Puma Biotechnology Presents Outcomes from the Metastatic Breast Cancer Cohort of the SUMMIT Trial at the ASCO 2022 Annual Meeting
Puma Biotechnology (NASDAQ: PBYI) presented Phase II SUMMIT trial results at ASCO, highlighting the efficacy of neratinib, fulvestrant, and trastuzumab in hormone receptor-positive, HER2-negative, HER2-mutant metastatic breast cancer. The trial showed a 35.3% objective response rate and 41.7% clinical benefit rate among patients previously treated with CDK4/6 inhibitors. The combination therapy led to a median progression-free survival of 8.2 months, indicating its potential for durable responses across various HER2 mutations.
- 35.3% objective response rate reported from the triplet therapy.
- Median progression-free survival of 8.2 months.
- 41.7% clinical benefit rate observed in treated patients.
- Potential resistance due to mutant allele amplification reported in previous studies.
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
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) |
|||||
Objective response (confirmed CR/PR)a, n (%) | 18 (35.3) |
0 |
1 (25.0) |
0 |
2 (33.3) |
||||
CR | 1 (2.0) |
0 |
0 |
0 |
0 |
||||
PR | 17 (33.3) |
0 |
1 (25.0) |
0 |
2 (33.3) |
||||
|
|
|
|
|
|||||
Best overall response* |
|
|
|
|
|||||
(confirmed or unconfirmed PR or CR), n (%) | 25 (49.0) |
0 |
1 (25.0) |
0 |
2 (33.3) |
||||
|
|
|
|
|
|||||
Median DORb, months ( |
14.3 (6.4–NE) |
No response |
6.2 (NE–NE) |
No response |
6.3 (6.2–6.4) |
||||
|
|
|
|
|
|||||
Clinical benefitc, n (%) | 24 (47.1) |
0 |
1 (25.0) |
0 |
5 (83.3) |
||||
|
|
|
|
|
|||||
Median PFS, months ( |
8.2 (4.7–12.7) |
3.9 (1.9–4.1) |
8.25 (NE–NE) |
4.1 (1.6–4.1) |
NE |
||||
Data cut-off: |
||||||||
CR, confirmed response; PR, partial response; CI, confidence interval; DOR, duration of response; NA, not applicable; NE, not estimable; PFS, progression-free survival | ||||||||
a Objective response defined as either a complete or partial response that is confirmed no less than 4-weeks after the criteria for response are initially met; | ||||||||
b Kaplan-Meier analysis. For crossover patients, calculated from time of crossover to N+F+T. | ||||||||
c Clinical benefit is defined as confirmed CR or PR or stable disease (SD) for ≥24 weeks (within +/– 7-day visit window) |
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.
About
Further information about
Important Safety Information Regarding NERLYNX® (neratinib)
NERLYNX® (neratinib) tablets, for oral use
INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated:
- As a single agent, for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy.
- 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.
CONTRAINDICATIONS: None
WARNINGS AND PRECAUTIONS:
- Diarrhea: Manage diarrhea through either NERLYNX dose escalation or loperamide prophylaxis. If diarrhea occurs despite recommended prophylaxis, treat with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
- Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.
- Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS:
The most common adverse reactions (reported in ≥
- NERLYNX as a single agent: Diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection.
- NERLYNX in combination with capecitabine: Diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight decreased, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms.
To report SUSPECTED ADVERSE REACTIONS, contact
DRUG INTERACTIONS:
- Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. Separate NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists. Or separate NERLYNX by at least 3 hours with antacids.
- Strong CYP3A4 inhibitors: Avoid concomitant use.
- P-gp and moderate CYP3A4 dual inhibitors: Avoid concomitant use.
- Strong or moderate CYP3A4 inducers: Avoid concomitant use.
- Certain P-gp substrates: Monitor for adverse reactions of P-gp substrates for which minimal concentration change may lead to serious adverse reactions when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:
- Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information for additional safety information.
To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at https://www.NERLYNX.com or 1-855-816-5421.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220606005244/en/
info@pumabiotechnology.com
ir@pumabiotechnology.com
david.schull@russopartnersllc.com
Source:
FAQ
What were the key findings of Puma Biotechnology's SUMMIT trial presented at ASCO 2022?
What is the clinical benefit rate reported in the SUMMIT trial for PBYI?
What was the median progression-free survival in the SUMMIT trial for treating metastatic breast cancer?