TESARO Summarizes ZEJULA and TSR-042 Data Presented at the 2017 ESMO Annual Meeting
(Thomson Reuters ONE) -
MADRID, Spain, Sept. 11, 2017 (GLOBE NEWSWIRE) -- TESARO, Inc. (NASDAQ:TSRO), an
oncology-focused biopharmaceutical company, today provided a summary of ZEJULA
and TSR-042, an anti-PD-1 antibody, data presented at the 2017 European Society
of Medical Oncology (ESMO) Annual Meeting in Madrid.
"ZEJULA is the market-leading PARP inhibitor, with unsurpassed efficacy in a
broad patient population and convenient, once-daily dosing," said Mary Lynne
Hedley, Ph.D., President and COO of TESARO. "'Watchful waiting' is no longer an
acceptable option for women living with ovarian cancer. We believe combination
approaches, including niraparib and anti-PD-1 antibodies, will become
increasingly important and we are executing on our registration strategy for
TSR-042, our anti-PD-1 antibody, in MSI-high cancers."
ZEJULA (niraparib) presentations:
Treatment with niraparib did not impact patient quality of life in the NOVA
trial
Quality of life measures are important to understanding the benefit of niraparib
in the maintenance treatment setting. Dr. Amit M. Oza, M.D., Senior Staff
Physician, Division of Medical Oncology and Hematology, Princess Margaret Cancer
Centre, University Health Network, presented quality of life (QoL) data from the
Phase 3 ENGOT-OV16/NOVA trial. Patient-reported outcomes (PROs) were evaluated
along with individual patient-reported symptoms using the Functional Assessment
of Cancer Therapy-Ovarian Symptoms Index (FOSI) and European Quality of Life
Scale 5-Dimensions (EQ-5D-5L). The most common PRO symptoms at baseline were
fatigue and pain, and 20% of patients experienced nausea at baseline. No
significant difference in mean patient-reported outcomes (PRO) scores was
observed between patients treated with niraparib versus placebo, regardless of
germline BRCA mutation status. Hematologic adverse events (thrombocytopenia,
neutropenia, anemia) decreased over time with dose modification and did not
impact QoL. These results also suggest that patients with ovarian cancer often
experience residual symptoms of their disease following the conclusion of
chemotherapy.
Safety and efficacy of niraparib in elderly patients comparable to overall
population in NOVA
In a poster discussion session, safety and efficacy results from the ENGOT-
OV16/NOVA trial were highlighted for a sub-group of elderly patients, aged 70
years and older. In this post-hoc analysis, the efficacy of niraparib was
similar for patients aged <70 years compared to patients aged greater than or
equal to 70 years in both the gBRCAmut and non-gBRCAmut cohorts. Grade greater
than or equal to 3 treatment-emergent adverse events (TEAEs) occurring in >10%
of niraparib treated patients were also consistent between the two groups, and
dose reductions, interruptions, and treatment discontinuations occurred with
similar frequency, regardless of age. These results demonstrate that niraparib
may provide clinical benefit to a broad population of patients with ovarian
cancer irrespective of age.
Niraparib exposure - response findings support dosing patients at individually
adjusted maximal tolerated dose
In a poster discussion session, the relationship between niraparib exposure and
efficacy, as well as exposure and safety, was highlighted in patients enrolled
in the ENGOT-OV16/NOVA trial. Efficacy as measured by PFS was compared in
patients with high exposure (defined as greater than median exposure) versus low
exposure (defined as less than or equal to median exposure). Patients
experienced similar efficacy at their individual maximum tolerated dose
regardless of the dose received. Reaching maximal exposure for individual
patients, as was done in the ENGOT-OV16/NOVA trials via dose modifications, was
likely an important factor in achieving maximal efficacy, especially for
patients without a BRCA mutation. Limited exposure-efficacy association was
observed among patients who were germline BRCA mutation carriers, while the
exposure-efficacy association was more apparent for patients who were not
germline BRCA mutation carriers. On a population level, the incidence of
treatment-emergent adverse events (TEAEs) was higher with increased dose. These
findings support that patients, especially those with BRCA wild-type tumors,
should be treated at their individually adjusted maximal tolerated dose to
provide the optimal chance of efficacy.
