Avelumab Shows Promise as Frontline Immunotherapy Alternative in NSCLC

Claire Verschraegen, MD

Immunotherapy is quickly becoming a mainstay in the frontline setting for the treatment of patients with metastatic non—small cell lung cancer (NSCLC).

In October 2016, the FDA approved the PD-1 inhibitor pembrolizumab (Keytruda) as a first-line treatment for patients with metastatic NSCLC whose tumors have at least 50% PD-L1 expression and who do not harbor EGFR or ALK mutations.

The FDA recently granted a priority review to a supplemental biologics license application for pembrolizumab in combination with pemetrexed plus carboplatin as a first-line treatment for patients with metastatic or advanced NSCLC, regardless of PD-L1 expression and without EGFR or ALK mutations.

Beyond pembrolizumab, the PD-L1 inhibitor avelumab showed early promise in frontline NSCLC in results presented late last year at the 2016 World Conference on Lung Cancer (WCLC). Among 156 patients with advanced NSCLC who participated in one of the lung cancer cohorts of the phase I JAVELIN Solid Tumor trial, avelumab had an objective response rate of 22.4% (95% CI, 16.2-29.8) and a median progression-free survival of 17.6 weeks (95% CI, 11.6-23.6).

Study author Claire Verschraegen, MD, who presented the findings at the WCLC, believes that with further research, avelumab could be used as an alternative immunotherapy option in lung cancer, either as a single-agent or in combination with other agents.

OncLive: Could you provide an overview of the study?

In an interview with OncLive at the WCLC, Verschraegen, a professor of Medical Oncology at the University of Vermont Cancer Center, discussed the design and findings of this early trial of avelumab and the future potential for the PD-L1 inhibitor in lung cancer.Verschraegen: This was a cohort in a phase I study of over 1500 patients. The cohort that I presented was the cohort of 156 patients with advanced lung cancer, metastatic or recurrent, that had not been treated with anything else and received avelumab as a single agent every 2 weeks, 10mg/kg dosing, for as long as they responded to the treatment. The response rate we observed was 22.4%.

Is there any potential for combining avelumab with other immunotherapy agents in the future?

Are there any remaining challenges associated with this therapy that you’d like to see addressed in trials moving forward?

What would you like the oncology community to ultimately take away from these findings?

Are there any other trials looking at avelumab?

There were very few side effects, in fact, less than what I expected with other immunotherapy agents. We had a progression-free survival of 17.3 weeks and at 24 weeks, the progression-free survival was 37% of patients, so we definitely did see a signal of activity with a very good tolerability. A phase III trial is ongoing currently to compare avelumab to chemotherapy.Absolutely. Avelumab is a bit different than pembrolizumab (Keytruda) or nivolumab (Opdivo) because it is a PD-L1 monoclonal antibody and it's different from atezolizumab (Tecentriq) because it preserves the ADCC, or, antibody-dependent cell-mediated cytotoxicity function, so we are expecting that if we are able to really cover the PD-L1 and give enough drug to the patient, we’ll also be able to also stimulate some other immune pathways and we’re hoping the immune effect will be higher in patients. Currently we see it is about equivalent, but it’s a very early cohort with unselected patients, so it’s very difficult to compare to the current blockbuster studies.One of the challenges is dosing, so making sure we have the right dose at the right amount for the right patients. The other challenges that we’re still investigating are biomarkers. The sponsor company has its own test to look at PD-L1, which is not the same that has been used by other companies. We’re studying to see exactly what this biomarker is telling us in the patients that we have put on this very early study and I think the results will inform the next trials in the future.That avelumab is very well tolerated, that we do see antitumor activity not only in the cohort that I presented, but in other cancers as well. I think this is another alternative in immunotherapy for patients in the future and I would encourage them to participate in a study of avelumab if they could.There are a lot of trials ongoing, some in combination with chemotherapy, for example in ovarian cancer, and there is the phase III trial for lung cancer that is currently being amended. There’s about 10 or 12 trials that are currently ongoing and the initial trial, the first phase I, was those 1500 patients that still has a lot of patients receiving treatment because they did well with the medication. There is still a lot of work to do.

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.