LOS ANGELES—Puma Biotechnology Inc. has announced interim results from the ongoing SUMMIT trial of neratinib in the cohort of metastatic non-small cell lung cancer (NSCLC) patients with epidermal growth factor (EGFR) exon 18 mutations that have been previously treated with an EGFR-targeted tyrosine kinase inhibitor (TKI).
The Phase 2 SUMMIT basket trial is an open-label, multicenter, multinational study to evaluate the safety and efficacy of neratinib in patients who have solid tumors with activating EGFR exon 18 or HER2 mutations. In the EGFR exon 18 mutation cohort, patients with lung cancer with single or complex EGFR exon 18 mutations — who were EGFR TKI naive, or were previously exposed to EGFR TKI — were enrolled into this study and received 240 mg of neratinib daily.
This 11 patient cohort had received a median of two prior lines of therapy in the metastatic setting (range 1-3 prior regimens) before entering the trial. Ten patients had been previously treated with an EGFR targeted tyrosine kinase inhibitor (gefitinib, erlotinib, osimertinib and/or afatinib).
“These early study results are very exciting and may prove to be an effective option for NSCLC patients with EGFR exon 18 mutations for whom very few effective treatments exist once they fail first-line FDA approved TKI therapy,” stated Jonathan Goldman, M.D., who is associate professor of Hematology & Oncology, associate director of Drug Development and director of Clinical Trials in Thoracic Oncology at the University of California, Los Angeles.
The interim efficacy results showed that for the ten evaluable patients treated with a prior EGFR tyrosine kinase inhibitor, six (60 percent) experienced a partial response, which included four patients (40 percent) with a confirmed partial response. Eight patients (80 percent) experienced clinical benefit (defined as confirmed complete response or partial response, or stable disease for at least 16 weeks).
The median duration of response was 7.5 months, with median progression free survival of 9.1 months. The success criteria for both stages of the Simon’s two-stage design were met, and enrollment continues in the second stage.
The safety profile observed in the subgroup of patients with EGFR exon 18 mutated NSCLC showed that for the 11 patients who received neratinib in the trial, there were no reports of grade 3 or higher diarrhea. Four patients (36 percent) reported grade 1, and one patient (9 percent) reported grade 2. No patients required a dose hold, dose reduction, hospitalization or discontinuation of neratinib due to diarrhea.
“We are very pleased with the preliminary activity seen with neratinib in this cohort of patients with EGFR exon 18 mutated NSCLC who have previously been treated with EGFR targeted tyrosine kinase inhibitors,” added Alan H. Auerbach, president and chief executive officer of Puma Biotechnology. “We believe that there is a need for new treatments for these patients and we look forward to the further development of neratinib in this patient population.”