Model highlights niraparib pharmacokinetic properties, including high tissue
distribution and slow elimination, and no need for dose adjustments in patients
with mild-to-moderate renal or hepatic impairment
In a poster display session, data from the Phase 1 dose-escalation and expansion
studies (n=104) and the Phase 3 ENGOT-OV16/NOVA study (n=408) of niraparib were
used to model the impact of patient variables (age, race, ethnicity, body
weight), renal impairment (normal, mild, or moderate), and hepatic function
(baseline serum alanine and aspartate aminotransferase, albumin, total
bilirubin) on niraparib pharmacokinetic parameters. In the base model, the
typical value for niraparib apparent clearance was 16.2 L/h, with inter-
individual variability of 52.6%. The estimated volume of distribution was 1074 L
(290 L central and 784 L peripheral compartment). None of the patient variables
impacted niraparib pharmacokinetics, including mild-to-moderate renal impairment
and mild hepatic impairment, and model diagnostics showed good agreement between
predicted and observed individual niraparib plasma concentrations. These results
demonstrate that no dose adjustments are needed for patients treated with
niraparib with mild-to-moderate renal or hepatic impairment.
Bevacizumab-niraparib combination demonstrated preliminary evidence of activity
and a predictable adverse event profile
Updated data from the ongoing Phase 2 AVANOVA study of bevacizumab plus
niraparib, an Investigator Supported Trial (IST), in patients with platinum
sensitive recurrent ovarian cancer (n=12) demonstrated activity and a
predictable adverse event profile. In the first cycle (21 days) of the study,
patients experienced expected and manageable adverse events including anemia,
constipation, fatigue, hypertension, nausea and thrombocytopenia. One dose-
limiting toxicity (grade 3 thrombocytopenia) was observed at the highest dose
level. Three patients were dose reduced and two patients terminated bevacizumab.
Preliminary evidence of activity was demonstrated, with a disease control rate
of 92% and response rate of 50%, including 1 CR and 5 PRs. There were five
additional patients with stable disease. The median progression-free survival
(PFS) was 49 weeks. These data support the potential to combine niraparib plus
bevacizumab. Part 2 of the AVANOVA trial continues to enroll patients.
Frequent hospitalizations and ER visits during "watchful waiting" period support
a change in clinical practice to maintenance therapy options for ovarian cancer
patients
A retrospective study was conducted in the U.S. to characterize the treatment-
free interval (or "watchful waiting") for patients newly diagnosed with ovarian
cancer following completion of treatment with platinum-based chemotherapy. The
analysis found that during the "watchful waiting" period, 30.1% of patients were
admitted to the hospital as an in-patient, and 27.4% of patients visited the
emergency room. These results suggest that patients with ovarian cancer often
experience residual symptoms of their disease following the conclusion of
chemotherapy.
Preliminary Phase 2 niraparib/pembrolizumab combination (TOPACIO) data shows
activity in patients with platinum-resistant ovarian and triple-negative breast
cancer
Data from a Phase 1 dose-escalation study of niraparib in combination with
pembrolizumab in patients with platinum-resistant ovarian cancer (OC) or triple
negative breast cancer (TNBC) was presented, along with preliminary response
data from patients thus far treated in the Phase 2 TOPACIO study. In Phase 1,
among the nine evaluable OC patients, five responded (partial or complete
response) and four achieved stable disease. Three of the five responders had
tumors that tested as wildtype BRCA 1/2 and three as PD-L1 negative (<1%). Of
the four evaluable TNBC patients, three had stable disease and one patient came
off study prior to her first assessment. The most common treatment related grade
greater than or equal to 3 adverse events occurring in greater than or equal to
2 patients included anemia (35.7%), thrombocytopenia (35.7%), neutropenia
(14.3%) and decreased platelet counts (14.3%). The recommended Phase 2 dose of
niraparib was established as 200 mg oral niraparib once daily (increasing to
300 mg after cycle 2 in patients with no significant hematologic toxicities) in
combination with 200 mg IV pembrolizumab on day 1 of each 21-day cycle.
The Phase 2 portion of the TOPACIO study is ongoing, and, as of the data cutoff,
36 OC patients and 47 TNBC patients were enrolled out of a planned 48 patients
for each tumor cohort. Twenty-nine OC and 27 TNBC patients have been assessed by
at least one scan with responses observed in both BRCA wild-type and PD-L1
negative tumors. Among the patients who had received at least one on-study scan,
6 OC patients and 5 TNBC patients had a greater than or equal to 30% decrease in
tumor lesion size and 10 of these 11 patients continue on therapy. Overall 52%
OC and 63% TNBC patients who did not have progressive disease continue on
therapy. No new safety signals were identified, and less than 7% of Phase 2
patients had experienced grade greater than or equal to 3 thrombocytopenia
during the first treatment cycle. Thirty patients (36.1%) enrolled in Phase 2
reported treatment-related grade greater than or equal to 3 adverse events
including anemia (8.4%), fatigue (6.0%), platelet count decrease (6.0%) and
thrombocytopenia (6.0%).
