On December 6, 2018 Molecular Partners AG (SIX: MOLN), a clinical-stage biopharmaceutical company pioneering the use of DARPin therapeutics* to treat serious diseases, reported the continued progress of its pipeline of proprietary therapeutic product candidates in oncology and immuno-oncology, as well as in ophthalmology together with its partner Allergan (Press release, Molecular Partners, DEC 6, 2018, View Source [SID1234531925]).

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On its R&D Day in New York, entitled "Building Tomorrow’s Breakthroughs," the company elaborates on its refined development plans for its most advanced proprietary candidate MP0250 in multiple myeloma (MM). In particular, the company announces its intention to initiate a second phase 2 trial for MP0250 in MM. This complementary trial will recruit patients with relapsed or refractory MM who have failed at least two lines of therapy including a proteasome inhibitor and an immunomodulatory drug (IMiD) and in whom the most recent therapy was IMiD-based. Patients will be treated with MP0250 in combination with Pomalidomide and dexamethasone. The design of the initial phase 2 trial for MP0250 in MM will be updated to recruit patients with a proteasome inhibitor (PI) based regimen as the most recent therapy. Those patients continue to be dosed with MP0250 in combination with Velcade and dexamethasone.

Molecular Partners also presents additional preclinical data on MP0310, its most advanced multi-specific (FAP x 4-1BB) DARPin immuno-oncology compound, which is expected to move into the clinic in 2019. In addition, data on FAP x CD40, a second multi-specific preclinical DARPin therapeutic in immuno-oncology, will be presented.

"I am pleased to report on our progress in oncology and our efforts to build a sustainable pipeline of DARPin therapeutics," said Patrick Amstutz, Chief Executive Officer of Molecular Partners.

Pamela A. Trail, Chief Scientific Officer of the company, added: "Our unique DARPin designs have the potential to translate into novel therapeutics across the landscape of oncology. Going forward, we will focus on several key areas of therapeutic intervention which are in the sweet spot of our DARPin technology."

In addition to an overview of the Molecular Partners clinical and preclinical pipeline, the R&D Day will feature presentations by the following experts:

Dr. Robert Orlowski, Chairman, Ad Interim, Director of Myeloma, Professor of Medicine Departments of Lymphoma/Myeloma and Experimental Therapeutics, MD Anderson Cancer Center
Dr. Yehia Hashad, Vice President and Global Head of Clinical Development, Ophthalmology, Allergan
Logistics
The R&D Day for institutional investors, sell-side analysts, investment bankers, and business development professionals will take place at The Yale Club, 50 Vanderbilt Avenue, New York City, from 11:30 am – 2:30 pm EST. To RSVP email Susan A. Noonan at [email protected].

Attendees are invited to check at 11:30 am EST. The presentations will begin at 12:00 pm, followed by a Q&A session. Lunch will be served.

Audio webcast
A respective audio webcast will be accessible, both live and as a replay, on the investors section of the company’s website, along with the accompanying presentation slides.

Financial Calendar
November 1, 2018 – Q3 2018 Management Statement
December 6, 2018 – R&D Day in New York
February 7, 2019 – Publication of Full-year Results 2018 (unaudited)
March 15, 2019 – Expected Publication of Annual Report 2018
April 16, 2019 – Annual General Meeting
May 9, 2019 – Interim Management Statement Q1 2019
View Source

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage more than 5 targets at once, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics.
The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.

