Biotechnology Events

Home

Puma Biotechnology, Inc.

.

(iv) report data from our Phase II trial of PB272 in HER2 non-amplified breast cancer that has a HER2 mutation (anticipated in the second half of 2015)
More
Source: press release, 5/11/15. http://www.pumabiotechnology.com/pr20150511.html

.
“We expect our research productivity to continue in 2015. In 2015, we expect to (i) present and publish the Phase III ExteNET trial results of PB272 in the extended adjuvant treatment of early stage HER2-positive breast cancer (anticipated in mid-2015); (ii) present and publish the Phase II NEfERTT trial results of PB272 as a first-line treatment for HER2-positive locally recurrent or metastatic breast cancer (anticipated in mid-2015); (iii) complete our ongoing Phase II FB-7 trial of PB272 as a neoadjuvant treatment for patients with HER2-positive breast cancer (anticipated in the first half of 2015); (iv) initiate our Phase II trial of neratinib monotherapy with high dose loperamide prophylaxis in the extended adjuvant treatment of early stage HER2-positive breast cancer (anticipated in the first quarter of 2015); (v) expand additional cohorts in our Phase II basket trial of PB272 in patients with solid tumors with an activating HER2-mutation (anticipated in the first half of 2015); (vi) complete the ongoing Phase II trial of PB272 in patients with HER2-positive metastatic breast cancer that has metastasized to the brain, with the potential to report data in the second half of 2015;

(vii) report data from our Phase II trial of PB272 in HER2-negative breast cancer patients who have a HER2 mutation (anticipated in the second half of 2015);

and (viii) initiate a Phase III trial of the combination of PB272 plus temsirolimus in fourth line HER2-positive metastatic breast cancer (anticipated in the second half of 2015).”
More
Source: press release, 3/02/15. http://investor.pumabiotechnology.com/press-release/puma-biotechnology-r...

.

Alan H. Auerbach, CEO, President and Chairman of the Board, commented on results for the phase-II trial of Neratinib in metastatic HER-2 non-amplified but HER-2 mutant Breast cancer. He stated, "We will update on this later this year."
Source: Goldman Sachs 35th Annual Healthcare Conference, 6/12/14.

.

A Phase II Study of Neratinib in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer
Estimated Enrollment: 29
Study Start Date: December 2012
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
More
Source: clinical trials.gov. http://clinicaltrials.gov/ct2/show/NCT01670877?term=neratinib&rank=7

.

Compound/DeviceSpecialtyIndicationCompound ClassTarget
Neratinib (PB-272) MBCOncologyBreast Cancer (metastatic)HER-2 receptor inhibitorHER-2 receptor

Mechanism of action: Neratinib (PB-272) is an orally available, 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile irreversible inhibitor of the HER-2 receptor tyrosine kinase with potential antineoplastic activity. Neratinib binds to the HER-2 receptor irreversibly, thereby reducing autophosphorylation in cells, apparently by targeting a cysteine residue in the ATP-binding pocket of the receptor. Treatment of cells with this agent results in inhibition of downstream signal transduction events and cell cycle regulatory pathways; arrest at the G1-S (Gap 1/DNA synthesis)-phase transition of the cell division cycle; and ultimately decreased cellular proliferation. Neratinib also inhibits the epidermal growth factor receptor (EGFR) kinase and the proliferation of EGFR-dependent cells.

Phase of Development: II

Event Type: Data: Phase II trial results

Dates: 2015-10-01 - 2015-12-31

Results:

.

Puma Biotechnology Presents Interim Results of Phase II Trial of PB272 for ERBB2 Mutant, HER2 Non-Amplified, Metastatic Breast Cancer at the 2015 San Antonio Breast Cancer Symposium

"Neratinib for ERBB2 mutant, HER2 non-amplified, metastatic breast cancer: preliminary analysis from SUMMIT – a multicenter, open-label, multi-histology phase II basket trial"

LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, announced that interim results from an ongoing Phase II clinical trial of Puma's investigational drug PB272 (neratinib) were presented at the 2015 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas. The presentation entitled “Neratinib for ERBB2 mutant, HER2 non-amplified, metastatic breast cancer: preliminary analysis from SUMMIT – a multicenter, open-label, multi-histology phase II basket trial” will be presented as a poster discussion by Dr. David Hyman, Acting Director, Developmental Therapeutics at Memorial Sloan Kettering Cancer Center.

