LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company,
announced that results from an ongoing Phase II clinical trial of Puma's
investigational drug PB272 (neratinib) were presented at the 2017
American Association for Cancer Research Annual Meeting (AACR) that is
currently taking place in Washington, D.C. The presentation entitled,
“Neratinib in HER2 or HER3 mutant solid tumors: SUMMIT, a global,
multi-histology, open-label, phase 2 ‘basket’ study,” was presented as a
plenary session by David Hyman, M.D., Director of Developmental
Therapeutics at Memorial Sloan Kettering Cancer Center (MSK), and
principal investigator of the trial.
The Phase II SUMMIT basket trial is an open-label, multicenter,
multinational study to evaluate the safety and efficacy of PB272
administered daily to patients who have solid tumors with activating
HER2 or HER3 mutations. All patients received loperamide (16 mg per day
initially) prophylactically for the first cycle of treatment in order to
reduce the neratinib-related diarrhea.
Included in the presentation were data on 141 patients enrolled in the
neratinib monotherapy arm of the trial, including 124 patients with HER2
mutations and 17 patients with HER3 mutations. This included
patients with 21 unique tumor types, with the most common being breast,
lung, bladder and colorectal cancer. There were also 30 distinct HER2
and 12 distinct HER3 mutations observed among these patients, with the
most frequent HER2 variants involving S310, L755, A755_G776insYVMA and
V777.
In the HER2-mutant cohort, clinical responses were observed in
tumors with S310, L755, V777, P780_Y781insGSP and A775_G776insYVMA
mutations. When stratified by tumor type, responses were observed in
patients with breast, cervical, biliary, salivary and non-small-cell
lung cancers, which led to cohort expansions in these tumor types. No
activity was observed in the HER3-mutant cohort. A more detailed
presentation of the data is presented in Table 1 below and a copy of the
full presentation is available on the Puma Biotechnology website.
|
Table 1: SUMMIT Trial Efficacy Summary
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
HER2
mut
|
|
HER2
mut
|
|
HER2
mut
|
|
HER2
mut
|
|
HER2
mut
|
|
HER2
mut
|
|
HER3
mut
|
|
|
Breast
|
|
Bladder
|
|
Lung
|
|
Colorectal
|
|
Biliary tract
|
|
Cervical
|
|
NOS
|
|
|
(n=25)
|
|
(n=16)
|
|
(n=26)
|
|
(n=12)
|
|
(n=9)
|
|
(n=5)
|
|
(n=17)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
ORR at week 8,
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
n (%)
|
|
8 (32.0)
|
|
0 (0.0)
|
|
1 (3.8)
|
|
0 (0.0)
|
|
2 (22.2)
|
|
1 (20.0)
|
|
0 (0.0)
|
(95% CI)
|
|
(14.9--53.5)
|
|
(0.0--20.6)
|
|
(0.1--19.6)
|
|
(0.0--26.5)
|
|
(2.8--60.0)
|
|
(0.5--71.6)
|
|
(0.0--20.6)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Clinical benefit
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
rate, n (%)
|
|
10 (40.0)
|
|
3 (18.8)
|
|
11 (42.3)
|
|
1 (8.3)
|
|
3 (33.3)
|
|
3 (60.0)
|
|
2 (11.8)
|
(95% CI)
|
|
(21.1--61.3)
|
|
(4.0--45.6)
|
|
(23.4--63.1)
|
|
(0.2--38.5)
|
|
(7.5--70.1)
|
|
(14.7--94.7)
|
|
(1.6--38.3)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Median PFS,
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
months
|
|
3.5
|
|
1.8
|
|
5.5
|
|
1.8
|
|
2.8
|
|
20.1
|
|
1.7
|
(95% CI)
|
|
(1.9--4.3)
|
|
(1.7--3.5)
|
|
(2.7--10.9)
|
|
(1.4--1.9)
|
|
(0.5--3.7)
|
|
(0.5--NA)
|
|
(1.4--2.0)
|
The neratinib safety profile observed in the SUMMIT study is 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 141 patients enrolled in the neratinib monotherapy arm
with safety data available, 31 patients (22%) reported grade 3 diarrhea.
The median duration of grade 3 diarrhea for those patients was 2 days. 4
patients (2.8%) permanently discontinued neratinib due to diarrhea and
21 patients (14.9%) temporarily discontinued neratinib due to diarrhea
and then restarted after the diarrhea subsided.
Dr. David Hyman stated, "Neratinib showed signs of clinical activity in
several of the cohorts in the SUMMIT trial. 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
enrollment in the ongoing cohorts in the study and continuing to utilize
the basket trial design to explore possible treatment options for these
select patient populations.”
"The basket-trial design we are utilizing for SUMMIT is enabling us to
evaluate the clinical potential of neratinib in patients with specific
mutation-types rather than limiting exploration to one tumor type at a
time. It is an efficient approach that is generating clinically
meaningful information to guide targeted therapy across a broad spectrum
of tumor types with HER mutations, including in patients with rare
tumors who may not otherwise have access to investigational therapies,”
said Alan H. Auerbach, Chief Executive Officer and President of Puma
Biotechnology. “We are very pleased with the preliminary activity seen
with neratinib in the SUMMIT trial. We look forward to advancing this
targeted compound into further clinical development in multiple HER2
mutant tumor types, both as monotherapy and in novel combinations."
About Puma Biotechnology
Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on
the development and commercialization of innovative products to enhance
cancer care. The Company in-licenses the global development and
commercialization rights to three drug candidates—PB272 (neratinib
(oral)), PB272 (neratinib (intravenous)) and PB357. Neratinib is a
potent irreversible tyrosine kinase inhibitor that blocks signal
transduction through the epidermal growth factor receptors, HER1, HER2
and HER4. Currently, the Company is primarily focused on the development
of the oral version of neratinib, and its most advanced drug candidates
are directed at the treatment of HER2-positive breast cancer. The
Company believes that neratinib has clinical application in the
treatment of several other cancers as well, including non-small cell
lung cancer and other tumor types that over-express or have a mutation
in HER2. Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.
Forward-Looking Statements:
This press release contains forward-looking statements, including
statements regarding the development of the Company’s drug candidates.
All forward-looking statements included in this press release involve
risks and uncertainties that could cause the Company's actual results to
differ materially from the anticipated results and expectations
expressed in these forward-looking statements. These statements are
based on current expectations, forecasts and assumptions, and actual
outcomes and results could differ materially from these statements due
to a number of factors, which include, but are not limited to, the fact
that the Company has no product revenue and no products approved for
marketing; the Company's dependence on PB272, which is still under
development and may never receive regulatory approval; the challenges
associated with conducting and enrolling clinical trials; the risk that
the results of clinical trials may not support the Company's drug
candidate claims; even if approved, the risk that physicians and
patients may not accept or use the Company's products; the Company's
reliance on third parties to conduct its clinical trials and to
formulate and manufacture its drug candidates; the Company's dependence
on licensed intellectual property; and the other risk factors disclosed
in the periodic and current reports filed by the Company with the
Securities and Exchange Commission from time to time, including the
Company's Annual Report on Form 10-K for the year ended December 31,
2016. Readers are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date hereof. The
Company assumes no obligation to update these forward-looking
statements, except as required by law.
Contact: