MPDL3280A in Advanced NSCLC

European Cancer Congress

For the first time, a therapy – the antibody MPDL­3280A (Genentech) – for non–small cell lung cancer (NSCLC) has achieved responses in both smokers and nonsmokers, including responses in tumors with squamous and adenocarcinoma histology.

These results of a phase 1 study in patients with metastatic NSCLC were so encouraging that experts suggested bypassing phase 2 studies and going on to phase 3
directly.

Genentech’s development program for the monoclonal antibody includes ongoing recruitment for phase 2 and 3 trials in NSCLC.

“We are at the beginning of a new era. After 30 years of research in immunotherapy for lung cancer, we have one that works, and it works in smokers,” said lead author Jean-Charles Soria, MD, PhD, Institut Gustave Roussy, Paris, France. “In this study, smokers responded much better than nonsmokers. This is great news for lung cancer patients, the majority of whom are current or former smokers. The data are preliminary, but the trends are extremely promising,” Soria added.

The study results were based on a cohort of 85 patients (53 evaluable for efficacy). Patients were treated with an IV infusion of MPDL3280A every 3 weeks for a median duration of 106 days (range, 1-450 days).
Of the 85 NSCLC patients, 55% were heavily pretreated with at least 3 prior therapies, and the majority were smokers or ex-smokers (81%); 19% were never smokers.

MPDL3280A was considered safe. The majority of adverse events were mild. No dose-limiting toxicities were identified in this trial, nor were any grades 3 to 5 adverse events reported.
Objective response rate (ORR) was 21% in the overall population (all tumor types, N=175) and 23% in NSCLC patients; 17% of responders were stable over 24 weeks.

The 24-week progression-free survival rate was 44% in squamous cell NSCLC and 46% in nonsquamous cell NSCLC.

PD-L1 expression (the target of MPDL3280A) was directly correlated with response, with the best response seen in those with the highest expression of PD-L1 on immunohistochemistry (IHC) 3. Those with IHC 3 also had less progressive disease. Although based on a very small number of patients, ORR was 46% in patients with PD-L1 IHC 2 and IHC 3, and 83% in those with IHC 3.

Responses were sustained over time in all patients except 1, Soria said.

Smoking status was a predictor of response; former/current smokers had an ORR of 26% (n=43) compared with 10% in never smokers (n=10).

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