In May 2014 Puma announced that it expanded the first cohort from the Phase II clinical trial of PB272 (neratinib) in patients with solid tumors who have an activating ERBB2 (HER2) mutation (SUMMIT basket trial). These interim results are the first presentation of data from this expanded cohort of patients with metastatic breast cancer and whose tumors have a HER2 mutation but are neither HER2 amplified or overexpressed (HER2 negative).

In the cohort, patients with HER2 mutant metastatic breast cancer were enrolled and received 240 mg of neratinib daily. Patients received loperamide (16 mg per day initially) prophylactically for the first cycle of treatment in order to reduce the neratinib-related diarrhea. For the 20 patients in the cohort presented, 20 patients (100%) had HER2-negative disease, 17 patients (85%) were hormone receptor positive (estrogen receptor or progesterone receptor positive), and patients had received a median of 4 prior regimens in the metastatic setting (range 0-11 prior regimens) before entering the trial.

The primary endpoint of the trial was objective response at week 8 assessed by anatomic or metabolic imaging. The interim efficacy results from the trial showed that for the 19 efficacy evaluable patients in the breast cancer cohort, 6 patients (32%) experienced a response at week 8. This included one patient with a complete response and five patients with partial responses. The secondary endpoints of the trial included confirmed objective response (complete response or partial response), clinical benefit rate and progression free survival (PFS). The results of the trial showed that 3 patients (16%) had a confirmed objective response, 8 patients (42%) demonstrated clinical benefit and the median progression free survival was 4.0 months.

The presentation also discussed that a bidirectional cross-talk between hormone receptor and HER2 signaling pathways can lead to endocrine resistance due to activated HER2 signaling and ER-mediated tumor proliferation as a potential resistance mechanism to sustained HER2 inhibition. Preclinical data has demonstrated that the combination of an anti-estrogen with a HER2 inhibitor results in enhanced anti-tumor activity in preclinical models of estrogen receptor positive/HER2-positive breast tumors. Based on this, the SUMMIT study was amended to allow for the combination of neratinib plus fulvestrant in eligible postmenopausal hormone receptor positive breast cancer patients. For the 3 response-evaluable patients who have been enrolled and received the combination of neratinib plus fulvestrant, 3 (100%) of 3 patients have shown a response, including one patient with a complete response and two patients with partial responses. There have also been two patients enrolled on the combination of neratinib plus fulvestrant after progressing on neratinib monotherapy. One (50%) of these two patients has demonstrated a partial response.

The interim safety results of the study showed that the most frequently observed adverse event was diarrhea. For the 130 patients enrolled across all solid tumor cohorts in the SUMMIT study, 25 patients (19%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for the patients in the entire SUMMIT study was 2 days. 2 patients (2%) in the SUMMIT study have permanently discontinued neratinib due to diarrhea and 20 patients (15%) have temporarily discontinued neratinib due to diarrhea and then restarted after the diarrhea subsided. For the breast cancer mutation cohort, 7 of 20 patients (35%) experienced grade 3 diarrhea. The median duration of grade 3 diarrhea was 1 day. No patient (0%) in the breast cancer cohort permanently discontinued neratinib due to diarrhea and 4 patients (20%) temporarily discontinued neratinib due to diarrhea and then restarted after the diarrhea subsided.

Dr. David Hyman, Acting Director, Developmental Therapeutics at Memorial Sloan Kettering Cancer Center and principal investigator of the trial, stated, "Neratinib showed promising signs of clinical activity as a single agent and very encouraging clinical activity in the patients with the combination of neratinib plus fulvestrant in this interim analysis of pre-treated HER2 mutant breast cancer patients. The safety profile of the drug was manageable and the diarrhea was not treatment-limiting with appropriate prophylaxis and management. We look forward to completing the ongoing neratinib plus fulvestrant cohort and initiating the pivotal trial of the combination that we are currently planning for 2016.”

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are very pleased with the preliminary activity seen with neratinib, both alone and in combination with fulvestrant in this cohort of patients with HER2 mutated breast cancer. We look forward to the completion of the trial and advancing the combination of PB272 and fulvestrant into a pivotal trial in 2016."
More
Source: press release, 12/10/15. http://investor.pumabiotechnology.com/press-release/puma-biotechnology-p...

.