On April 1, 2019 Genprex, Inc. (NASDAQ: GNPX), a clinical-stage gene therapy company developing a new approach to treating cancer based upon a novel proprietary technology platform, reported a clinical and corporate update and the filing of financial results for the year ended December 31, 2018 on Form 10-K with the United States Securities and Exchange Commission (Press release, Genprex, APR 1, 2019, View Source [SID1234534847]).

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"Over the past year, we made great progress in advancing the development of our gene therapy platform, including Oncoprex immunogene therapy for non-small cell lung cancer," said Rodney Varner, Chairman and Chief Executive Officer of Genprex. "I’m pleased with our progress and am excited to continue development of our gene therapies for cancer into 2019 and beyond. I’m confident, given all we’ve accomplished in the past year, that 2019 will be a landmark year for Genprex."

"As we continue to advance our clinical operations and manufacturing programs, Genprex is well positioned to make 2019 a pivotal year," Julien L. Pham, MD, MPH, President and Chief Operating Officer, stated. "From our successful IPO launch on NASDAQ, to completing a $10 million private placement, we are gaining momentum to reach the important milestones we set for ourselves."

Clinical Development and Corporate Update

Genprex’s accomplishments for 2018 and early 2019 include:

Completing its initial public offering and listing of common stock on NASDAQ Capital Market.
Completing a $10 million private placement.
Contracting with Accenture to provide clinical data management services to help accelerate the clinical development of Genprex’s lead drug candidate, Oncoprex.
Contracting with WIRB-Copernicus Group (WCG) to provide site selection and feasibility services, including Institutional Review Board (IRB) and Institutional Biosafety Committee (IBC) oversight for new clinical trial sites that Genprex anticipates adding to participate in its Phase I/II clinical trial evaluating the combination of Oncoprex and erlotinib (Tarceva) in non-small cell lung cancer (NSCLC).
Selecting 4Clinics as a CRO to provide clinical and regulatory support for Genprex’s clinical development program in the form of biostatistics, statistical programming and analysis, as well as medical and scientific writing for the Phase I/II clinical trial.
Entering into an agreement with the University of Texas at Austin Dell Medical School to establish executive offices at the school’s Health Discovery Building, joining the WorkSpaces @ Texas Health CoLab.
Establishing offices in Cambridge, MA, where Dr. Julien Pham, President and COO will oversee the clinical development of Genprex’s lead drug candidate, Oncoprex.
Entering into Amendment No. 2 to Clinical Trial Agreement with The University of Texas MD Anderson Cancer Center (MD Anderson) for continued conduct of Phase I/II clinical trial at MD Anderson.
Entering into a research agreement with MD Anderson for development of a therapeutic approach to treating cancer using TUSC2, the active agent in Genprex’s lead product candidate Oncoprex, in combination with immunotherapies; and for the development and the use of biomarkers to predict patient response to TUSC2 therapy.
Entering into an agreement with Aldevron, a leading contract manufacturing organization, to supply TUSC2 (Tumor Suppressor Candidate 2) plasmid DNA for use in Genprex’s clinical development program evaluating Oncoprex for the treatment of NSCLC.
Entering into agreements with additional contract manufacturing organizations to assist with manufacturing scale-up and transfer of manufacturing processes from manufacturing facilities of MD Anderson Cancer Center to commercial facilities.
Appointing Jan Stevens, RN as Vice President of Clinical Operations, Eric Chapdelaine as Senior Director of Pharmaceutical Sciences and Manufacturing, Kalyn Dabbs as Senior Manager of Communications and Marketing, and John N. Bonfiglio, Ph.D. to Board of Directors.
Launching a state-of-the-art website and overhauled corporate communications capabilities, including the introduction of a new investors email notification system.
2018 Financial Update

Genprex’s research and development expense was $971,427 for the year ended December 31, 2018, compared to $289,934 for the year ended December 31, 2017. This increase of $681,493 was due to the Company’s focus on improving clinical strategies, expanding research activities, refining existing manufacturing processes, and developing new manufacturing and logistics processes to support future research and development activities. Genprex had a cash position of $8.6 million as of December 31, 2018.

On April 1, 2019 Turning Point Therapeutics, Inc., a clinical-stage precision oncology company designing and developing novel drugs to address treatment resistance, reported its data from four studies at AACR (Free AACR Whitepaper) 2019, highlighting potent activity of its kinase inhibitors, including repotrectinib against targeted oncogene drivers and many of their resistance mutations, and TPX-0022, a novel MET/CSF1R/SRC inhibitor (Press release, Turning Point Therapeutics, APR 1, 2019, View Source [SID1234534846]).

