Breakthrough Status in Lung Cancer, Fast Track Status in Lung Cancer, and 2019 WCLC Highlights

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Breakthrough therapy designations in lung cancer, a fast track designation in lung cancer, an approval sought in breast cancer, and highlights from the 2019 World Conference on Lung Cancer.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has granted a breakthrough therapy designation to capmatinib as a first-line treatment for patients with MET exon14 skipping—mutated non—small cell lung cancer.

The decision is based on primary findings from the phase II GEOMETRY mono-study, in which capmatinib showed a 67.9% objective response rate by independent review in treatment-naïve patients with METex14-altered NSCLC.

In pretreated patients, the ORR by independent review with capmatinib was 40.6%, and the disease control rate was 78.3%. The ORR by independent review was 67.9% for treatment-naïve patients, and the DCR was 96.4%.

Results also showed that the median duration of response was 9.72 months in pretreated patients and 11.14 months in those who received the agent upfront. The median progression-free survival was 5.42 months in the pretreated group and 9.69 months for those treated in the frontline setting.

Novartis, the developer of capmatinib, stated in a press release that the regulatory filing for the MET inhibitor with the FDA will take place in the fourth quarter of 2019.

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Also in lung cancer, the FDA has granted a breakthrough therapy designation to tepotinib as a treatment for patients with metastatic non—small cell lung cancer harboring MET exon14-skipping alternations who have progressed on prior platinum-based chemotherapy.

The designation is based on data from the ongoing phase II VISION trial, in which tepotinib demonstrated an objective response rate of 50.0% as assessed by an independent review committee, and an investigator-assessed ORR of 55.3% in patients with METex14-altered NSCLC that was identified by liquid biopsy.

For patients who were identified to have METex14 alterations via tissue biopsy, the IRC- and investigator-assessed ORRs were 45.1% and 54.9%, respectively.

Results showed that the median progression-free survival was 9.5 months by IRC in liquid biopsy—assessed tumors and was 10.8 months in standard biopsy–identified tumors. Moreover, the IRC- and investigator-assessed median duration of response was 12.4 months and 17.1 months among patients whose tumors were evaluated via liquid biopsy, respectively. In those with tissue-assessed tumors, the IRC- and investigator-assessed median DOR was 15.7 and 14.3 months, respectively.

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The FDA has accepted a supplemental biologics license application for neratinib in combination with capecitabine for the treatment of patients with HER2-positive metastatic breast cancer who have failed at least 2 prior lines of HER2-directed therapies.

The application is based on findings from the phase III NALA trial, which showed that the combination of neratinib and capecitabine led to a 24% reduction in the risk of disease progression or death versus lapatinib plus capecitabine. The hazard ratio for progression-free survival favoring neratinib was 0.76, and a landmark analysis showed that the PFS curves began to separate after 6 months with 6-month PFS rates of 47% versus 38%, 1-year rates of 29% versus 15%, and 18-month rates of 16% versus 7% for the neratinib arm versus the lapatinib arm, respectively.

Additionally, a prespecified restricted means analysis for PFS was conducted that was limited to a 24-month follow-up. Data showed a mean PFS of 8.8 months for neratinib compared with 6.6 months for lapatinib.

There was a numerical but not a statistically significant overall survival benefit with neratinib. A prespecified restricted means analysis showed a mean OS of 24.0 months for the neratinib arm compared with 22.2 months for the lapatinib arm. This analysis was restricted to a 48-month follow-up.

The FDA is scheduled to make a final decision on the application by the end of April 2020.

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The FDA has granted a fast track designation to the investigational KRAS inhibitor AMG 510 for the treatment of patients with KRAS G12C—mutated non–small cell lung cancer who received prior therapy.

The decision is based on updated phase I data, which showed that AMG 150 elicited a 100% disease control rate at the target dose in evaluable patients with KRAS G12C—mutant NSCLC.

AMG 510 is a first-in-class investigational agent that selectively and irreversibly targets the KRAS G12C protein. The phase I dose-escalation/expansion study was conducted in patients with previously treated solid tumors who harbor a KRAS G12C mutation.

Additional findings from the phase I study will also be presented at the 2019 ESMO Congress.

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The World Conference on Lung Cancer took place in Barcelona this past week, highlighting the latest therapeutic advances across lung cancer settings.

First, the AXL inhibitor bemcentinib demonstrated activity in combination with pembrolizumab in patients with advanced non—small cell lung cancer who had no prior exposure to immunotherapy. Results showed that, with the combination, the objective response rate, confirmed by tissue analysis, was 40%, and the median overall survival was 12.2 months.

Secondly, the combination of durvalumab and chemotherapy showed a statistically significant improvement in patients with untreated extensive-stage small cell lung cancer, according to findings from the phase III CASPIAN trial that were presented at the meeting. The median OS increased from 10.3 months with chemotherapy alone to 13.0 months with the addition of durvalumab, which translated to a 27% reduction in the risk of death.

Additionally, data from the phase I/II LIBRETTO-001 trial showed that almost 70% of patients with pretreated RET-fusion—positive non–small cell lung cancer had objective responses to the RET inhibitor selpercatinib. The median duration of response and median progression free-survival exceeded 1.5 years. Among patients with no prior treatment, selpercatinib elicited an objective response rate of 85%.

Finally, treatment with nivolumab was associated with a 5-year overall survival rate of 13.4% versus 2.6% with docetaxel in patients with previously treated non—small cell lung cancer, according to long-term pooled efficacy and safety data from the phase III CheckMate-017 and CheckMate-057 trials.

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This week, we sat down with Dr Suresh Ramalingam, MD, of Winship Cancer Institute of Emory University, to discuss novel therapy for patients with advanced-stage non—small cell lung cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.