TESARO Announces Data Presentations at ESMO 2018 Congress
TESARO, Inc. (NASDAQ: TSRO), an oncology-focused biopharmaceutical
company, today summarized updated Phase 1 GARNET data of TSR-042
(anti-PD-1 antibody) in patients with recurrent or advanced
microsatellite instability high (MSI-H) endometrial cancer
presented during the European Society for Medical Oncology (ESMO)
Congress. Blinded, pooled interim safety data from the Phase 3
PRIMA trial of niraparib in patients with first-line ovarian cancer
regardless of biomarker status were also presented in a poster
discussion session and additional data from the QUADRA trial of
niraparib for treatment of late-line ovarian cancer beyond BRCAmut
were presented in a poster display.
“The updated results from GARNET presented at
ESMO demonstrate robust clinical activity of TSR-042 in patients
with MSI-H endometrial tumors,” said Mary Lynne Hedley, Ph.D.,
President and COO of TESARO. “In addition, blinded, pooled interim
safety data from the ongoing PRIMA study of niraparib as
maintenance therapy in first line ovarian cancer demonstrated a
favorable tolerability profile for niraparib when dosed according
to a patient’s weight and platelet count compared to a fixed
starting dose. These prospective data confirmed that adverse events
are reduced for patients starting niraparib at an individualized
dose, including a reduction in symptomatic events that are
particularly meaningful to patients. We look forward to announcing
top-line results for the PRIMA study in late 2019.”
TSR-042 (anti-PD-1
antibody)
GARNET: Efficacy data indicates robust
activity of TSR-042 in patients with MSI-high endometrial
cancerGARNET is a multicenter, open-label, Phase 1
dose-escalation study designed to assess the safety,
pharmacokinetics, pharmacodynamics, and clinical activity of
TSR-042 in patients with advanced solid tumors. The weight-based
dose escalation and fixed-dose safety portions of the GARNET study
have been completed. The ongoing cohort expansion portion of GARNET
is evaluating TSR-042 at a dose of 500 milligrams every 3 weeks
(Q3W) for the first 4 cycles, and 1000 milligrams every 6 weeks
(Q6W) thereafter in four cohorts: MSI-H endometrial cancer, MSI-H
non-endometrial cancer, MSS endometrial cancer and non-small cell
lung cancer (NSCLC). Data presented at ESMO included safety and
efficacy data from the cohort of patients with MSI-H endometrial
cancer.
At the time of data cutoff, 35 patients with
MSI-H endometrial cancer had received treatment with TSR-042. Among
the 25 patients with MSI-H endometrial cancer who had at least one
post-baseline tumor assessment, one had a complete response and 12
had partial responses (including 1 unconfirmed response) by immune
related RECIST (irRECIST) criteria (ORR 52%). Twelve of the 13
responses are ongoing (92%), including three patients with partial
responses who have thus far received over 60 weeks of treatment
with TSR-042. Three additional patients (12%) had stable disease.
Median duration of response was not reached.
Preliminary safety findings among the 35 MSI-H
endometrial patients indicate TSR-042 is generally
well-tolerated. Grade ≥3 treatment-related treatment-emergent
adverse events (TEAEs) were reported in 4 out of 35 patients
(11.4%).
The data support the unique and convenient dose
of TSR-042 of 500 mg Q3W for the first 4 doses, then 1000 mg Q6W
thereafter. At this dose, TSR-042 maintained serum concentrations
required to retain maximum receptor occupancy throughout
the dosing cycle.
The GARNET study is intended to support a
Biologics License Application (BLA) submission to the U.S. Food and
Drug Administration (FDA) in 2019.
ZEJULA (niraparib)
PRIMA: Prospective validation of
individualized niraparib dose regimen based on patient baseline
body weight & platelet counts; Rates of adverse events in
blinded, pooled patient groups decreased with individualized
starting dose compared to fixed starting dosePRIMA is a
double-blind, randomized Phase 3 study designed to evaluate
niraparib versus placebo as maintenance therapy in first-line
ovarian cancer patients. Platinum responsive patients were
initially randomized 2:1 to start niraparib at 300 mg once-daily or
placebo and the protocol was subsequently amended to require an
individualized starting dose of 200 mg once-daily in patients with
baseline weight <77kg or platelet count <150K/μL and 300 mg
in all other patients. The trial remains blinded for efficacy and
safety.