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Two studies highlighted the higher potency of repotrectinib as compared to other proxy investigational and the currently approved ROS1 and TRK tyrosine kinase inhibitors (TKIs), Xalkori and Vitrakvi, against fusion ROS1s, wildtype TRK, and many resistance mutations, including solvent front, gatekeeper, and compound mutations.

Alexander Drilon, M.D., Clinical Director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and an investigator in the Phase 1 portion of the ongoing TRIDENT-1 study of repotrectinib, said, "As physicians adopt next-generation sequencing to identify genomic alterations in different cancers, there is an increased need for precision therapies that target specific oncogenes, such as TRK and ROS1. Repotrectinib was found to have 10-fold or higher increased potency when compared to proxy investigational and the currently approved TRK inhibitors against wildtype (WT) TRK fusions and solvent-front mutations. The findings — while early — are significant and warrant continued clinical study."

Data for TPX-0022, a novel, internally developed MET/CSF1R/SRC inhibitor approaching IND submission in 1H 2019, were presented for the first time at the conference. TPX-0022 was designed to target MET-driven tumor cells, but also modulate the tumor microenvironment by inhibition of CSF1R. This dual modulation has demonstrated significant tumor growth inhibition in preclinical models.

The data shown in two posters highlighted the ability of TPX-0022 to potently inhibit MET-driven cancer cells and the associated signaling of known cancer pathways, inhibiting tumor growth and reducing tumor associated macrophages. This dual mechanism of action showed tumor regression and growth inhibition in multiple xenograft tumor models harboring MET amplification or MET exon 14 skipping mutations.

"We are excited to share why we believe our lead asset, repotrectinib, is a potential best-in-class ROS1 and TRK targeted TKI," said Athena Countouriotis, M.D., chief executive officer. "This is based on multiple factors, including our ongoing Phase 1 TRIDENT-1 data and what we have shown at AACR (Free AACR Whitepaper) in terms of preclinical potency against fusion ROS1s and resistance mutations, as well as WT and resistance mutations within TRKA-C. We remain encouraged by the potential for repotrectinib to make a difference in the lives of patients with a range of oncogene drivers, both patients who have yet to be treated with a kinase inhibitor, as well as those who have been treated with a prior kinase inhibitor and developed treatment resistance through a specific mutation."

Turning Point Therapeutics plans to initiate a registrational Phase 2 portion of the TRIDENT-1 Study in the second half of 2019.

Dr. Countouriotis added: "While in late stage preclinical development, our MET/CSF1R/SRC kinase inhibitor, TPX-0022, has demonstrated promising preclinical activity in an important pathway for the regulation of tumor growth. We look forward to submitting our IND in the first half of 2019 and beginning our Phase 1 study in the second half of 2019."

Additional highlights from the four studies include:

Title: Repotrectinib, a next generation TRK inhibitor, overcomes TRK resistance mutations including solvent front, gatekeeper and compound mutations
Session: Sunday Mar 31, 2019, 1:00 PM – 5:00 PM
Abstract Number: 4000

Repotrectinib was shown to be more than 10-fold as potent as a LOXO-195 proxy against wildtype TRK fusions and solvent-front mutations, and more than 100-fold more potent against certain gatekeeper mutations. Repotrectinib was the only TRK inhibitor active against the compound mutation TRKA G595R/F589L (double mutation of solvent front and gatekeeper) in preclinical Ba/F3 cells. In xenograft tumor models, repotrectinib demonstrated significant tumor regression against wildtype or mutated TRK fusions. In the ongoing TRIDENT-1 clinical trial repotrectinib was active against the solvent front mutation ETV6-TRKC G623E in an entrectinib-resistant patient with a salivary gland tumor (-82%, confirmed partial response, RECIST v1.1). Tumor regression (-33%) was achieved in a larotrectinib-resistant cholangiocarcinoma patient with LMNA-TRKA G595R and F589L mutations.

Title: Repotrectinib, a new generation ROS1 inhibitor, is highly potent against fusion ROS1s and emerging resistance mutations
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 4832

Repotrectinib demonstrated higher potency as compared to other ROS1 inhibitors against multiple ROS1 fusions and mutations, especially the solvent front and gatekeeper mutations. In xenograft tumor models, repotrectinib treatment resulted in tumor regression against wildtype or solvent-front ROS1 fusion genes. Repotrectinib demonstrated a strong inhibition profile against wildtype and various mutated ROS1s across different fusion partners when compared to many other ROS1 TKIs.

