CLINICAL TRIALS PROFILE FOR NERLYNX

All Clinical Trials for Nerlynx

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00300781 ↗	Study Evaluating HKI-272 (Neratinib) In Subjects With Advanced Breast Cancer	Completed	Puma Biotechnology, Inc.	Phase 2	2006-08-04	The purpose of this study is to learn whether neratinib is safe and effective in treating women with advanced human epidermal growth factor receptor 2 (HER2) positive breast cancer.
NCT00706030 ↗	Study Evaluating Neratinib (HKI-272) In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer	Completed	Puma Biotechnology, Inc.	Phase 1/Phase 2	2008-04-29	The purpose of this study is to identify the highest tolerable dose of neratinib (HKI-272) in combination with vinorelbine and to assess the safety of the combination of the two drugs as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors. The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of HKI-272 and vinorelbine in patients with advanced solid tumors. In the second part of the study, approximately 60 additional subjects with metastatic ErbB-2-positive breast cancer, with no prior exposure to lapatinib, are planned to be added to better define the tolerability and preliminary activity of HKI-272 in combination with vinorelbine. Up to 20 additional subjects with ErbB-2-positive breast cancer with prior lapatinib exposure are also planned to be enrolled in part 2 for exploratory analyses.
NCT00878709 ↗	Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer	Completed	Puma Biotechnology, Inc.	Phase 3	2009-07-09	The purpose of this study is to investigate whether neratinib can further reduce the risk of recurrence from previously diagnosed HER-2 positive breast cancer after adjuvant treatment with trastuzumab.
NCT00958724 ↗	Study Evaluating Neratinib In Combination With Vinorelbine In Subjects With Advanced Or Metastatic Solid Tumors	Completed	Puma Biotechnology, Inc.	Phase 1	2009-07-01	The purposes of this study are to evaluate the safety and tolerability of neratinib in combination with vinorelbine at the maximum tolerated dose (MTD) determined in a previous study, or to determine a lower MTD of the two drugs, as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors in Japanese patients.
NCT01111825 ↗	Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer	Completed	Puma Biotechnology, Inc.	Phase 1/Phase 2	2010-04-01	This is an open-label, single arm, multi-center, multi-national, adaptive design, dose-escalation Phase 1/2 study to determine the maximum tolerated dose (MTD) of temsirolimus with daily neratinib, and to determine the safety and efficacy of this combination when given to patients with advanced breast carcinoma, specifically trastuzumab-refractory HER2-amplified disease or triple-negative disease.
NCT01808573 ↗	A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting	Completed	Puma Biotechnology, Inc.	Phase 3	2013-03-29	This is a randomized, multi-center, multinational, open-label, active-controlled, parallel design study of the combination of neratinib plus capecitabine versus the combination of lapatinib plus capecitabine in HER2+ MBC patients who have received two or more prior HER2 directed regimens in the metastatic setting.
NCT01827267 ↗	Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer	Completed	Puma Biotechnology, Inc.	Phase 2	2013-07-01	This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented somatic HER2 mutations.

Clinical Trial Conditions for Nerlynx

Condition Name

Condition Name for Nerlynx
Intervention	Trials
Breast Cancer	6
HER2-positive Breast Cancer	3
Advanced Malignant Solid Tumors	2
PR-Positive Breast Cancer	2

Condition MeSH

Condition MeSH for Nerlynx
Intervention	Trials
Breast Neoplasms	13
Neoplasms	6
Diarrhea	3
Carcinoma, Non-Small-Cell Lung	1

Clinical Trial Locations for Nerlynx

Trials by Country

Trials by Country for Nerlynx
Location	Trials
United States	178
Canada	17
Spain	14
United Kingdom	14
Australia	13

Trials by US State

Trials by US State for Nerlynx
Location	Trials
California	9
Pennsylvania	8
Massachusetts	8
New York	7
Ohio	7

Clinical Trial Progress for Nerlynx

Clinical Trial Phase

Clinical Trial Phase for Nerlynx
Clinical Trial Phase	Trials
Phase 3	3
Phase 2	15
Phase 1/Phase 2	3

Clinical Trial Status

Clinical Trial Status for Nerlynx
Clinical Trial Phase	Trials
Completed	8
Recruiting	7
Not yet recruiting	6

Clinical Trial Sponsors for Nerlynx

Sponsor Name

Sponsor Name for Nerlynx
Sponsor	Trials
Puma Biotechnology, Inc.	19
National Cancer Institute (NCI)	2
Dana-Farber Cancer Institute	2

Sponsor Type

Sponsor Type for Nerlynx
Sponsor	Trials
Industry	27
Other	19
NIH	2

Nerlynx: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction to Nerlynx

Nerlynx, marketed by Puma Biotechnology, is a tyrosine kinase inhibitor specifically designed to target the human epidermal growth factor receptor 2 (HER2), a protein that promotes the growth of cancer cells in HER2-positive breast cancer. Here, we will delve into the clinical trials, market analysis, and projections for this significant drug.

