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David S. Ettinger, MD, FACP, FCCP

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ESMO 2022: Novel Bispecific Antibody Plus Chemotherapy Under Study in NSCLC

By: Julia Fiederlein
Posted: Friday, September 30, 2022

According to Myung-Ju Ahn, MD, PhD, of Sungkyunkwan University School of Medicine, Seoul, Korea, and colleagues, carboplatin plus pemetrexed in combination with 1,500 mg of the PD-1/CTLA-4 bispecific antibody MEDI5752 prolonged the durations of response, progression-free survival, and overall survival compared with pembrolizumab in treatment-naive patients with nonsquamous non–small cell lung cancer (NSCLC). Findings from this ongoing phase Ib/II trial, which were presented during the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract LBA56), revealed anticancer activity and improved tolerability with 750 mg of MEDI5752.

In the randomized cohort (n = 41), patients were administered four cycles of carboplatin plus pemetrexed followed by maintenance therapy with pemetrexed plus either 1,500 mg of MEDI5752 every 3 weeks or pembrolizumab. Subsequently, patients in the single arm-cohort (n = 50) received 750 mg of MEDI5752 every 3 weeks in combination with carboplatin plus pemetrexed.

The median durations of response, progression-free survival, and overall survival were prolonged with 1,500 mg of MEDI5752 compared with pembrolizumab in the intention-to-treat population and in those with PD-L1 expression less than 1%. The rates of grade 3 treatment-related adverse events and subsequent discontinuations were both 70% with 1,500 mg of MEDI5752, and thus the investigators explored this agent at a lower dose.

Treatment with 750 mg of MEDI5752 demonstrated objective response rates of 44% and 48% in the intention-to-treat population and in those with PD-L1 expression less than 1%, respectively, at a median follow-up of approximately 3.9 months. An improved safety profile was reported (grade 3 treatment-related adverse events: 32%; subsequent treatment discontinuation: 20%). In both cohorts, treatment with MEDI5752 was found to increase T-cell proliferation (and clonal expansion with 1,500 mg) compared with pembrolizumab; these findings seemed to be consistent with the pharmacodynamic effects of CTLA-4 blockade.

Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.


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