With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapeutics have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology, and is advancing a proprietary pipeline of DARPin drug candidates in oncology and immuno-oncology. The most advanced global product candidate is abicipar, a molecule currently in phase 3, in partnership with Allergan. Several DARPin molecules for various ophthalmic indications are also in development. The most advanced DARPin therapeutic candidate wholly owned by Molecular Partners, MP0250, is in phase 2 clinical development for the treatment of solid tumors and hematological tumors. MP0274, the second-most advanced DARPin drug candidate owned by Molecular Partners, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 is currently in phase 1. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG

On December 6, 2018 Stemline Therapeutics, Inc. (Nasdaq: STML), a biopharmaceutical company focused on the development and potential commercialization of novel oncology therapeutics, reported that updated data from multiple ELZONRISTM (tagraxofusp; SL-401) clinical trials at the 2018 ASH (Free ASH Whitepaper) Annual Meeting (Press release, Stemline Therapeutics, DEC 6, 2018, View Source [SID1234531924]). Presentations are now available on the Stemline website, www.stemline.com, under the Scientific Presentations tab.

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Key Outcomes from Pivotal Trial of ELZONRIS in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Across all 3 stages, 42 patients received ELZONRIS (12 ug/kg/day)
• In first-line patients with BPDCN, ELZONRIS (12 ug/kg/day)
– 90% (26/29) overall response rate (ORR)
– 72% (21/29) rate of CR + CRc (complete response + clinical CR [CR with residual skin abnormality])
– 45% (13/29) of patients were bridged to stem cell transplant (SCT)
• In relapsed/refractory patients with BPDCN, ELZONRIS (12 ug/kg/day)
– 69% (9/13) ORR
– 38% (5/13) CR + CRc + CRi rate
– 1 patient was bridged to SCT
• Median overall survival (OS) was not yet reached in first-line patients treated with ELZONRIS at 12 ug/kg/day across all stages. Median follow up time is 23.0 months (range of 0.2 – 41+ months)
• Most common treatment-related adverse events (TRAEs) in all patients treated across all trials at 12 ug/kg/day dose (N=148) were: alanine aminotransferase increase (43.9%), aspartate aminotransferase increase (43.9%), hypoalbuminemia (43.9%), and thrombocytopenia (26.4%). TRAEs included capillary leak syndrome (CLS) (16.9%) which was grade 5 in 1.5% (3/202) of patients across all trials and doses and 0.6% (1/166) of patients across all trials at 12 ug/kg/day; a myocardial infarction, grade 5, occurred in a patient (12 ug/kg/day) with grade 4 CLS, as previously reported.

Stage 3 pivotal cohort (13 first-line BPDCN patients treated with SL-401 at 12 ug/kg/day):
• Met its primary endpoint with a 54% (7/13) CR + CRc rate (95% CI: 25.1, 80.8)
• 77% (10/13) ORR
• 46% (6/13) of patients were bridged to SCT
In the U.S., the ELZONRIS biologics license application (BLA) is under Priority Review, with a February 21, 2019 PDUFA action date

In the E.U., the European Medicines Agency (EMA) has granted accelerated assessment to the planned Marketing Authorization Application (MAA), which is expected to be submitted in the first quarter of 2019
Key Outcomes from Ongoing Clinical Trial of ELZONRIS in Patients with Relapsed/Refractory Chronic Myelomonocytic Leukemia (CMML)

ELZONRIS demonstrated efficacy (spleen and bone marrow responses), with a manageable safety profile, in patients with relapsed/refractory CMML, an area of unmet medical need

100% of evaluable patients had reduction in baseline splenomegaly
– 80% had reduction by ≥50%
– 67% with baseline spleen size ≥5cm had reduction by ≥50%

3 bone marrow complete responses (BMCRs)

1 patient bridged to stem cell transplant in remission on ELZONRIS

Most common TRAEs include hypoalbuminemia (35%), thrombocytopenia (35%), nausea (30%) and vomiting (30%). Most common TRAEs, grade 3+, include thrombocytopenia (35%) and nausea (5%). CLS was reported in 15% of patients, with no cases of grade 3 or higher observed

Splenomegaly has historically been associated with serious sequelae including early satiety and intractable pain, as well as poor transplant outcomes and a higher propensity for AML transformation

Targeting the proliferative component of CMML, namely alleviation of splenomegaly, could result in meaningful clinical benefit and address a key unmet medical need
Next Steps

Patient enrollment and follow up continues, and additional updates are planned in 2019