Among the 727 patients dosed on the study, 480
patients were treated with a fixed 300 mg starting dose of
niraparib or placebo and 247 patients were treated with an
individualized dose of 300 mg or 200 mg of niraparib based on
weight and platelet count or placebo. The findings presented were
from evaluable patients with ≥30 days of safety data from blinded
pooled niraparib and placebo and indicate improved tolerability
with niraparib at the individualized starting dose. TEAEs grade ≥ 3
were lower (36%) in the individualized dosing group (pooled
niraparib and placebo) as compared with the group that received a
fixed starting dose of 300 mg of niraparib or placebo (52.7%).
There were fewer dose reductions and dose discontinuations in
patients treated with the individualized starting dose compared
with the fixed starting dose. TEAEs leading to treatment
discontinuation remained low for both groups at 7.9% for the fixed
starting dose and 5.3% for the individualized starting dose
group.
The rates of hematologic toxicities of all
grades, including grade ≥ 3, were lower with introduction of an
individualized starting dose. Grade ≥3 non-hematologic toxicities
(nausea, vomiting, fatigue, hypertension, and insomnia) decreased
with an individualized starting dose.
QUADRA: Clinical benefit of niraparib
treatment demonstrated in late-line ovarian cancer setting,
including patients with platinum resistant and refractory
diseaseLate line ovarian cancer represents a high unmet
medical need and efficacy of cytotoxic chemotherapy is limited in
patients with heavily-pretreated ovarian cancer. Previous studies
have shown meaningful activity of other PARP inhibitors in the
late-line treatment of ovarian cancer only in populations with BRCA
mutations. QUADRA, a single arm study, was conducted to assess the
activity of ZEJULA monotherapy in the fourth-line or later
treatment of patients with ovarian cancer, regardless of platinum
sensitivity or biomarker status.
Niraparib treatment demonstrated durable
clinical activity in late-line (≥ 4th line) patients with BRCAmut
tumors, with an ORR of approximately 30%, including patients with
platinum-sensitive, -resistant, and -refractory disease, and a
median duration of response of 9.2 months. The clinical benefit
rate (CBR; CR+PR+SD) at 16 weeks and 24 weeks were 56% and 38%,
respectively. A gradient of clinical activity based on platinum
sensitivity was demonstrated in the BRCAmut patient population,
with greatest activity demonstrated in patients with
platinum-sensitive disease (ORR 39%), mOS was not reached (95% CI
19, NE). However, even patients with platinum-resistant and
platinum-refractory disease experienced benefit from niraparib
treatment with ORR of 33% and 19%, and mOS of 26.0 and 23.3 months,
respectively.
Clinical benefit of niraparib extended beyond
patients with BRCA mutations in this late-line setting. Patients
with non-BRCAmut/HRDpos platinum-sensitive disease had an ORR of
20%. In total, the biomarker-driven population (BRCAmut regardless
of platinum status and non-BRCAmut HRDpos platinum-sensitive
patients) included 98 patients with ORR of 26%, mDOR of 8.3 months,
and a mOS of 23.3 months.
The safety profile in the QUADRA treatment study
was consistent with the safety profile observed in the NOVA
maintenance population.
