncontrolled, untreated brain metastasis; and any major surgical procedure within 28 days prior to randomization.4

Notably, the China National Medical Products Administration accepted a supplemental new drug application for tislelizumab in combination with chemotherapy for the frontline treatment of these patients in 2020.5


The open-label, randomized phase 3 RATIONALE 303 study compared tislelizumab with docetaxel in 805 patients with advanced NSCLC who experienced progression on prior platinum-based chemotherapy. The trial achieved its primary end point, with second- or third-line tislelizumab producing a statistically significant and clinically meaningful OS benefit compared with docetaxel in the intent-to-treat population (HR, 0.66; 95% CI, 0.56-0.79; P < .0001), regardless of PD-L1 expression.1,6

The median OS was 16.9 months for patients treated with tislelizumab vs 11.9 months for those treated with docetaxel. Upon final analysis, the median OS in the PD-L1–positive patient population favored tislelizumab at 19.3 months vs 11.5 months with docetaxel (HR, 0.53; 95% CI, 0.41-0.70; P < .0001). The most frequently documented grade 3 or greater TEAEs included pneumonia, anemia, and dyspnea.1

Ongoing Investigations of Tislelizumab

Neoadjuvant tislelizumab is also being evaluated along with platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab. This regimen led to a significant improvement in event-free survival vs neoadjuvant placebo plus platinum-based doublet chemotherapy followed by surgery and adjuvant placebo in resectable NSCLC. These outcomes were observed in the phase 3 RATIONALE-315 trial (NCT04379635) and presented during the February ESMO Virtual Plenary.7

“As we strengthen our global portfolio in solid tumors, this positive CHMP opinion marks another significant milestone in the European Union for tislelizumab only a few months after it was approved for the treatment of advanced esophageal squamous cell carcinoma,” Lanasa concluded. “We will continue to follow the science and data to advance tislelizumab as a monotherapy and combination treatment to address unmet needs of patients across the world.”


  1. BeiGene receives positive CHMP opinion for tislelizumab as treatment for non-small cell lung cancer. News release. BeiGene. February 26, 2024. Accessed February 26, 2024.
  2. Wang J, Lu S, Yu X, et al. Tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for advanced squamous non–small-cell lung cancer. JAMA Oncol. 2021;7(5):709-717. doi:10.1001/jamaoncol.2021.0366
  3. A study of tislelizumab in combination with chemotherapy versus chemotherapy in advanced lung cancer. ClinicalTrials.gov. Updated October 17, 2023. Accessed February 26, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03594747
  4. A study evaluating the efficacy and safety of tislelizumab versus chemotherapy in advanced non-squamous NSCLC. ClinicalTrials.gov. Updated May 5, 2023. Accessed February 26, 2024. https://clinicaltrials.gov/study/NCT03663205
  5. BeiGene announces acceptance of a supplemental new drug application for tislelizumab in combination with chemotherapy in first-line advanced non-squamous non-small cell lung cancer in China. News release. June 19, 2020. Accessed February 26, 2024. https://ir.beigene.com/news/beigene-announces-acceptance-of-a-supplemental-new-drug-application-for-tislelizumab-in-combination-with-chemotherapy/a57cd4de-e41f-48c5-b287-0c60fb55e2f9/
  6. Comparison of efficacy and safety of anti-PD-1 antibody BGB-A317 versus docetaxel as treatment in the second- or third-line setting in participants with NSCLC. ClinicalTrials.gov. Updated February 5, 2024. Accessed February 26, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03358875
  7. Yue D, Wang W, Liu H, et al. RATIONALE-315: event-free survival (EFS) and overall survival (OS) of neoadjuvant tislelizumab (TIS) plus chemotherapy (CT) with adjuvant TIS in resectable non-small cell lung cancer (NSCLC). . 2024;35(3):P332-333. doi:10.1016/j.annonc.2024.01.005
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