Based on the encouraging results seen in this trial, a registrational trial design, or pivotal cohort, is being designed
Key Outcomes from Ongoing Trial of ELZONRIS in Patients with Relapsed/Refractory Myelofibrosis

ELZONRIS monotherapy demonstrated efficacy (improvements in splenomegaly), with a manageable safety profile, in patients with relapsed/refractory MF, an area of unmet medical need; Patient enrollment and follow up continues

100% of evaluable patients with monocytosis and baseline spleen size ≥5cm, had reduction in baseline splenomegaly
– 80% had reduction by ≥29%; 40% had reduction by ≥45%
– Historically, monocytosis has been associated with poor prognosis in certain MF patients

57% of evaluable patients, with baseline spleen size ≥5cm, had reduction in baseline splenomegaly
– 43% had reduction by ≥29%; 21% had reduction by ≥45%

6 patients with spleen response had treatment duration of 6+ months; 5 patients ongoing
– 5 patients with baseline thrombocytopenia (platelet count <100K) had treatment duration of 6+ months; 4 ongoing
– 3 patients with baseline monocytosis (>1×109/L) had treatment duration of 8+ months; 2 patients ongoing

Initial quality of life (QOL) assessments appear promising; full symptom score analyses are ongoing

Most common TRAEs include headache and hypoalbuminemia (each 22%), and alanine aminotransferase increased and thrombocytopenia (each 17%). The most common TRAE, grade 3+, was thrombocytopenia (8%). There was one case of CLS, which was grade 3.
Next Steps

Patient enrollment and follow up continues, and additional updates are planned in 2019

Based on these encouraging results, next steps are being evaluated including single agent, combination, and registration-directed trials in patients with relapsed/refractory MF, including in poor-prognosis MF patients with monocytosis, an area of unmet medical need
Ivan Bergstein, M.D., CEO of Stemline, commented "The ELZONRIS clinical presentations showcased at ASH (Free ASH Whitepaper) demonstrate a broad clinical potential in a wide range of malignancies. In particular, we believe that our data in relapsed/refractory CMML and MF provides important clinical proof-of-concept in two indications with unmet medical need, and underscores just two of the many potential expansion opportunities that targeting CD123 offers. At ASH (Free ASH Whitepaper), we continued to ramp-up our disease awareness campaign for BPDCN ahead of the upcoming FDA decision on the ELZONRIS BLA. Also, our sales force is prepared and poised to launch ELZONRIS, should approval be obtained. In parallel, our clinical development team is moving forward with plans to expand efforts, including initiating one or more registration-directed trials in indications beyond BPDN, while also continuing to pursue novel entry points in CD123+ acute myeloid leukemia (AML) and other malignancies."

About BPDCN
To learn more about BPDCN, please visit the disease awareness website at www.bpdcninfo.com.

On December 6, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), reported that the United States Patent and Trademark Office has issued US patent 10,144,770, entitled "Chimeric Receptors and Uses Thereof in Immune Therapy." The ‘770 patent covers design and use of the chimeric Antibody-Coupled T-cell Receptor (ACTR) platform technology that enables an engineered immune cell to be targeted via an antibody to attack certain cell types, including cancer cells (Press release, Unum Therapeutics, DEC 6, 2018, View Source [SID1234531923]). An ACTR-expressing T cell offers a number of potential advantages over alternative cell therapy approaches and clinical proof-of-concept for the ACTR technology has been demonstrated in two independent clinical trials sponsored by Unum Therapeutics. ACTR therapeutic programs targeting non-Hodgkin lymphoma, multiple myeloma, and HER2+ advanced cancers are currently in early stages of clinical testing.