Title: TPX-0022, a polypharmacology inhibitor of MET/CSF1R/SRC for treatment of cancers with abnormal HGF/MET signaling
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 3719

TPX-0022 potently inhibited cell proliferation of the MET-amplified MKN-45 (IC50 < 0.2 nM) and SNU-5 (IC50 < 0.2 nM) gastric cancer cells. TPX-0022 caused suppression of MET auto-phosphorylation at an IC50 of approximately 0.3 nM in MKN-45 cell line. TPX-0022 also potently inhibited the phosphorylation of MET downstream signaling effectors, including AKT, ERK, STAT3 and PLCγ2 in a dose-dependent manner. In the cancer cell line and patient-derived xenograft tumor models from gastric, lung and liver cancers harboring MET amplification or MET exon14 skipping mutations, TPX-0022 caused dramatic tumor regression and tumor growth inhibition. The tumor inhibitory effect was associated with drastic inhibition of MET activity.

Title: TPX-0022, a polypharmacology inhibitor of MET/CSF1R/SRC inhibits tumor growth by promoting anti-tumor immune responses
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 3749

TPX-0022 demonstrated potent CSF1R inhibitory activity and the ability to inhibit tumor growth and promote a pro-inflammatory anti-tumor microenvironment. In contrast, the potency of a proxy compound of the type II CSF1R inhibitor PLX-3397 demonstrated a strong dependency on the concentration of mouse CSF1, as the anti-proliferation IC50 shifted from <0.1 nM to 146.4 nM when CSF1 concentration changed from baseline to 1 ng/mL. Finally, in the MC38 syngeneic mouse model, TPX-0022 effectively reduced tumor associated macrophages (TAM), altered the polarity of TAMs toward a more M1 phenotype, increased cytotoxic T cells and inhibited the growth of MC38 tumors.

About Repotrectinib

Repotrectinib (TPX-0005) is a potent and orally bioavailable investigational small molecule kinase inhibitor of ROS1, TRKs and ALK. The clinical benefits of targeting ROS1, TRK, or ALK fusion kinases have been demonstrated with multiple kinase inhibitors already approved or in clinical studies. The successes of these therapies are often overshadowed by the development of acquired resistance. The acquired solvent front mutations including ROS1 G2032R, TRKA G595R and TRKC G623R, and ALK G1202R render common clinical resistance to the current ROS1, TRK, and ALK inhibitors.

Repotrectinib has demonstrated potency against wildtype and mutated ROS1, TRK and ALK kinases, especially the clinically significant solvent front mutations, gatekeeper mutations, and emerging compound mutations after multiple lines of treatment. Repotrectinib may provide a new opportunity to inhibit the abnormal signaling of ROS1, TRK or ALK in solid malignancies, and overcome multiple resistance mechanisms seen in resistant patients. Repotrectinib is currently being evaluated in a Phase 1/2, open-label, multi-center, first-in-human study of the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements called TRIDENT-1 (www.clinicaltrial.gov number NCT03093116). Interested patients and physicians can also contact the TP Therapeutics Oncology Clinical Trial Hotline at 1-858-276-0005 or email [email protected].

On April 1, 2019 Veteran McKesson leader, reported that Brian Tyler, becomes the company’s new chief executive officer , succeeding John Hammergren. Hammergren has served as the company’s top executive since 1999 (Press release, McKesson, APR 1, 2019, View Source [SID1234534845]).

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"I am incredibly humbled and grateful for the opportunity to lead this company," said Brian Tyler, chief executive officer, McKesson Corporation. "We have a seasoned and talented Board of Directors and executives. I look forward to building on the solid foundation and global platform established by John and our management team. McKesson will continue to innovate in this changing healthcare environment, always focused on providing exceptional value to our customers and patients."

Tyler is a 22-year McKesson veteran who has headed up nearly every major business within the company as well as McKesson’s corporate strategy and business development unit. Most recently, Tyler served as COO and president of McKesson. He also joins the company’s Board of Directors.

Hammergren will remain Board chair for Change Healthcare and will continue to support Change Healthcare and McKesson as an advisor.

