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
drug neratinib are being presented at the 2018 San Antonio Breast Cancer
Symposium (SABCS) that is currently taking place in San Antonio, Texas.
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.
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.
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Table 1: HER2-Mutant, HR-Positive Metastatic Breast Cancer
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Phase II SUMMIT Trial Efficacy Summary
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Neratinib + Fulvestrant
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Subgroups
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All Patients
(n=47)
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Prior Fulvestrant
(n=25)
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Prior CDK4/6 Inhibitor-Based
Therapy (n=20)
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Efficacy Endpoint
a
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Objective response (confirmed)b – n
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14
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4
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6
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CR
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4
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0
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1
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PR
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10
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4
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5
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Objective response rate (95% CI)
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30 (17–45)
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16 (5–36)
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30 (12–54)
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Medianc DOR, months (95% CI)
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9.2 (5.5–16.6)
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DOR for each responder
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9.2; 9.3*; 14.8*; 16.6
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4.5; 7.3; 9.2*; 9.3*; 11.2*; 14.8*
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Clinical benefitd – n
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22
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9
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8
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CR or PR
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14
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4
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6
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SD
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8
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5
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2
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Clinical benefit rate (95% CI)
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47 (32–62)
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36 (18–58)
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40 (19–64)
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Medianc PFS (95% CI) time to event, months
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5.4 (3.7–9.2)
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3.7 (3.5–6.9)
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4.1 (1.9–10.9)
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Patients with RECIST v1.1 Measurable Disease
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Subgroups
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Efficacy Endpoint
a
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All Patients
(n = 39)
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Prior Fulvestrant
(n = 21)
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Prior CDK4/6 Inhibitor-Based
Therapy (n=15)
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Objective response (confirmed)b – n
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12
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4
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5
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CR
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2
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0
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0
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PR
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10
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4
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5
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Objective response rate (95% CI)
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31 (17–48)
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19 (5–42)
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33 (12–62)
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Medianc DOR, months (95% CI)
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9.0 (4.5–16.6)
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DOR for each responder
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9.2; 9.3*; 14.8*; 16.6
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4.5; 7.3; 9.2*; 9.3*; 14.8*
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Clinical benefitd – n
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18
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8
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6
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CR or PR
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12
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4
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5
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SD
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6
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4
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1
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Clinical benefit rate (95% CI)
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46 (30–63)
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38 (18–62)
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40 (16–68)
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Medianc PFS (95% CI) time to event, months
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5.4 (3.5–10.3)
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NA
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NA
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a
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Response is based on investigator tumor assessments per RECIST
v1.1 or modified PERCIST for patients with only PET-evaluable
lesions.
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b
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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.
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c
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Kaplan-Meier analysis
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d
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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).
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*
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Patient still on treatment at time of data cut; DOR, duration of
response; PFS, progression free survival; NA, not available
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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.”
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. Puma in-licenses the global development and
commercialization rights to three drug candidates — PB272 (neratinib,
oral), PB272 (neratinib, intravenous) and PB357. Neratinib, oral was
approved by the U.S. Food and Drug Administration in July 2017 for the
extended adjuvant treatment of adult patients with early stage
HER2-overexpressed/amplified 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. NERLYNX is a registered trademark of Puma
Biotechnology, Inc.
Further information about Puma Biotechnology may be found at www.pumabiotechnology.com.
Forward-Looking Statements
This press release contains forward-looking statements, including
statements regarding the development of combinations involving
neratinib. All forward-looking statements involve risks and
uncertainties that could cause Puma’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 risk factors
disclosed in the reports filed by Puma with the Securities and Exchange
Commission from time to time, including Puma’s Annual Report on Form
10-K for the year ended December 31, 2017. Readers are cautioned not to
place undue reliance on these forward-looking statements, which speak
only as of the date hereof. Puma assumes no obligation to update these
forward-looking statements, except as required by law.
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