CONTROL study results show improved tolerability of NERLYNX® (neratinib) with all the investigated diarrhoea prophylaxis strategies

CASTRES,France,Dec. 10,2021 -- Today,the final findings of the CONTROL study1 were presented at the 2021 San Antonio Breast Cancer Symposium (SABCS). Results suggest that providing a prophylactic anti-diarrhoea medical treatment or applying a dose escalation schedule of neratinib associated with loperamide (as necessary) at treatment initiation over two-weeks reduces the incidence,severity,and duration of neratinib-associated grade 3 diarrhoea.

The improved tolerability allowsHER2+patientswith early breast cancer(eBC)who have previously been treated with trastuzumab-based therapywithin less than 1 yearto stay onneratiniblonger,increasing their ability toreceive the full benefit ofthetherapy.

The CONTROLstudy was committed upon the results oftheExteNETpivotalstudy2,in whichno mandatory anti-diarrhoea therapy was administered andwheregrade ≥3 diarrhoea was observed innearly 40% of patients and 17% of patients discontinuedthe studyfor this specific reason.

The CONTROLstudy(n= 563)was designed toinvestigatesixprophylaxisoptionsfor the prevention ofneratinibassociated diarrhoea.Final results presented at SABCS determined that adoption ofneratinibdose escalationinassociation withloperamide (as necessary) during the first two-weeks of treatment (DE1 cohort) was associated with the lowest rate of grade3 diarrhoea during the trial compared with all otherinvestigatedanti-diarrheal strategies.At least 75% of patients receivedneratiniblonger than 11.06 months in the DE1 cohort,compared with 7.46 months in the DE2 cohort,which comprised of patients taking neratinib over a4-week escalationand loperamide (as necessary).The DE1 cohort alsoreportedthe lowest rate of diarrhoea-related discontinuations (3.3%) and dose holds (11.7%).

DeborahSzafir,Executive Vice President,Medical & PatientConsumerDepartmentDirectorsaid,"The CONTROL study has showed that neratinib associated diarrhoea can be managed with proactive prophylaxis and dose escalation strategies. These results provide useful information to the scientific community about neratinib safety profile and its management. This is an important outcome as we know that,despite the advances offered by the many anti-HER2 agents available for early breast cancer treatment,up to 25% of HER2+ patients will still experience a recurrence of the disease at 10 years."

The CONTROL study final results were submitted to the European Medicines Agency in order to align the Product Information with the current scientific knowledge.

REFERENCES

1Abstract P5-18-02-Chan A.Final findings from the CONTROL trial of diarrheal prophylaxis or neratinib dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2+ early-stage breast cancer – 2021 SABCS,Poster Session 5,Friday,7:00-8:30 a.m. CT

2Chan A,DelalogeS,Holmes FA,et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): amulticentre,randomised,double-blind,placebo-controlled,phase 3 trial. Lancet Oncol. 2016;17:367e377.

NOTES TO EDITOR

About CONTROL-NCT02400476

The CONTROL trialis sponsored byPumaBiotechnology,Inc.. It isan international,multi-cohort,open-label,phase 2 study designed toinvestigate6preventive antidiarrheal prophylaxisoptionswith loperamidefor the prevention of neratinib associateddiarrhoea.Adult patients (563)with stageI–IIIc HER2+ breast cancer who had completed trastuzumab-based adjuvant therapy within 1-year prior to study entryreceived oral neratinib (240 mg/day for 1 year).

The patients wereenrolled sequentially intosixseparate cohorts:

Mandatory loperamide prophylaxis.

Budesonide + loperamide.

Colestipol + loperamide.

Colestipol + loperamidepro re nata (PRN).

Neratinib DE1 (2-week escalation) + loperamide(PRN,as necessary).

Neratinib DE2 (4-week escalation) + loperamide(PRN,as necessary).

AboutExteNET-NCT00878709

ExteNETwas a multicentre,placebo-controlled phase III trial.Patients withHER2+eBCreceived oral neratinib 240 mg/day or placebo for 12 months after trastuzumab-based (neo)adjuvant therapy.TheExteNETtrialmet its primary endpoint anddemonstrated improved invasive disease-free survival (iDFS) withNERLYNX,compared withplacebo in patients withHER2+eBC.The greater and more durable efficacy was observed in the subgroup with HR+ disease who initiated treatment withinoneyear of completing trastuzumab,referred to as the HR+/≤ 1 year population,leading to the EMAlabel population.

AboutNERLYNX®

NERLYNX®(neratinib) is a type of targeted therapy for breast cancer called an irreversible pan-HER inhibitor(it inhibitsHER1,HER2 & HER4). It is a once daily oral tablets treatmentapprovedin Europeto treat adults with early-stage human epidermal growth factor receptor 2 positive (HER2+)and hormone receptor positive (HR+)breast cancer who have previously been treated with trastuzumab-based therapywithin less than 1 year.

Neratinibworks blocking the HER2 receptors on the surface of breast cancer cells from receiving growth signals and helps to stop the cancer from spreading.

NERLYNX®is a registered trademark of Puma Biotechnology,Inc.Puma in-licenses the global development and commercialization rights to PB272 (neratinib,oral),PB272 (neratinib,intravenous) and PB357.

Pumagranted Pierre Fabre exclusive rights to develop and commercialize NERLYNXwithin Europe,Turkey,Middle East,Africa and Greater China.

For further information,please visit the Pierre Fabre website at www.pierre-fabre.com,@PierreFabre

ContactPierre Fabre

AnneKerveillant

anne.kerveillant@pierre-fabre.com