LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, presented results from the Phase II SUMMIT trial, assessing the efficacy of combined neratinib, fulvestrant, and trastuzumab in patients with hormone receptor positive, HER2-negative, HER2-mutant metastatic breast cancer, at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting held in person from June 3-7 in Chicago, IL, and online. The poster, entitled Neratinib + fulvestrant + trastuzumab (N+F+T) for hormone receptor-positive (HR+), HER2-negative, HER2-mutant metastatic breast cancer (MBC): outcomes and biomarker analysis from the SUMMIT trial, was presented at the Breast Cancer -- Metastatic Poster Session (poster #1028) by Komal L. Jhaveri, MD, FACP, Medical Oncologist at Memorial Sloan Kettering Cancer Center on June 6 at 9:00 a.m. ET.
Earlier genomic analyses from a cohort treated with a combination of neratinib and fulvestrant suggest that resistance to neratinib may occur via mutant allele amplification or secondary HER2 mutations. The addition of trastuzumab to the combination of neratinib and fulvestrant in this trial demonstrated positive durable responses in patients with HR-positive, HER2-mutant MBC who had received prior CDK4/6 inhibitors (CDK4/6i).
The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study that included a cohort evaluating the efficacy of the triplet combination of neratinib (N), plus fulvestrant (F), plus trastuzumab (T), in patients with HR-positive, HER2-negative, HER2-mutant metastatic breast cancer, as identified by local genomic sequencing, who had previously received CDK4/6 inhibitors. In order to confirm the contribution of neratinib to the combination, a small, randomized cohort comparing neratinib plus fulvestrant plus trastuzumab versus fulvestrant plus trastuzumab versus fulvestrant was also included. A range of HER2 allelic variants was represented in the cohort. Patients who received the triplet regimen were enrolled in the non-randomized cohort and received 240 mg of neratinib per day intramuscularly, 500 mg intravenous fulvestrant on days 1 and 15 of Cycle 1 and then every 4 weeks, 8mg/kg body weight trastuzumab initially and then 6mg/kg every 3 weeks. Patients in the randomized cohort received either a combination of neratinib, fulvestrant, and trastuzumab, or fulvestrant and trastuzumab, or fulvestrant alone in a 1:1:1 ratio. To counter the side effects of diarrhea, loperamide prophylaxis was mandatory for the first two treatment cycles. Patients who were randomized to the combination of fulvestrant and trastuzumab, or fulvestrant alone, could cross over to receive neratinib, fulvestrant, and trastuzumab at progression. Efficacy was assessed using objective response rate (ORR) and clinical benefit rate (CBR). Tumor tissue was retrospectively assessed by central next-generation sequencing (NGS).
The table below summarizes the efficacy of SUMMIT MBC patients who received neratinib plus fulvestrant plus trastuzumab, those who received fulvestrant plus trastuzumab, and those who received fulvestrant alone; and also those who received fulvestrant plus trastuzumab or fulvestrant and then crossed over to neratinib plus fulvestrant plus trastuzumab upon progression. Patients who received neratinib plus fulvestrant plus trastuzumab (non-randomized + randomized) had a 35.3% investigator-assessed objective response rate, 14.3-month duration of response, 41.7% clinical benefit rate, and 8.2-month median progression-free survival. Neratinib appears to be a critical component of the combination therapy, as demonstrated by lack of response in the small cohort of patients treated with fulvestrant or fulvestrant plus trastuzumab, and by response in a subset of those patients upon crossover to neratinib plus fulvestrant plus trastuzumab.
Table: Efficacy Findings from HR+ Metastatic Breast Cancer Patients
Non-randomized +
Randomized
After crossover
Randomized
After crossover
Randomized HR+
HR+
from F+T to
HR+
from F to N+F+T
Prior CDK4/6i
Prior CDK4/6i
N+F+T
Prior CDK4/6i
(N+F+T, n=51)
(F+T, n=7)
(n=4)
(F, n=7)
(n=6)
18 (35.3)
0
1 (25.0)
0
2 (33.3)
1 (2.0)
0
0
0
0
17 (33.3)
0
1 (25.0)
0
2 (33.3)
Best overall response*
25 (49.0)
0
1 (25.0)
0
2 (33.3)
14.3 (6.4NE)
No response
6.2 (NENE)
No response
6.3 (6.26.4)
24 (47.1)
0
1 (25.0)
0
5 (83.3)
8.2 (4.712.7)
3.9 (1.94.1)
8.25 (NENE)
4.1 (1.64.1)
NE
These results suggest that the combination of neratinib, fulvestrant, and trastuzumab together is promising for treating HR+ and HER2-mutated MBC with prior exposure to CDK4/6i across a range of HER2 mutations.
Dr. Jhaveri, an investigator of the trial, said, Patients with hormone receptor-positive, HER2-negative, HER2-mutant metastatic breast cancer who had received prior treatment with CDK4/6 inhibitors demonstrated encouraging clinical activity with durable responses when treated with the triplet combination of neratinib with fulvestrant and trastuzumab. These responses were observed in patients whose tumors harbored a wide spectrum of HER2 mutations, including those with co-occurring HER3 mutations, regardless of ductal or lobular histology, and with a range of HER2 protein expression.
Alan H. Auerbach, Chief Executive Officer, and President of Puma Biotechnology added, HER2 mutations can be readily and accurately identified and are clinically actionable for targeted therapy in metastatic breast cancers. We are very pleased with the updated activity seen with the combination of neratinib plus trastuzumab plus fulvestrant therapy in this heavily pretreated metastatic breast cancer patient population with HER2-mutated disease.
About Puma Biotechnology
Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licenses the global development and commercialization rights to PB272 (neratinib, oral), PB272 (neratinib, intravenous) and PB357. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX is a registered trademark of Puma Biotechnology, Inc.
Further information about Puma Biotechnology may be found at https://www.pumabiotechnology.com.
Important Safety Information Regarding NERLYNX (neratinib) U.S. Indication
NERLYNX (neratinib) tablets, for oral use
INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated:
CONTRAINDICATIONS: None
WARNINGS AND PRECAUTIONS:
ADVERSE REACTIONS:
The most common adverse reactions (reported in 5% of patients) were as follows:
To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) or FDA at 1-800-FDA-1088 or https://www.fda.gov/medwatch.
DRUG INTERACTIONS:
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Puma Biotechnology Presents Outcomes from the Metastatic Breast Cancer Cohort of the SUMMIT Trial at the ASCO 2022 Annual Meeting - Business Wire
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