On June 2, 2018 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that interim results from the Phase Ib/II FB-10 clinical trial of Puma’s investigational drug PB272 (neratinib) given in combination with the antibody drug conjugate T-DM1 (Kadcyla, ado-trastuzumab emtansine) were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting that is currently taking place in Chicago (Press release, Puma Biotechnology, JUN 2, 2018, View Source [SID1234527104]). The presentation entitled, "NSABP FB-10: Phase IB Dose-Escalation Study Evaluating the Combination of Trastuzumab Emtansine (T-DM1) with Neratinib in Women with Metastatic HER2-Positive Breast Cancer" was selected for a poster presentation.

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The FB-10 study is an open-label, single arm study with a dose escalation phase and an expanded cohort phase to evaluate patients with HER2-positive metastatic breast cancer who had previously been treated with chemotherapy and the combination of trastuzumab (Herceptin) and pertuzumab (Perjeta). The primary aim of the Phase Ib portion of the study is to determine the safety and tolerability of the two-drug combination. The primary aim of the Phase II portion of the study is to demonstrate efficacy at the recommended Phase II dose of T-DM1 and neratinib. Study treatment during the Phase Ib portion consisted of the standard dose of T-DM1 at 3.6 mg/kg administered intravenously every 3 weeks and neratinib administered orally at escalating doses of 120, 160, 200 and 240 mg per day continuously. Primary diarrhea prophylaxis with high dose loperamide was administered to all patients. As of the date of the presentation, the study had enrolled 27 patients. Total study enrollment will be a maximum of 63 patients.

For the 20 patients who were evaluable for efficacy, the interim objective response (CR/PR) rate was 60%. More specifically, the efficacy results from the trial demonstrated that 3 patients had a complete response (CR); 9 patients had a partial response (PR); 2 patients had stable disease (SD); and 6 patients had progressive disease (PD). In addition, the poster presentation is available on the Puma Biotechnology website.

The interim safety results of the 27 patients with available safety assessments showed that the most frequently observed grade 3 adverse events were diarrhea, nausea, thrombocytopenia and hypertension. More specifically, grade 3 diarrhea was reported in 6 patients (22%), grade 3 nausea was reported in 3 patients (11%), grade 3 thrombocytopenia was reported in 4 patients (15%), and grade 3 hypertension was reported in 3 patients (11%). There was 1 dose limiting toxicity (DLT) at the 120 mg dose (1 of 6 patients), 3 DLTs at the 200 mg dose (3 of 8 patients) and 2 DLTs at the 240 mg dose (2 of 3 patients). There was no DLT for the 10 patients enrolled at the 160 mg dose. The Phase II portion of the trial is being conducted at the recommended Phase II dose of 160 mg of neratinib per day.

Dr. Jame Abraham, Director of the Breast Oncology Program at Taussig Cancer Institute, Professor of Medicine at Cleveland Clinic, and principal investigator of the study, said, "We are encouraged by these initial findings and we look forward to continuing to enroll patients in the Phase II portion of the trial to further evaluate the safety and efficacy of the combination of T-DM1 and neratinib in this patient population."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased to see the high interim objective response rate of the combination of T-DM1 and neratinib in this study’s patient population who were previously treated with both pertuzumab and trastuzumab. We look forward to continued enrollment in the Phase II portion of this trial."

IMPORTANT SAFETY INFORMATION

NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis 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 (≥ 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3 hours after antacid dosing.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information for additional safety information.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

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 www.NERLYNX.com or 1-855-816-5421.