Neratinib Shows Interim Efficacy in EGFR+ Non–Small Cell Lung Cancer

Jonathan Goldman, MD

Treatment with the tyrosine kinase inhibitor (TKI) neratinib (Nerlynx) achieved a high percentage of responses in patients with metastatic non–small cell lung cancer (NSCLC) patients with EGFR exon 18 mutations who were dosed in a cohort during the interim analysis of the phase 2 SUMMIT basket trial (NCT01953926), Puma Biotechnology announced in a press release.

“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,” said Jonathan Goldman, MD, associate professor of Hematology & Oncology, associate director of Drug Development, and director of Clinical Trials in Thoracic Oncology at UCLA, in a statement to the press.

The EGFR-mutant NSCLC cohort in the ongoing SUMMIT study is compiled of 11 patients who had received a median of 2 prior lines of therapy in the metastatic setting prior to starting treatment in the study. Of those patients, 10 received previous treatment with an EGFR TKI such as gefitinib (Iressa), erlotinib (Tarceva), osimertinib (Tagrisso), and/or afatinib (Gilotrif).

At a 240 mg dose level, neratinib led to complete responses (CRs) in 4 out the 20 evaluable patients (40%) and partial responses (PRs) in 6 (60%) of patients. The clinical benefit rate (CBR) observed in this analysis was 80%.

The median duration of response (DOR) with neratinib treatment was 7.5 months. In addition, neratinib showed a good progression-free survival (PFS) with a median PFS of 9.1 months.

Overall, these efficacy findings met the criteria for first stage and the second stage stage of the Simon’s 2-stage design, and the study will now enroll additional patients. The target enrollment for the study is 650 patients.

Neratinib also appeared safe in patients with metastatic EGFR-mutant NSCLC, according to the interim safety analysis. In all 11 patients, there was no grade 3 or 4 diarrhea reported. However, grade 1 diarrhea occurred in 36% of patients and grade 2 diarrhea was observed in 9%. Dose holds, reductions, and discontinuation did not occur in this study as a result of diarrhea. Additionally, no patients in the study were hospitalized.

As the study continues, patients are eligible to enroll into the EGFR-mutant NSCLC cohort if they have a histologically confirmed disease for which no curative therapy exists, documented EGFR exon 18 mutation, and measurable disease per RECIST v1.1 criteria. The ineligibility criteria mention exclusion of patients who are receiving any other anticancer agents, have symptomatic or unstable brain metastases, and those who are pregnant or breast feeding.

The primary end point for this EGFR-positive metastatic NSCLC cohort is objective response rate (ORR) defined by CR and PRs per RECIST v1.1. The secondary end points include PFS, confirmed ORR, CBR, DOR, overall survival, and the incidence of adverse events.

Other cohorts included in the SUMMIT trial are of patients with HER2-positive bladder and urinary tract cancers who received neratinib in combination with paclitaxel, patients with HER-positive lung cancer who received neratinib in combination with trastuzumab (Herceptin), individuals with HER2-positive breast cancer who are given neratinib plus fulvestrant and trastuzmab, as well as patient with HER2-positive, hormone-receptor=positive breast cancer who are naive to CDK4/6 inhibition and received neratinib combined with fulvestrant and trastuzumab.

“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 TKis. 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,” said Alan H. Auerbach, chief executive officer and president of Puma Biotechnology, in a statement.

_Reference:

_{Puma Biotechnology announces interim results from the phase II SUMMIT trial of neratinib for EGFR exon 18 mutated, metastatic non-small cell lung cancer. News release. November 6, 2020. Accessed November 6, 2020. https://bit.ly/3mZL1oy​}