Details of TESARO’s poster presentations
are as follows (all times local):
ZEJULA® (niraparib)
Saturday, October 20, 2018, 9:15 AM – 10:45 AM; Lecture time:
9:59 AM
A prospective evaluation of tolerability of niraparib dosing
based upon baseline body weight (wt) and platelet (plt) count:
Blinded pooled interim safety data from the PRIMA Study
Poster Discussion, Abstract: 941PD, Location: ICM – Room 13,
Poster Displayed: Hall B4
Saturday, October 20, 2018, 12:30 PM – 1:30 PM
QUADRA: A phase 2, open-label, single-arm study to evaluate
niraparib in patients with relapsed ovarian cancer in 4th or later
line of therapy: results from the BRCAmut subset
Poster Session, Abstract: 944P, Location: Hall A3
Saturday, October 20, 2018, 12:30 PM – 1:30 PM
OVARIO: A single-arm, open-label phase 2 study of maintenance
therapy with niraparib + bevacizumab in patients with advanced
ovarian cancer after response to frontline platinum-based
chemotherapy
Poster Session, Abstract: 999TiP, Location: Hall A3
Saturday, October 20, 2018, 12:30 PM – 1:30 PM
Real world occurrence of top three clinical-trial reported
adverse events of PARP inhibitor niraparib maintenance therapy in
platinum-sensitive recurrent ovarian cancer, a national
retrospective observational study of a 200 mg/day starting-dose
cohort
Poster Session, Abstract: 986P, Location: Hall A3
Saturday, October 20, 2018, 12:30 PM – 1:30 PM
Brain metastases in primary ovarian cancer: real-world data
Poster Session, Abstract: 946P, Location: Hall A3
TSR-042 (anti-PD-1)
Saturday, October 20, 2018, 9:15 AM – 10:45 AM; Lecture
time: 9:15 AM
Preliminary safety, efficacy, and PK/PD characterization from
GARNET, a phase 1 clinical trial of the anti–PD-1 monoclonal
antibody, TSR-042, in patients with recurrent or advanced MSI-H
endometrial cancer
Poster Discussion, Abstract: 935PD, Location: ICM – Room 13,
Poster displayed: Hall B4
Niraparib is marketed in the United States and
Europe under trade name ZEJULA®.
About ZEJULA (Niraparib)ZEJULA
(niraparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor
indicated in the United States and in the EU for the maintenance
treatment of adult patients with recurrent epithelial ovarian,
fallopian tube, or primary peritoneal cancer who are in a complete
or partial response to platinum-based chemotherapy. In preclinical
studies, ZEJULA concentrates in the tumor relative to plasma,
delivering greater than 90% durable inhibition of PARP 1/2 and a
persistent antitumor effect. Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML),
including some fatal cases, was reported in 1.4% of patients
receiving ZEJULA vs 1.1% of patients receiving placebo in Trial 1
(NOVA), and 0.9% of patients treated with ZEJULA in all clinical
studies. The duration of ZEJULA treatment in patients prior to
developing MDS/AML varied from <1 month to 2 years. All patients
had received prior chemotherapy with platinum and some had also
received other DNA damaging agents and radiotherapy. Discontinue
ZEJULA if MDS/AML is confirmed.
Hematologic adverse reactions (thrombocytopenia, anemia and
neutropenia) have been reported in patients receiving ZEJULA. Grade
≥3 thrombocytopenia, anemia and neutropenia were reported in 29%,
25%, and 20% of patients receiving ZEJULA, respectively.
Discontinuation due to thrombocytopenia, anemia, and neutropenia
occurred, in 3%, 1%, and 2% of patients, respectively. Do not start
ZEJULA until patients have recovered from hematological toxicity
caused by prior chemotherapy (≤ Grade 1). Monitor complete blood
counts weekly for the first month, monthly for the next 11 months
of treatment, and periodically thereafter. If hematological
toxicities do not resolve within 28 days following interruption,
discontinue ZEJULA, and refer the patient to a hematologist for
further investigations.
Hypertension and hypertensive crisis have been reported in
patients receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of
patients receiving ZEJULA vs 2% of patients receiving placebo in
Trial 1, with discontinuation occurring in <1% of patients.
ZEJULA can cause fetal harm and females of reproductive potential
should use effective contraception.
