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Puma Biotechnology Presents Interim Results of Phase II CONTROL Trial of Neratinib in Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer at the 2019 SABCS

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Puma Biotechnology, Inc. (NASDAQ:PBYI), a biopharmaceutical company, will present updated interim results from a Phase II clinical trial of Puma's drug neratinib at the 2019 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas. The presentation entitled, "Effect of prophylaxis or neratinib dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2-positive early-stage breast cancer: Phase II CONTROL trial," will be displayed at a poster session on December 13 at 5:00 p.m. CST. A full copy of the poster is available on the Puma Biotechnology website.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20191213005405/en/

CONTROL Trial Poster at SABCS 2019 (Graphic: Business Wire)

CONTROL Trial Poster at SABCS 2019 (Graphic: Business Wire)

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.

The main adverse event seen to date in clinical trials of neratinib is diarrhea and, more specifically, grade 3 diarrhea. In the Phase III ExteNET trial of neratinib as extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with adjuvant Herceptin, prophylactic use of anti-diarrheal medications was not mandatory. In the trial, 95.4% of the patients experienced all grade diarrhea and 39.8% of the patients experienced grade 3 or higher diarrhea (there was one event of grade 4 diarrhea). The median cumulative duration of grade 3 diarrhea in the ExteNET trial was 5 days and 16.8% of patients who received neratinib in the ExteNET trial discontinued the drug due to diarrhea.

The CONTROL trial is an international, open-label, Phase II study investigating the use of antidiarrheal prophylaxis or dose escalation in the reduction of neratinib-associated diarrhea that has a primary endpoint of the incidence of grade 3 diarrhea.

In the CONTROL trial, patients with HER2-positive early stage breast cancer who had completed trastuzumab-based adjuvant therapy received neratinib daily for a period of one year. The trial initially tested high dose loperamide prophylaxis given for the first 2 cycles (56 days) of treatment (12 mg on days 1-14, 8 mg on days 15-56 and as needed thereafter). The CONTROL trial was then expanded to include four additional cohorts. One cohort received the combination of loperamide and budesonide, the second cohort received the combination of loperamide plus colestipol, the third cohort received colestipol plus loperamide as needed and the fourth cohort did not use any antidiarrheal drugs as mandatory prophylaxis but instead used a dose escalation during the first month of neratinib treatment. Budesonide is a locally acting corticosteroid that Puma believes targets the inflammation identified in a preclinical model of neratinib-induced diarrhea and colestipol is a bile acid sequestrant that Puma believes targets potential bile acid malabsorption that could result from such inflammation. The dose escalation involved treating with neratinib at 120 mg per day for the first week, 160 mg per week for the second week and 240 mg per week starting at week 3 and until the end of treatment.

The interim analysis of the CONTROL trial presented in the poster included a total of 137 patients who received neratinib plus loperamide prophylaxis, 64 patients who received neratinib plus loperamide prophylaxis for 2 cycles and budesonide for 1 cycle, 136 patients who received neratinib plus loperamide prophylaxis for 1 cycle and colestipol for 1 cycle, 104 patients who received colestipol for 1 cycle and loperamide as needed and 60 patients who received the dose escalation regimen of neratinib.

The results of the trial showed that the incidence of grade 3 diarrhea for the 137 patients who received the loperamide prophylaxis was 31% and that for the 137 patients in this cohort, 20% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3 days.

For the 64 patients who received the combination of loperamide plus budesonide, the results of the trial showed that the incidence of grade 3 diarrhea was 28% and that for the 64 patients in this cohort, 11% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 2.5 days.

For the 136 patients who received the combination of loperamide plus colestipol, the results of the trial showed that the incidence of grade 3 diarrhea was 21% and that for the 136 patients in this cohort, 4% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3.5 days.

For the 104 patients who received colestipol and loperamide as needed, the results of the trial showed that the incidence of grade 3 diarrhea was 34% and that for the 104 patients in this cohort, 8% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3 days.

For the 60 patients who received no antidiarrheal drugs as mandatory prophylaxis and dose escalation of neratinib in the first month, the results of the trial showed that the incidence of grade 3 diarrhea was 15% and that for the 60 patients in this cohort, 3% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 2 days.

Further information is provided in Table 1 below:

Table 1: Incidence of Treatment-Emergent Diarrhea

 

 

 

 

 

 

Neratinib dose

 

 

Budesonide +

 

Colestipol +

 

Colestipol +

 

escalation +

Loperamide

 

loperamide

 

loperamide

loperamide prn

 

loperamide prn

(n=137)

 

(n=64)

 

(n=136)

 

(n=104)

 

(n=60)

 

Treatment-emergent diarrhea incidence, n (%)

No diarrhea

28 (20)

 

9 (14)

 

23 (17)

 

5 (5)

 

2 (3)

Grade 1

33 (24)

 

16 (25)

 

38 (28)

 

33 (32)

 

24 (40)

Grade 2

34 (25)

 

21 (33)

 

47 (35)

 

31 (30)

 

25 (42)

Grade 3

42 (31)

 

18 (28)

 

28 (21)

 

35 (34)

 

9 (15)

Grade 4

0

 

0

 

0

 

0

 

0

 

 

 

 

 

 

 

 

 

Diarrhea leading to discontinuation

28 (20.4)

 

7 (10.9)

 

5 (3.7)

 

8 (7.7)

 

2 (3.3)

 

 

 

 

 

 

 

 

 

Hospitalization (due to diarrhea)

2 (1.5)

 

0

 

0

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