Edward Mueller becomes independent Board chair

Edward Mueller, previously lead independent director, takes over as independent chair of the company’s Board of Directors today and will provide strong leadership continuity for the Board. He has been a member of the company’s Board since April 2008 and the lead independent director since 2013.

Mueller served as chairman and chief executive officer of Qwest Communications from August 2007 to April 2011. He has also held the position of chief executive officer of Williams-Sonoma, Inc. and Ameritech Corporation, a subsidiary of SBC Communications. Mueller previously served on the boards for The Clorox Company, CenturyLink, Inc., Williams-Sonoma, Inc. and VeriSign, Inc.

Corporate headquarters relocates to Irving, Texas

Effective today, McKesson’s Las Colinas campus in Irving, Texas—just outside of Dallas—becomes the company’s official global corporate headquarters. Opened in 2017, the Las Colinas campus is an existing employee hub with teams performing vital functions for the company in areas such as operations, information technology, finance and accounting, marketing and sales, administration and support, purchasing, and project management.

"This is an exciting change for McKesson," said Brian Tyler. "Our Las Colinas campus offers us everything we could ask for—modern workspaces where our employees can connect and collaborate in a city with such great energy and growth. We look forward to deepening our connection in the community as a leading employer and corporate citizen. I know that we’ll thrive in the Dallas area."

The Las Colinas campus achieved LEED Gold certification, a recognition of its resource efficiency, and a WELL Building Silver certification, the first building standard focused solely on human health and wellness. Elements of the building are designed to support employee productivity and wellness, empowering employees to work the way they like while fostering team collaboration amidst an array of amenities and enhanced technology capabilities.

To learn more about career opportunities with McKesson at Las Colinas or other locations, visit the Careers page on the McKesson website.

On April 1, 2019 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported updated data from the Phase 1/2 KEYNOTE-046 study in metastatic, castration-resistant prostate cancer (mCRPC) (Press release, Advaxis, APR 1, 2019, View Source [SID1234534844]). This trial is being conducted in conjunction with Merck (known as MSD outside the U.S. and Canada) and is evaluating ADXS-PSA, one of Advaxis’ Listeria monocytogenes (Lm)-based immunotherapies, alone and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy.

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Findings will be highlighted in a poster discussion entitled "Effects of ADXS-PSA with or without Pembrolizumab on Survival and Antigen Spreading in Metastatic, Castration-Resistant Prostate Cancer Patients" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Atlanta. The poster discussion will be held today from 1:00-5:00 p.m. ET and will be led by lead author Mark N. Stein M.D., FACS, Associate Professor of Medical Oncology at Columbia University Medical Center.

KEYNOTE-046 is an open-label, multicenter, dose-determining safety and tolerability Phase 1/2 trial of 50 heavily pretreated patients conducted in two parts (Part A and Part B), with a Phase 2 expansion cohort. The objective of the study is to evaluate ADXS-PSA alone (Part A) and in combination with KEYTRUDA (Part B) for primary endpoints that include safety, tolerability and dosing. Secondary endpoints include anti-tumor activity and progression-free survival, and exploratory endpoints include associations between biomarkers of immunologic response (serum PSA) with clinical outcomes.

"There is a pressing need to improve the care and treatment of patients with metastatic, castration-resistant prostate cancer," said Dr. Stein. "Data from 37 patients in the combination arm of KEYNOTE-046 are promising as a median overall survival of 21.1 months was observed. These results compare favorably to standard-of-care therapy and to study results from similar unselected patient populations with bone-predominant disease, which indicates that this combination warrants further investigation."

Key findings from the combination arm of KEYNOTE-046 include the following:

The majority of treatment-related adverse events consisted of transient and reversible Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue. The combination of ADXS-PSA and pembrolizumab has been well-tolerated, to date, with no additive toxicity observed.
Median overall survival was 21.1 months at data cutoff (February 1, 2019) (95% CI, range 16.0 months to not-yet-reached) in this dataset of 37 patients.
Correlative immune analyses showed T-cell responses against PSA in 75% of subjects and antigen spreading in 85% of subjects.
Broader immune stimulation, including B-cell activation, was observed in the combination arm (n=37) than in the ADXS-PSA monotherapy arm (n=13).
"We are very excited to report the updated ADXS-PSA data today at the AACR (Free AACR Whitepaper) meeting," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "These data show the clinical potential of ADXS-PSA both alone and in combination with KEYTRUDA. It is meaningful that the combination has been well-tolerated in the study population because dose-related toxicities can present challenges for cancer patients, and an additive therapy with a favorable safety and tolerability profile may offer an attractive option for clinicians if developed further in this indication." He concluded, "Based on the prolonged survival data and strong safety profile to date, we believe that continued clinical development of ADXS-PSA in combination with KEYTRUDA is warranted and represents a potentially significant opportunity for Advaxis."

