On December 7, 2022 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported updated findings from the Translational Breast Cancer Research Consortium (TBCRC) Trial 022 at the ongoing 2022 San Antonio Breast Cancer Symposium in San Antonio, Texas (Press release, Puma Biotechnology, DEC 7, 2022, View Source [SID1234624919]). The poster (PD7-03), entitled "Neratinib and ado-Trastuzumab-Emtansine (T-DM1) for HER2+ Breast Cancer Brain Metastases (BCBM): Translational Breast Cancer Research Consortium (TBCRC) Trial 022," was presented by Rachel A Freedman, MD, MPH, Breast Oncology Center, Susan F. Smith Center for Women’s Cancers, Dana Farber Cancer Institute, at Spotlight Poster Session 7 on December 7 from 5:00 p.m. – 6:15 p.m. CT.
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TBCRC-022 is a prospective, multicenter, Phase II study to evaluate the effect of neratinib plus T-DM1 in patients with HER2-positive breast cancer brain metastases. This presentation outlined updates from three cohorts: 4A – patients with previously untreated BCBM; 4B – patients with BCBM progressing after prior local CNS-directed therapy without prior T-DM1 exposure; and 4C – patients with BCBM progressing after prior local CNS-directed therapy with previous T-DM1 exposure. Data from previous cohorts from this study were reported at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting. Patients with measurable HER2-positive BCBM received neratinib 160 mg orally once daily plus T-DM1 3.6 mg/kg intravenously every 21 days in the three parallel-enrolling cohorts. Diarrhea prophylaxis with colestipol and loperamide was required during cycle 1. All enrolled patients underwent a brain MRI plus CT scan of the chest/abdomen/pelvis every 6 weeks for 18 weeks, followed by every 9 weeks thereafter.
The primary endpoint, Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM), was evaluated in each cohort separately. The efficacy results from the trial showed that CNS Objective Response Rate by RANO-BM was 33.3% of patients in cohort 4A, 29.4% in cohort 4B, and 28.6% in cohort 4C. Rates of response + stable disease greater than or equal to 6 months were 50% in cohort 4A, 35.3% in cohort 4B, and 33.3% in cohort 4C.
Intracranial activity was observed for the combination of neratinib plus T-DM1 in all three cohorts, including in patients with prior T-DM1 exposure, suggesting a reversal of resistance to T-DM1. Overall, the most frequently observed adverse event was diarrhea, grade 2 (32%) and grade 3 (23%). These data provide additional evidence for the consideration of neratinib-based combinations in patients with HER2-positive BCBM.
"Neratinib given in combination with T-DM1 showed promising activity in patients with heavily pre-treated HER2-positive disease metastatic to the CNS including patients with prior T-DM1 exposure, which may suggest that neratinib is playing a role in reversing resistance to T-DM1," said Rachel A. Freedman, MD, MPH, Breast Oncology Center, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute. "Despite the introduction of several new treatments for patients with HER2-positive metastatic breast cancer, CNS progression events remain a major source of patient morbidity and mortality. The data from this study provide additional evidence for consideration of neratinib- based combinations in patients with HER2-positive breast cancer brain metastases."
Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are pleased with the results from the TBCRC-022 trial on the combination of neratinib and T-DM1. As a small molecule that can cross the blood brain barrier, neratinib potentially offers patients with HER2-positive metastatic breast cancer that has metastasized to the CNS a novel HER2 targeted treatment option. This data adds to the existing body of data that we have from the other previously presented arms from the TBCRC-022 trial that continue to demonstrate that neratinib is active in patients with HER2-positive breast cancer brain metastases."