Clinical Trials Overview

Early-Stage HER2+ Breast Cancer

Nerlynx was extensively studied in the ExteNET trial, a phase 3 clinical study involving 2,840 patients with early-stage HER2-positive breast cancer. This trial compared Nerlynx to a placebo in patients who had completed trastuzumab-based adjuvant therapy. The primary endpoint was invasive disease-free survival (iDFS) at 24 months.

• Key Findings: Nerlynx reduced the risk of recurrence by 34% at 2 years compared to the placebo. At 5 years, this reduction increased to 42% in hormone receptor-positive (HR+) patients[1][5].

Metastatic HER2+ Breast Cancer

In the NALA trial, Nerlynx was evaluated in combination with capecitabine for patients with advanced or metastatic HER2-positive breast cancer who had received two or more prior anti-HER2 therapies. This phase 3 trial included 621 patients.

• Key Findings: Nerlynx plus capecitabine reduced the risk of progression by 24% compared to lapatinib plus capecitabine. The median progression-free survival (PFS) was 5.6 months for the Nerlynx group versus 5.5 months for the lapatinib group[4].

Efficacy and Safety

Extended Adjuvant Treatment

In the ExteNET trial, Nerlynx demonstrated a significant reduction in the risk of disease recurrence or death. At 2 years, 94.2% of patients on Nerlynx did not experience cancer recurrence, compared to 91.9% on the placebo. By 5 years, this benefit was sustained, with 90.8% of HR+ patients on Nerlynx remaining recurrence-free versus 85.7% on the placebo[1][5].

Metastatic Setting

The NALA trial showed that Nerlynx plus capecitabine improved PFS and overall response rate (ORR) compared to lapatinib plus capecitabine. The ORR was 32.8% for the Nerlynx group versus 26.7% for the lapatinib group. Median response duration was 8.5 months for Nerlynx versus 5.6 months for lapatinib[4].

Adverse Reactions and Tolerability

Common Adverse Reactions

The most common adverse reactions associated with Nerlynx include diarrhea, nausea, vomiting, decreased appetite, and fatigue. In the ExteNET trial, severe diarrhea was reported in 40% of patients, leading to the development of strategies to improve tolerability, such as loperamide prophylaxis and dose escalation[1][3].

Tolerability Improvement

The CONTROL Phase II study demonstrated that gradual dose escalation of Nerlynx with loperamide prophylaxis significantly reduced the rates of discontinuation due to diarrhea by 80% compared to the ExteNET trial. This approach has been validated by the FDA, enhancing the overall tolerability of Nerlynx[3].

Market Analysis and Projections

FDA Approval and Labeling

Nerlynx was approved by the FDA in 2017 for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer. The approval was broader than expected, not restricted to hormone-receptor positive patients, despite the greatest benefit seen in this subgroup. In 2020, Nerlynx was also approved in combination with capecitabine for metastatic HER2-positive breast cancer[2][4].

Pricing and Revenue Projections

Analysts predicted that Nerlynx would be priced at approximately $10,500 per month, or $126,000 per year, which is higher than initially expected. This pricing is expected to drive significant revenue, with projections suggesting that Nerlynx could surpass $2 billion in worldwide sales by 2023[2].

Market Impact and Acquisition Speculation

The broad FDA label and higher-than-expected pricing have led analysts to predict strong demand for Nerlynx. This has resulted in a significant increase in Puma Biotechnology's stock price, with some analysts suggesting that the company could be acquired due to Nerlynx's commercial potential[2].

Key Takeaways

• Clinical Efficacy: Nerlynx has demonstrated significant reductions in the risk of recurrence in early-stage HER2-positive breast cancer and improved progression-free survival in metastatic settings.
• Safety and Tolerability: Common adverse reactions include diarrhea, nausea, and fatigue, but strategies like dose escalation and loperamide prophylaxis have improved tolerability.
• Market Analysis: Nerlynx is priced at $10,500 per month, with revenue projections exceeding $2 billion by 2023.
• Projections: Strong demand and a broad FDA label position Nerlynx as a potential blockbuster, with speculation about a possible acquisition of Puma Biotechnology.

FAQs

What is Nerlynx used for?

Nerlynx is used for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer and in combination with capecitabine for advanced or metastatic HER2-positive breast cancer.

What were the key findings of the ExteNET trial?

The ExteNET trial showed that Nerlynx reduced the risk of recurrence by 34% at 2 years and by 42% at 5 years in HR+ patients compared to a placebo.

How does Nerlynx improve tolerability?

Nerlynx tolerability has been improved through strategies such as gradual dose escalation and loperamide prophylaxis, reducing the rates of discontinuation due to diarrhea.

What is the pricing of Nerlynx?

Nerlynx is priced at approximately $10,500 per month, or $126,000 per year.

What are the revenue projections for Nerlynx?

Analysts predict that Nerlynx could surpass $2 billion in worldwide sales by 2023.

Sources

1. Nerlynx.com: How Could NERLYNX® (neratinib) Fit Into My Treatment Plan?
2. FiercePharma: Puma to price new cancer med Nerlynx at a higher-than-expected ...
3. Puma Biotechnology: THE FACES OF BREAST CANCER
4. FDA.gov: FDA approves neratinib for metastatic HER2-positive breast cancer
5. Health Canada: Summary Basis of Decision for Nerlynx

Last updated: 2024-12-31