Joel Neal, MD, PhD, associate professor of medicine (oncology), Division of Oncology, Stanford Cancer Institute, Stanford University, discusses the FDA accelerated approval of mobocertinib (Exkivity) in 

 exon 20 insertion–positive non–small cell lung cancer (NSCLC). 

FDA granted an accelerated approval to mobocertinib

 for the treatment of patients with locally advanced or metastatic NSCLC with 

 exon 20 insertion mutations as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. 

The regulatory decision was based on findings from a phase 1/2 trial (NCT02716116), in which mobocertinib elicited a 28% overall response rate (ORR) per independent review committee assessment and a 35% ORR per investigator assessment, Neal says. The median duration of response was 17.5 months and 11.2 months, respectively. 

This patient population represented an area of significant unmet need because early-generation EGFR TKIs were less effective at fully inhibiting 

 exon 20 insertion mutations. Therefore, mobocertinib is a welcome addition to the armamentarium, Neal concludes. 

Videos

Joel Neal, MD, PhD, discusses the FDA accelerated approval of mobocertinib in EGFR exon 20 insertion–positive non–small cell lung cancer.



Dr. Neal on the FDA Approval of Mobocertinib in EGFR Exon 20 Insertion+ NSCLC

Joel Neal, MD, PhD, assistant professor of Medicine (Oncology), Stanford University Medical Center, discusses ongoing trials in immunotherapy for patients with lung cancer.

EGFR inhibitors looking to overcome acquired resistance is a trial that Neal says he is excited to see the results of. At Stanford, there are always patients with 

-mutant lung cancer who are looking for new lines of therapy after they have failed on other treatments.

Beyond PD-1/PD-L1 immunotherapy, researchers are looking towards T-cell transgenic therapy trials. Stanford is opening new cellular therapy trials looking to reopen patient’s own T cells to try and combat the cancer in a way that they might not have otherwise.

Dr. Neal on Ongoing Trials of Immunotherapy for Lung Cancer

Joel Neal, MD, PhD, assistant professor of Medicine (Oncology), Stanford University Medical Center, discusses what immunotherapy combinations oncologists are currently using in the treatment of patients with lung cancer.

Immunotherapy can be combined with nearly any other agent, says Neal, including chemotherapy, radiation, and most importantly, other immunotherapies. The real goal is to learn how to tailor these therapies for more patients and to yield longer and more durable responses. While patient selection is improving, researchers still need to actively explore who is not appropriate to receive these therapies. Additional questions revolve around who should receive immunotherapy in first-line, as well as in second- and third-line settings.

There are a number of clinical trials in this realm. Researchers are exploring combinations with both radiation and with chemotherapy. However, Neal is not necessarily convinced that combinations with immunotherapy and chemotherapy are actually synergistic.

One novel combination being explored is ipilimumab (Yervoy) plus nivolumab (Opdivo). Preliminary evidence of the CheckMate-012 trial suggests that the combination of nivolumab plus ipilimumab achieves higher response rates in advanced non-small cell lung cancer (NSCLC) than nivolumab alone, with good tolerability.

A phase III study, CheckMate-227, is assessing nivolumab alone, nivolumab plus ipilimumab, nivolumab plus platinum-doublet chemotherapy, and platinum-doublet chemotherapy alone in patients with stage IV NSCLC. The goal of this trial is to see if any of these regimens significantly improves progression-free survival and/or overall survival.

Dr. Neal on Immunotherapy Combinations in Lung Cancer

Joel Neal, MD, PhD, assistant professor of Medicine (Oncology), Stanford University Medical Center, discusses how PD-L1 testing may have played a role in the survival differences between frontline pembrolizumab and nivolumab in non—small-cell lung cancer (NSCLC).

The PD-L1 28-8 pharmDx by Immunohistochemistry (IHC) with Interpretation, the PD-L1 test used with nivolumab, captures a wider group of positive patients than the PD-L1 22C3 IHC assay, the diagnostic test used with pembrolizumab which is more selective, says Neal.

The atezolizumab test, the SP142 PD-L1 assay, appears to have the fewest positives out of all of the tests. All three of these tests are accepting a different positive group, says Neal.

The differences in testing between nivolumab and pembrolizumab may have lead to the differences in their individual frontline lung cancer trials, he says. The patients with the tumors that express the highest levels of PD-L1 are the most likely to respond in the frontline setting.

Joel Neal, MD, PhD, assistant professor of Medicine (Oncology), Stanford University Medical Center, discusses how PD-L1 testing may have played a role in the survival differences between frontline pembrolizumab and nivolumab in non–small-cell lung cancer (NSCLC).
 

Dr. Joel Neal on Impact of PD-L1 Tests on Pembrolizumab, Nivolumab Efficacy in Frontline NSCLC

Joel Neal, MD, PhD, assistant professor of Medicine (Oncology), Stanford University Medical Center, discusses exciting advancements in the field of lung cancer over the past few years. Neal shared these insights during an interview at the 2016 International Association for the Study of Lung Cancer Multidisciplinary Symposium on Thoracic Oncology.

Immunotherapy has had a significant role in propelling the field forward, Neal explains. While patient selection is improving, researchers still need to actively explore who is not appropriate to receive these therapies. Additional questions revolve around who should receive immunotherapy in first-line, as well as in second- and third-line settings.

Targeted therapies are also making an impact, Neal says. For patients with 

-targeted agent is osimertinib (Tagrisso). Testing for this resistance mutation has also become an important topic in the field. For ALK-positive patients, alectinib (Alecensa) could be a promising agent—potentially in the frontline setting, he adds.

Joel Neal, MD, PhD, assistant professor of Medicine (Oncology), Stanford University Medical Center, discusses exciting advancements in the field of lung cancer over the past few years.

Joel Neal, MD, PhD

Articles

Dr. Neal on the FDA Approval of Mobocertinib in EGFR Exon 20 Insertion+ NSCLC

Dr. Neal on Ongoing Trials of Immunotherapy for Lung Cancer

Dr. Neal on Immunotherapy Combinations in Lung Cancer

Dr. Joel Neal on Impact of PD-L1 Tests on Pembrolizumab, Nivolumab Efficacy in Frontline NSCLC

Dr. Neal on Exciting Advancements in the Field of Lung Cancer