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The initial ACTR construct was developed by Dr. Dario Campana, a well-renowned cancer researcher recognized as an inventor of the chimeric antigen receptor that forms the basis for tisagenlecleucel, the world’s first approved CAR-T therapy. Working initially at St. Jude Children’s Research Hospital and later at the National University of Singapore, Dr. Campana and his team were able to demonstrate in mouse studies that ACTR-expressing T cells exhibit potent anti-tumor activity. Researchers at Unum Therapeutics extended upon this work, demonstrating that a wide range of functional ACTR receptors could be constructed using different building blocks derived from various human immune cell receptors.

Under the terms of a 2014 three-way license agreement between Unum Therapeutics, the National University of Singapore, and St. Jude Children’s Research Hospital, Unum Therapeutics controls exclusive, world-wide rights to develop and commercialize ACTR therapies covered by the ‘770 patent. Unum has continued to build a broad patent portfolio encompassing further enhancements to and novel applications of the ACTR technology. In addition to the ‘770 patent covering ACTR in the United States, previously granted patents protect the technology in Europe, Japan, and other important territories. The full text of the ‘770 patent is available from the US Patent and Trademark Office website at View Source;Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=10144770.PN.&OS=PN/10144770&RS=PN/10144770.

On December 6, 2018 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that results from an ongoing Phase II clinical trial of Puma’s drug neratinib are being presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 6, 2018, View Source [SID1234531921]). The presentation entitled, "Neratinib + fulvestrant for HER2-mutant, HR-positive, metastatic breast cancer: Updated results from the phase 2 SUMMIT trial," are being presented at a Spotlight Session by Lillian M. Smyth, M.D., Breast Medicine Service and Early Drug Development Service, Memorial Sloan Kettering Cancer Center, an investigator of the trial.

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Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets. NERLYNX was granted marketing authorization by the European Commission for the extended adjuvant treatment of hormone receptor-positive HER2-positive early stage breast cancer in September 2018.

The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study to evaluate the safety and efficacy of neratinib administered daily to patients who have solid tumors with activating HER2 or HER3 mutations. In the HER2-mutant, HR-positive breast cancer cohort, 47 patients received 240 mg of neratinib daily in combination with fulvestrant at the labeled dose. In this cohort, 43 patients (92%) had HER2-non-amplified disease, and patients had received a median of 3 prior lines of therapy in the metastatic setting (range 0-11 prior regimens) before entering the trial. All patients had been previously treated with an endocrine agent prior to entering the study, including 25 patients (53%) who had received prior fulvestrant. Further, 20 patients (43%) received prior cyclin-dependent kinase 4/6 (CDK4/6)-inhibitor therapy.

The efficacy summary of the breast cohort that received neratinib + fulvestrant is shown in Table 1 below. The interim efficacy results from the trial showed that for the 47 efficacy evaluable patients, 14 patients (30%) experienced an objective response, which included 4 patients with a complete response and 10 patients with partial responses, and 22 patients (47%) experienced clinical benefit (clinical benefit is defined as confirmed complete response or partial response or stable disease for at least 24 weeks). The median duration of response was 9.2 months and the median progression free survival was 5.4 months. Subgroup analysis demonstrated that patients who had received prior fulvestrant or CDK4/6 inhibitor targeted therapy prior to entering the trial also benefited from treatment of neratinib + fulvestrant. Of note, 6 patients (30%) with prior CDK4/6-inhibitor exposure demonstrated confirmed responses, with the duration of responses ranging from 4.5–14.8 months. Four patients were still on treatment at the time of data reporting.

Table 1: HER2-Mutant, HR-Positive Metastatic Breast Cancer
Phase II SUMMIT Trial Efficacy Summary

Neratinib + Fulvestrant
Subgroups
All Patients
(n=47)

Prior Fulvestrant
(n=25)

Prior CDK4/6 Inhibitor-Based
Therapy (n=20)

Efficacy Endpoint a :
Objective response (confirmed)b – n 14 4 6
CR 4 0 1
PR 10 4 5
Objective response rate (95% CI) 30 (17–45) 16 (5–36) 30 (12–54)
Medianc DOR, months (95% CI) 9.2 (5.5–16.6)
DOR for each responder 9.2; 9.3*; 14.8*; 16.6 4.5; 7.3; 9.2*; 9.3*; 11.2*; 14.8*

