Early Results Positive for First-Line Avelumab in NSCLC

Virginia Powers, PhD
Published: Monday, Dec 05, 2016

Dr Claire Verschraegen

Claire Verschraegen, MD

Treatment with first-line avelumab yielded promising clinical benefit and durable antitumor activity in patients with advanced non–small cell lung cancer (NSCLC), according to a presentation at the IASLC 17th World Conference on Lung Cancer.1

After a median follow-up of 13 weeks, the objective response rate with the anti-PD-L1 immunotherapy agent was 22.4% (95% CI, 16.2-29.8) and the median progression-free survival (PFS) was 17.6 weeks (95% CI, 11.6-23.6) among 156 patients who participated in one of the NSCLC cohorts of the wide-ranging JAVELIN Solid Tumor trial,2 Claire Verschraegen, MD, director, The University of Vermont Cancer Center, said in describing early analysis data at the conference in Vienna.

JAVELIN Solid Tumor is an ongoing, multicenter phase I study that is exploring avelumab in multiple solid tumor types. The agent is a fully human IgG1 monoclonal antibody that blocks the PD-1/PD-L1 interaction but leaves PD-L2 signaling intact, thereby allowing antibody-dependent cellular cytotoxicity to contribute to antitumor activity.

“This is the largest phase I trial ever conducted, with approximately 1700 patients across 16 cohorts,” Verschraegen remarked.

In the first-line NSCLC cohort, the primary objective was to evaluate the best overall response of first-line avelumab at 10 mg/kg administered intravenously over 1 hour every 2 weeks until progression, unacceptable toxicity, or study withdrawal in patients with histologically confirmed stage IV or recurrent NSCLC.

The patients were unselected for expression PD-L1 levels, did not have an activating EGFR mutation or ALK-positive tumors, and had not received previous systemic treatment for metastatic or recurrent disease.

The median patient age was 70 years (range, 41-90 years), ECOG performance score was 0 (29.5%), 1 (69.2%), or 3 (1.3%), and tumor histology was adenocarcinoma (66%) or squamous (28.8%) in most patients. The median time from diagnosis of metastatic disease was 1.5 months (range, 0.2-92.0 months).

Although patients were not selected by PD-L1 expression levels for admission into this trial, immunohistochemistry analysis revealed that just over half (56.4%) of patients were positive for PD-L1 expression using a ≥1% staining cutoff.

The best overall response by RECIST v1.1 was complete response in 2 (1.3%) patients, partial responses in 33 (21.1%) patients, and stable disease in 67 (42.9%) patients. Progressive disease was experience by 40 participants (25.6%), and 14 (9%) patients could not be evaluated.

Tumor shrinkage was observed in 64.3% of patients, and this shrinkage was 30% or greater in 28.6% of patients.

Overall, the median treatment duration was 20 weeks (range, 2 to 46 weeks), and 64 (41.0%) patients remained on avelumab treatment. The 24-week PFS rate was 37.2% (95% CI, 28.6-45.7).

Similar to other immunotherapeutic agents, the time to response was rapid; 28 of 35 responding (80%) patients demonstrated a response by the first or second assessment and as early as 12 weeks. At data cut-off, 68.6% of responding patients maintained response.

Treatment-related adverse events (TRAEs) of any grade occurred in 103 (66%) patients with avelumab; the most common adverse events occurring in ≥5% of patients were infusion-related reaction (IRR) in 28 (17.9%) patients, and fatigue, which was reported in 27 (17.3%) patients. Grade ≥3 TRAEs consisting of IRRs and fatigue occurred in 5 patients (3.2%) patients and 4 (2.6%) patients, respectively.

Potential immune-mediated any-grade TRAEs were observed in 16 (10.3%) patients; of these, just 1 (0.6%) case of adrenal insufficiency was grade 3. No grade 3 or higher pneumonitis was seen. No treatment-related deaths occurred on study, and 11 (7.1%) patients discontinued treatment due to a TRAE.

Serving as discussant for the study, Edward B. Garon MD, said that avelumab would more than likely not expand the group of patients who could benefit from PD-1/PD-L1 inhibition. “These data support the idea that avelumab could be equivalent to the current standard treatment, but not better,” said Garon, medical director of Thoracic Oncology at David Geffen School of Medicine at UCLA, Santa Monica.

The authors noted that the PD-L1 expression analysis is ongoing, as is a phase III trial of avelumab versus platinum-containing doublet chemotherapy as first-line treatment of patients with PD-L1–positive advanced NSCLC.3

Meanwhile, avelumab is advancing in other tumor types; Verschraegen noted the recently updated results from a phase II trial of avelumab in patients with Merkel cell carcinoma (MCC).4 The FDA granted avelumab a breakthrough therapy designation as a treatment for patients with metastatic MCC following progression after at least 1 prior chemotherapy regimen.

Merck KGaA, based in Darmstadt, Germany, is sponsoring the NSCLC development of avelumab along with its US biopharmaceutical division, EMD Serono.


  1. Jerusalem G, Chen FL, Spigel D, et al. JAVELIN Solid Tumor: Safety and Clinical Activity of Avelumab (Anti-PD-L1) as First-Line Treatment in Patients with Advanced NSCLC. Presented at: 17th World Lung Cancer Conference, the Annual Meeting of the International Association for the Study of Lung Cancer (IASLC); December 4-7, 2016; Vienna, Austria.
  2. NIH Clinical Trial Registry. www,ClinicalTrials.gov. Identifier: NCT01772004.
  3. NIH Clinical Trial Registry. www,ClinicalTrials.gov. Identifier: NCT02576574.
  4. Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy refractory metastatic Merkel cell carcinoma: a multicenter, single-group-, open-label, phase 2 trial. Lancet Oncol. 2016;17(10):1374-1385. http://dx.doi.org/10.1016/S1470-2045(16)30364-3.

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