In clinical studies, the most common adverse reactions (Grades
1-4) in ≥10% of patients included: thrombocytopenia (61%), anemia
(50%), neutropenia (30%), leukopenia (17%), palpitations (10%),
nausea (74%), constipation (40%), vomiting (34%), abdominal
pain/distention (33%), mucositis/stomatitis (20%), diarrhea (20%),
dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased
appetite (25%), urinary tract infection (13%), aspartate
aminotransferase (AST)/alanine aminotransferase (ALT) elevation
(10%), myalgia (19%), back pain (18%), arthralgia (13%), headache
(26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety
(11%), nasopharyngitis (23%), dyspnea (20%), cough (16%), rash
(21%) and hypertension (20%).
Common lab abnormalities (Grades 1-4) in ≥25% of patients
included: decrease in hemoglobin (85%), decrease in platelet count
(72%), decrease in white blood cell count (66%), decrease in
absolute neutrophil count (53%), increase in AST (36%) and increase
in ALT (28%). Please see full U.S. prescribing information,
including additional important safety information, available at
www.zejula.com.
About GARNETThe ongoing Phase I
GARNET trial is evaluating TSR-042 as monotherapy in patients with
advanced solid tumors. GARNET included a weight-based dose
escalation study (Part 1) and a fixed-dose safety study (Part 2A),
both of which have been completed. Results of these studies were
used to determine the recommended Phase 2 dose (RP2D; 500 mg Q3W
for the first 4 cycles then 1000 mg Q6W). The study is now
enrolling patients with MSI-H endometrial cancer, MSI-H
non-endometrial cancer, MSS endometrial cancer, and NSCLC into four
large expansion cohorts.
About TSR-042
TSR-042 is an investigational humanized
anti-programmed death (PD)-1 monoclonal antibody that binds with
high affinity to the PD-1 receptor and effectively blocks its
interaction with the ligands PD-L1 and PD-L2. TSR-042 is the only
anti-PD-1 therapy administered as monotherapy every 3 weeks for 4
doses then every 6 weeks thereafter. TSR-042 was developed as part
of the collaboration between TESARO and AnaptysBio, Inc. This
collaboration was initiated in March of 2014, and is focused on the
development of monospecific antibody drugs targeting PD-1, TIM-3
(TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific
antibody drug candidate targeting PD-1/LAG-3 (TSR-075).
About TESAROTESARO is an
oncology-focused biopharmaceutical company devoted to providing
transformative therapies to people facing cancer. For more
information, visit www.tesarobio.com, and follow us on Twitter and
LinkedIn.
Investor/Media Contact:Kate
RauschDirector, Investor Relations+1.781.257.2505 or
krausch@tesarobio.com
To the extent that statements contained in this
press release are not descriptions of historical facts regarding
TESARO, they are forward-looking statements reflecting the current
beliefs and expectations of management made pursuant to the safe
harbor provisions of the Private Securities Litigation Reform Act
of 1995. Words such as "may," "will," "expect," "anticipate,"
"estimate," "intend," and similar expressions (as well as other
words or expressions referencing future events, conditions, or
circumstances) are intended to identify forward-looking statements.
Examples of forward-looking statements contained in this press
release include, among others, statements regarding the potential
dosing schedule for TSR-042, the expected timing of our clinical
trial readouts, and the expected timing of our planned regulatory
submission for TSR-042 and niraparib. Forward-looking statements in
this release involve substantial risks and uncertainties that could
cause our results, performance, or achievements to differ
significantly from those expressed or implied by the
forward-looking statements. Such risks and uncertainties include,
among others, the uncertainties inherent in the execution and
completion of clinical trials and regulatory submissions,
uncertainties surrounding the timing of availability of data from
clinical trials, uncertainties surrounding potential actions by
regulatory authorities such as the US FDA, risks related to
manufacturing and supply, risks related to intellectual property,
and other matters that could affect our ongoing and planned
development programs, and/or the availability or commercial
potential of our products and product candidates, including
TSR-042. TESARO undertakes no obligation to update or revise any
forward-looking statements. For a further description of the risks
and uncertainties that could cause actual results to differ from
those expressed in these forward-looking statements, as well as
risks relating to the business of the Company in general, see
TESARO's Annual Report on Form 10-K for the year ended December 31,
2017 and Quarterly Report on Form 10-Q for the quarter ended June
30, 2018.
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