The full abstract is available at www.advaxis.com and the poster will be available on the Company’s website today at 1:00 p.m. ET.

About KEYNOTE-046

KEYNOTE-046 (NCT02325557) is a Phase 1/2 open-label, multicenter, dose-determination and expansion trial that evaluates the safety, tolerability and preliminary clinical activity of ADXS-PSA as monotherapy (Part A; n=14 [13 treated]), and in combination with KEYTRUDA (Part B; n=37) in heavily pretreated patients with progressive and refractory mCRPC.

About ADXS-PSA

ADXS-PSA, one of Advaxis’ Lm-based immunotherapies, utilizes live, attenuated, bioengineered Lm as a vector to deliver PSA directly to antigen presenting cells. Development is being pursued in a clinical trial collaboration and supply agreement with Merck

On April 1, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI) and Pierre Fabre reported that they have entered into an exclusive license agreement under which Pierre Fabre will develop and commercialize NERLYNX (neratinib) within Europe and part of Africa (Press release, Puma Biotechnology, APR 1, 2019, View Source [SID1234534843]). In September 2018 the European Commission granted marketing authorization for NERLYNX (neratinib) 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 the completion of prior adjuvant trastuzumab-based therapy.

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Pierre Fabre will have exclusive commercialization rights for NERLYNX in European countries excluding Russia and Ukraine, along with countries in North Africa and francophone countries of West Africa. Pierre Fabre will also be responsible for conducting additional clinical studies and leading regulatory activities in connection with the European Medicines Agency (EMA).

Under the terms of the agreement, Puma will receive an upfront payment of $60 million, as well as additional regulatory and commercial milestone payments totaling up to $345 million. In addition, Puma will receive significant double-digit royalties on NERLYNX sales throughout the territory covered by the license agreement between Puma and Pierre Fabre.

"Puma is committed to providing access to NERLYNX to patients around the world and soon physicians and patients in Europe will have commercial availability of NERLYNX," stated Alan H. Auerbach, Chief Executive Officer and President of Puma. "Pierre Fabre has a robust commercial and medical oncology infrastructure that we hope will lead to rapid commercial access to NERLYNX."

"We are thrilled to provide this new therapy to patients with HER2-positive breast cancer throughout Europe," said Frederic Duchesne, Chief Executive Officer, Pierre Fabre Pharmaceuticals. "Pierre Fabre has developed a strong expertise and presence in breast cancer treatment and the addition of NERLYNX to our historical oncology portfolio will allow us to strengthen our commercial presence. We anticipate providing access to NERLYNX to patients throughout Europe in 2019 and 2020, starting with Germany."

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

Important EU NERLYNX (neratinib) Safety Information

All suspected adverse reactions should be reported in accordance with the national reporting system.

The adverse reactions described in this section were identified in the randomized Phase 3 clinical trial (n=2840). The most common adverse reactions of any grade were diarrhoea (93.6%), nausea (42.5%), fatigue (27.3%), vomiting (26.8%), abdominal pain (22.7%), rash (15.4%), decreased appetite (13.7%), abdominal pain upper (13.2%), stomatitis (11.2%), and muscle spasms (10.0%).

The most common Grade 3-4 adverse reactions were diarrhoea (Grade 3, 36.9% and Grade 4, 0.2%) and vomiting (Grade 3, 3.4% and Grade 4, 0.1%).

Adverse reactions reported as serious included diarrhoea (1.9%), vomiting (1.3%), dehydration (1.1%), nausea (0.5%), alanine aminotransferase increased (0.4%), aspartate aminotransferase increased (0.4%), abdominal pain (0.3%), fatigue (0.3%) and decreased appetite (0.2%).

For full European prescribing information, please refer to the NERLYNX (neratinib) Summary of Product Characteristics on the European Medicines Agency website (View Source).

Important Safety Information Regarding NERLYNX (neratinib) U.S. Indication

NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with 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 inpatients 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. When patients require gastric acid reducing agents, use an H2-receptor antagonist or antacid. Separate NERLYNX by at least 3 hours with antacids. Separate NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists.
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.