Bintrafusp Alfa Shows Similar Efficacy to Pembrolizumab in PD-L1-High/Advanced NSCLC


No significant difference in efficacy outcomes were shown with bintrafusp alfa vs pembrolizumab in patients with PD-L1-high, advanced non–small cell lung cancer. However, further investigation may offer more information about the benefit of this drug class.

Edward Garon, MD, MS

Edward Garon, MD, MS

Exploration of first-line treatment with bintrafusp alfa (M7824) in patients with PD-L1-high, advanced non–small cell lung cancer (NSCLC) did not result in improved efficacy compared with first-line treatment with pembrolizumab (Keytruda), according to published findings from a phase 3 study (NCT03631706).1

For the treatment of PD-L1-high, advanced NSCLC, in the frontline setting, FDA-approved agents include pembrolizumab, atezolizumab (Tecentriq), and cemiplimab (Libtayo). These drugs have a median overall survival of 20 months or more. However, many patients develop resistance to anti-PD-L1 agents, which calls for novel treatment mechanisms.

"Although there are many patients who do develop long-term benefit with these drugs, most people actually do not obtain an objective response, and even among those who do achieve an objective response, they often do not derive long-term disease control," Edward B. Garon, MD, MS, professor of medicine at UCLA Health told Targeted OncologyTM.

Bintrafusp alfa is a multi-functional drug which targeted PD-L1 and TGF-β. The drug was investigated in the global, randomized, open-label, phase 3 trial of patients with PD-L1-high, advanced NSCLC based on prior phase 1 data, which showed that bintrafusp alfa achieved a high objective response rate (ORR) in patients with ≥ 80% PD-L1 positivity.

Lung cancer, medically 3D illustration on light background | Image Credit: © Axel Kock -

Cancer of the lung | Image Credit: © Axel Kock -

A total of 304 patients with randomized 1:1 in the study to receive bintrafusp alfa 1200 mg, every 2 weeks or pembrolizumab 200 mg, every 3 weeks. Both therapies were administered until confirmed disease progression, unacceptable toxicity, or until patients reached 24 weeks of treatment.

At a median follow-up of 14.3 months (95% CI, 13.1-16.0 months) in the bintrafusp alfa and 14.5 months (95% CI, 13.1-15.9 months) in the pembrolizumab arm, the median progression-free survival (PFS) by independent review committee assessment was 7.0 months (95% CI, 4.2 months to not reached [NR]) compared with 11.1 months (95% CI, 8.1-NR) with pembrolizumab (HR, 1.232; 95% CI, 0.885-1.714; P =.89). PFS by investigator assessment was similar.

The median overall survival (OS) with bintrafusp alfa was not significantly different compared with pembrolizumab. The median OS observed was 21.1 months (95% CI, 21.1 months-NR) with bintrafusp alfa vs 22.1 months (95% CI, 20.4 months-NR) with pembrolizumab (HR, 1.201; 95% CI, 0.796-1.811; P =.81).

Bintrafusp alfa also demonstrated an unconfirmed objective response rate of 46.7% (95% CI, 38.6%-55.0%) vs 51.3% (95% CI, 43.1%-59.5%; P =.041). The median duration of response was not reached in either arm.

Although higher rates of adverse events (AEs) were seen in the bintrafusp alfa arm, leading to a higher number of patients discontinuing treatment, the safety profile was manageable. Treatment-related AEs (TRAEs) occurred in 82.1% of the bintrafusp alfa arm vs 69.1% of the pembrolizumab arm, and these TRAEs were grade 3/4 in 42.4. vs 13.2%, respectively.

The most common TRAEs observed with bintrafusp alfa treatment were pruritus (31.8%), rash (29.1%), diarrhea (12.6%), rash maculopapular (11.3%), 396 aspartate aminotransferase increased (11.3%), asthenia (11.3%), fatigue (11.3%), 397 anemia (10.6%), and hypothyroidism (10.6%). In comparison, the most common TRAES observed with pembrolizumab were pruritus (25.7%), rash (13.2%), and hypothyroidism (13.2%). Serious TRAEs occurred in 27.2% of the bintrafusp alfa arm compared with 11.8% of the pembrolizumab arm.

The occurrence of TRAEs led to death in 0.7% of the bintrafusp alfa compared with 1.3% of the pembrolizumab arm. Further, 25.8% of the bintrafusp alfa discontinued treatment due to TRAEs compared with 6.6% of the pembrolizumab arm.

Among patients treated with bintrafusp alfa, AEs of special interest were higher than in the pembrolizumab arm (53.0% v 34.9%).

"Despite the negative result, I think that more data is needed before empirically targeting TGF-beta in a large population of unselected patients or patients selected based on only PD-L1 expression level," said Garon.


Cho BC, Lee JS, Wu YL, et al. Bintrafusp alfa versus pembrolizumab in patients with treatment-naive, PD-L1–high advanced non-small cell lung cancer: a randomized, open-label, phase 3 trial. J Thorac Oncol. published August 17, 2023. doi:10.1016/j.jtho.2023.08.018.

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