Clinical benefitd – n 22 9 8
CR or PR 14 4 6
SD 8 5 2
Clinical benefit rate (95% CI) 47 (32–62) 36 (18–58) 40 (19–64)

Medianc PFS (95% CI) time to event, months 5.4 (3.7–9.2) 3.7 (3.5–6.9) 4.1 (1.9–10.9)

Patients with RECIST v1.1 Measurable Disease
Subgroups
Efficacy Endpoint a : All Patients
(n = 39)

Prior Fulvestrant
(n = 21)

Prior CDK4/6 Inhibitor-Based
Therapy (n=15)

Objective response (confirmed)b – n 12 4 5
CR 2 0 0
PR 10 4 5
Objective response rate (95% CI) 31 (17–48) 19 (5–42) 33 (12–62)

Medianc DOR, months (95% CI) 9.0 (4.5–16.6)
DOR for each responder 9.2; 9.3*; 14.8*; 16.6 4.5; 7.3; 9.2*; 9.3*; 14.8*

Clinical benefitd – n 18 8 6
CR or PR 12 4 5
SD 6 4 1
Clinical benefit rate (95% CI) 46 (30–63) 38 (18–62) 40 (16–68)
Medianc PFS (95% CI) time to event, months 5.4 (3.5–10.3) NA NA
a

Response is based on investigator tumor assessments per RECIST v1.1 or modified PERCIST for patients with only PET-evaluable lesions.

Overall objective response (ORR) is defined as either a complete or partial response that is confirmed no less than 4-weeks after the criteria for response are initially met.

Kaplan-Meier analysis

Clinical benefit rate (CBR) is defined as confirmed CR or PR or stable disease (SD) for at least 24 weeks (within +/- 7 day visit window).

Patient still on treatment at time of data cut; DOR, duration of response; PFS, progression free survival; NA, not available

The safety profile observed in neratinib + fulvestrant-treated breast cancer patients in the SUMMIT study was consistent with that observed previously in metastatic patients with HER2 amplified tumors. With anti-diarrheal prophylaxis and management, diarrhea was not a treatment-limiting side effect in SUMMIT. The interim safety results of the study showed that the most frequently observed adverse event was diarrhea. For the 47 patients enrolled in the trial, 11 patients (23%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for those patients was 1.5 days. No patients permanently discontinued neratinib due to diarrhea.

Dr. Lillian Smyth said, "Somatic HER2 mutations represent a distinct class of oncogenic driver mutations that appear to be clinically actionable for metastatic breast cancers. The combination of neratinib plus fulvestrant therapy demonstrates encouraging clinical activity with durable responses in this heavily pretreated metastatic breast cancer patient population with HER2-mutated and hormone receptor-positive disease."

Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are very pleased with the updated activity seen with neratinib in combination with fulvestrant in this cohort of patients with HER2-mutated breast cancer. We look forward to the further development of the combination of neratinib and fulvestrant in this patient population."

On December 6, 2018 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, is reported that updated results from a Phase II clinical trial of Puma’s drug neratinib at the 2018 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 6, 2018, View Source [SID1234531920]). The presentation entitled, "The impact of neratinib with or without anti-diarrheal prophylaxis on health-related quality of life in HER2-positive early stage breast cancer: Analyses from the ExteNET and CONTROL trials." is being presented by Dr. Suzette Delaloge, Institut Gustave Roussy, Paris, France, at a poster session on December 6 from 7:00 – 9:00 a.m. CST. A full copy of the poster is available on the Puma Biotechnology website at www.pumabiotechnology.com.

