Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC

Abstract

Introduction: Data of first-line ramucirumab plus pembrolizumab treatment of programmed death-ligand 1 (PD-L1)positive NSCLC (cohort E) are reported (NCT02443324). Methods: In this multicenter, open-label phase 1a/b trial, patients received ramucirumab 10 mg/kg and pembrolizumab 200 mg every 21 days for up to 35 cycles. PD-L1 positivity was defined as tumor proportion score (TPS) greater than or equal to 1%. Exploratory NanoString biomarker analyses included three T-cell signatures (T-cellinflamed, Gajewski, and effector T cells) and CD274 gene expression. Results: Cohort E included 26 patients. Treatment-related adverse events of any grade occurred in 22 patients (84.6%). Treatment-related adverse events of grade greater than or equal to 3 were reported in 11 patients (42.3%); the most frequent was hypertension (n ¼ 4, 15.4%). Objective response rate was 42.3% in the treated population and 56.3% and 22.2% for patients with high (TPS ! 50%) and lower levels (TPS 1%-49%) of PD-L1 expression, respectively. Median progression-free survival (PFS) in the treated population was 9.3 months, and 12-month and 18-month PFS rates were 45% each. Median PFS was not reached in patients with PD-L1 TPS greater than or equal to 50% and was 4.2 months in patients with PD-L1 TPS 1% to 49%. Median overall survival was not reached in the treated population, and 12-month and 18-month overall survival rates were 73% and 64%, respectively. Biomarker data suggested a positive association among clinical response, three T-cell signatures, CD274 gene expression, and PD-L1 immunohistochemistry. Conclusions: First-line therapy with ramucirumab plus pembrolizumab has a manageable safety profile in patients with NSCLC, and the efficacy signal seems to be strongest in tumors with high PD-L1 expression.

Various Uses of PD1/PD-L1 Inhibitor in Oncology: Opportunities and Challenges

“…However, it has also been shown that high doses of VEFG inhibitors in combination with PD-1/PD-L1 inhibitors can directly disrupt tumor vasculature, which can lead to more severe hypoxia and thus exacerbate tumor progression ( 148 ). A study of untreated patients with advanced NSCLC treated with an anti-VEGFR monoclonal antibody in combination with Pembrolizumab showed an incidence of grade 3+ treatment-related adverse events of 42.3%, with hypertension (15.4%) and acute myocardial infarction (7.7%) being the two most common adverse reactions ( 149 ). Results from another study comparing the Atezolizumab group with the Atezolizumab combined with Bevacizumab group showed that the incidence of grade 3+ TRAEs was 5% and 20% in the two groups, respectively.…”

Cediranib Induces Apoptosis, G1 Phase Cell Cycle Arrest, and Autophagy in Non‐Small‐Cell Lung Cancer Cell A549 In Vitro

“…Drug resistance 7 BioMed Research International remains the obstacle to lung cancer treatment. Therapies targeting VEGFR signaling, such as Apatinib, Ramucirumab, and Axitinib, show promising effects on suppressing the proliferation and angiogenesis of gastric cancer, osteosarcoma, head and neck cancer, and NSCLC [27][28][29][30]. CED is a VEGFR tyrosine kinase inhibitor and shows anticancer potential against various types of tumours [31].…”

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

“…Notably, ORR was 42.3% in the whole cohort, and patients with PD-L1 ≥50% achieved an ORR= 56.3%, compared to 22.2% achieved by the other patients. Similarly, median PFS was not reached for high PD-L1 expressors, while it was 4.9 months for patients with PD-L1 = 1-49% (171).…”