TSR-042 (anti-PD-1 antibody)
TSR-042 safety profile and clinical activity demonstrated in heavily pre-treated
patients
In a poster display session, preliminary safety, efficacy, receptor occupancy,
and pharmacokinetic data for TSR-042, an anti-PD-1 antibody, were presented from
a two-part Phase 1 study. No dose limiting toxicities were observed. Adverse
events included fatigue, nausea, arthralgia, decreased appetite, and pruritus,
which occurred in greater than or equal to 10% of patients. In Part 1 (n=21),
two patients with ovarian cancer and small cell lung cancer who were treated
with TSR-042 experienced a partial response and five patients with fallopian
tube or ovarian cancer had stable disease, two of whom are continuing treatment.
Consistent with data reported for other anti-PD-1 antibodies, maximum direct and
functional receptor occupancy was observed with both CD3+ binding and IL-2
stimulation assays at all three dose levels evaluated. In Part 2A (n=13), full
receptor occupancy, as assessed by the assays used in Part 1, was maintained
over 3 and 6 weeks at doses of 500 mg and 1,000 mg, respectively.
These preliminary findings indicate that TSR-042 is safe and well tolerated,
with a safety and efficacy profile expected for an agent targeting the PD-1
pathway, evidence of linear PK, and sustained target engagement at
administration intervals up to 6 weeks. The recommended Phase 2 dose was
established at 500 mg Q3W for the first four cycles and 1000 mg Q6W thereafter.
Serum concentrations of TSR-042 observed 3 weeks after the 500 mg dose were
comparable to those observed 6 weeks after the 1000 mg dose. Patients with
microsatellite instability high (MSI-H) and microsatellite stable endometrial
cancer and non-small cell lung cancer are currently enrolling in the expansion
phase of this study, and additional tumor types are planned for evaluation.
About ZEJULA(®) (Niraparib)
Niraparib is marketed in the United States under trade name ZEJULA(®). ZEJULA
(niraparib) is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated 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.
ZEJULA (niraparib) Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in
patients treated with ZEJULA in all clinical studies. Discontinue ZEJULA if
MDS/AML is confirmed.
Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have
been reported in patients treated with ZEJULA. Do not start ZEJULA until
patients have recovered from hematological toxicity caused by previous
chemotherapy (less than or equal to Grade 1). Monitor complete blood counts
weekly for the first month, monthly for the next 11 months of treatment, and
periodically after this time.
Hypertension and hypertensive crisis have been reported in patients treated with
ZEJULA. Monitor blood pressure and heart rate monthly for the first year and
periodically thereafter during treatment with ZEJULA. Closely monitor patients
with cardiovascular disorders, especially coronary insufficiency, cardiac
arrhythmias, and hypertension.
Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females
of reproductive potential of the potential risk to a fetus and to use effective
contraception during treatment and for six months after receiving the final
dose. Because of the potential for serious adverse reactions in breastfed
infants from ZEJULA, advise a lactating woman not to breastfeed during treatment
with ZEJULA and for one month after receiving the final dose.
In clinical studies, the most common adverse reactions included:
thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, abdominal
pain/distension, mucositis/stomatitis, diarrhea, fatigue/asthenia, decreased
appetite, headache, insomnia, nasopharyngitis, dyspnea, rash and hypertension.
Please see full Prescribing Information for additional Safety Information
at www.zejula.com.
About TSR-042
TSR-042 is a monoclonal antibody targeting PD-1 and 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.
About TESARO
TESARO is an oncology-focused biopharmaceutical company devoted to providing
transformative therapies to people bravely facing cancer. For more information,
visit www.tesarobio.com, and follow us on Twitter and LinkedIn.
Investor/Media Contact:
Jennifer Davis
Vice President, Corporate Communications & Investor Relations
+1.781.325.1116 or jdavis(at)tesarobio.com
This announcement is distributed by Nasdaq Corporate Solutions on behalf of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.
Source: TESARO, Inc. via GlobeNewswire
Unternehmensinformation / Kurzprofil:
Datum: 11.09.2017 - 14:00 Uhr
Sprache: Deutsch
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