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Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets. NERLYNX was granted marketing authorization in September 2018 by the European Commission for 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

Diarrhea is the main side effect of neratinib. In ExteNET, where antidiarrheal prophylaxis was not mandated by the study protocol, grade 1/2 diarrhea was reported in 55% and 34% of patients in the neratinib and placebo groups, respectively, and grade 3 diarrhea occurred in 40% and 2%, respectively. Because neratinib-induced diarrhea occurs early in the course of treatment, a structured high dose regimen of loperamide prophylaxis given for one or two cycles has been introduced to better manage this side effect. The Phase II CONTROL study, conducted in the exact same setting as ExteNET, investigated the effectiveness of anti-diarrheal prophylaxis with loperamide alone or in combination with budesonide or colestipol in the prevention of neratinib-associated diarrhea.

Both ExteNET and CONTROL assessed patient-reported outcomes using the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B), a validated instrument for the assessment of health-related quality of life (HRQoL) in breast cancer. Total scores of FACT-B range from 0-144, with higher scores indicating better HRQoL. A change of 7-8 points in the FACT-B total score is considered clinically meaningful. Preliminary HRQoL findings from the CONTROL study were presented in 2017 and are posted on Puma’s website at www.pumabiotechnology.com/pr20171206.html. The poster presented at SABCS reports more detailed and mature HRQoL data from CONTROL, and compares it to the HRQoL findings from the ExteNET study.

In ExteNET, 17% of patients in the neratinib group and less than 1% of patients in the placebo group discontinued treatment because of diarrhea. In CONTROL, 20% of patients in the loperamide cohort, 11% in the budesonide plus loperamide cohort, and 4% in the colestipol plus loperamide cohort discontinued treatment due to diarrhea.

The poster presentation demonstrates that in both studies decreases in FACT-B total scores seen in early months were followed by recovery towards baseline levels. Decreases in FACT-B total scores observed did not cross a clinically meaningful threshold at any time point.

In the ExteNET study, a transient decrease in FACT-B total score was observed with neratinib at month 1 (mean change from baseline, –4.6 points) followed by recovery towards baseline. Decreases were also evident in the placebo group, with mean changes from baseline ranging from –3.5 to –1.7 points during study treatment. After month 3, mean changes from baseline were similar in neratinib and placebo arms. None of these changes reached clinically meaningful thresholds (7–8 points) at any time point.

The presentation also shows that in the CONTROL study, FACT-B total scores decreased from baseline in all cohorts; mean changes from baseline ranged from –6.0 to –1.5 points over the course of study treatment. In the cohorts that had completed follow-up (loperamide, budesonide plus loperamide), the largest decreases in FACT-B total scores were evident during months 1 and 3 followed by recovery towards baseline levels. None of these changes reached clinically meaningful thresholds (7–8 points) at any time point.

An evaluation of each of the FACT-B subscales (n=5) were evaluated and this analysis suggested that physical well-being (PWB) was the only subscale where the clinically important difference (CID) threshold was crossed in both trials. In the ExteNET study, in the neratinib arm, FACT-B PWB decreased at month 1 before improving at later visits. The mean change from baseline at month 1 with neratinib was –2.9 points and was greater than clinically meaningful thresholds (2‒3 points); changes at later time-points were all less than the clinically meaningful threshold.

In the CONTROL study, decreases in FACT-B PWB were observed in all CONTROL cohorts throughout study treatment, with largest changes from baseline observed at month 1. In the loperamide alone and colestipol plus loperamide cohorts, changes reached clinically meaningful thresholds (2‒3 points) at 4 out of 5 study visits, whereas in the budesonide plus loperamide cohort, changes crossed the CID threshold during months 1 and 3 only.

Suzette Delaloge, MD, Institut Gustave Roussy, Paris, France, said, "Diarrhea is the main side effect of neratinib and can be bothersome in some patients. Although this is not a direct comparison, the confrontation of Extenet and Control data teach us how to prevent grade 3 diarrhea and how to allow better quality of life, together with better adherence of patients to this therapy."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased with the HRQoL data from ExteNET and CONTROL. We look forward to additional data from the CONTROL trial, which may continue to improve HRQoL and adherence to treatment."

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 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.