WHIPPANY, N.J., Oct. 21, 2018 /PRNewswire/ -- Bayer and Loxo
Oncology, Inc. (Nasdaq: LOXO), today announced updated clinical
data for larotrectinib in adult and pediatric patients with TRK
fusion cancer across 24 unique tumor types. The update included
approximately one year of additional follow-up for a primary
dataset of 55 patients as well as results from a supplementary
dataset of 67 patients.1 The overall response rates
(ORR) in these groups were 80 percent and 81 percent, respectively,
while the median duration of response (mDOR) had not yet been
reached in either group.1 Complete responses (CR) in the
primary dataset continued to mature, increasing to 18 percent,
while the additional patients in the supplementary dataset
experienced a CR rate of 17 percent.1 These data are
being presented today at the ESMO 2018 Congress (European Society
for Medical Oncology).
This is the only analysis to examine the efficacy and safety of
a single-purpose drug for the treatment of TRK fusion cancer. The
122-patient integrated dataset (109 patients included in the
efficacy analysis) included both adult and pediatric patients with
TRK fusion cancer across 24 unique tumor types, ranging in age from
approximately one month to 80 years.1 Tumor types
included 10 distinct soft tissue sarcomas, salivary gland,
infantile fibrosarcoma, thyroid, lung, melanoma, colon,
gastrointestinal stromal tumor, breast, bone sarcoma,
cholangiocarcinoma, carcinoma of unknown primary, congenital
mesoblastic nephroma, appendiceal, and pancreas
cancers.1 Safety results were generally consistent with
previous presentations, with the majority of adverse events (AE)
grade 1 or 2.1 No treatment-related grade 3 or 4 AEs
occurred in more than 5 percent of patients.1
"It is exciting to see larotrectinib deliver responses to
patients in these studies with TRK fusion cancer, across different
ages, tumor sites of origin, or CNS involvement," said Ulrik Lassen, M.D., Ph.D., Department of
Oncology, Rigshospitalet, Copenhagen. "In the supplementary set, the
response rate is nearly the same as in the primary set and duration
of response has actually increased with longer patient follow-up.
The larotrectinib experience provides strong clinical evidence
supporting the development of single-purpose drugs against
oncogenic driver targets, and underscores the importance of tumor
genomic profiling capable of identifying NTRK gene fusions
alongside other activating alterations."
"These data from a large patient group with TRK fusion cancer
are truly encouraging – bringing us one step further to delivering
this treatment to patients," said Dr. Scott
Z. Fields, Senior Vice President and Head of Oncology
Development at Bayer's Pharmaceutical Division. "We look forward to
bringing this potential treatment option to adults and children
with TRK fusion cancer as soon as possible."
The U.S. Food and Drug Administration (FDA) granted Priority
Review for larotrectinib for the treatment of adult and pediatric
patients with locally advanced or metastatic solid tumors harboring
a neurotrophic tyrosine receptor kinase (NTRK) gene fusion.
The FDA has set a target action date of November 26, 2018, under the Prescription Drug
User Fee Act (PDUFA). Bayer has submitted a Marketing Authorization
Application (MAA) in the European Union (EU) and additional filings
in other markets are underway.
Detailed Results Presented at ESMO 2018 Congress
The
ESMO 2018 Congress presentation included additional follow-up for
the first 55 consecutively enrolled adult and pediatric patients
with TRK fusion cancer treated across the Phase I adult trial,
Phase II trial (NAVIGATE), and Phase I/II pediatric trial
(SCOUT).1 These patients were the subject of the New
England Journal of Medicine publication and constitute the
primary analysis population supporting larotrectinib's NDA filing.
The presentation also included data for the 67 TRK fusion cancer
patients subsequently enrolled.1 Presented data were
based on a July 30, 2018 data cut-off
date, providing approximately one year of additional follow-up for
the primary analysis population.1
The datasets included patients with RECIST-evaluable disease
enrolled to the three clinical trials, regardless of prior therapy
or testing methodology used to establish their TRK fusion
status.1 In the ESMO 2018 Congress presentation,
response evaluations were based on investigator
assessment.1
In the primary dataset, the overall response rate (ORR) was 80
percent (44/55) (95% CI: 67-90%), with a 62 percent partial
response (PR) rate and an 18 percent complete response (CR)
rate.1 In the supplementary dataset, the ORR was 81
percent (44/54) (95% CI: 69-91%), with a 65 percent PR rate and a
17 percent CR rate.1 Across both datasets, the ORR was
81 percent (88/109) (95% CI: 72-88%), with a 63 percent PR rate and
a 17 percent CR rate.1 The ORR analyses for the
supplementary and integrated datasets included nine patients with
unconfirmed PRs awaiting confirmatory response assessments; they
did not include 13 patients who were awaiting an initial response
assessment and continuing on study.1
Median duration of response (mDOR) had not been reached in
either the primary dataset or supplementary dataset, with median
follow-up of 17.6 months and 7.4 months, respectively.1
In the primary dataset, Kaplan-Meier landmark analyses improved
since the July 2017 data cut-off
date.1 At six months, 88 percent of responses were
ongoing (83 percent based on the July
2017 data cut-off date). At 12 months, 75 percent of
responses were ongoing (71 percent based on the July 2017 data cut-off date). Kaplan-Meier
landmark analyses of the supplementary dataset were highly
concordant with the primary dataset.1 At six months, 93
percent of responses were ongoing and at 12 months, 81 percent of
responses were ongoing.1 Across the integrated dataset,
as of the July 2018 data cut-off
date, 84 percent of responding patients remained on treatment or
had undergone surgery with curative intent.1
The safety data presented at the ESMO 2018 Congress encompassed
the entire larotrectinib safety database in cancer patients
(n=207). The majority of adverse events (AE) reported were grade 1
or 2.1 No treatment-related grade 3 or 4 AEs occurred in
more than 5 percent of patients.1 Of the 122 patients
with TRK fusion cancer, 11 patients (9 percent) required
larotrectinib dose reductions.1 In all cases, patients
whose doses were reduced maintained their best response at the
lower dose.1 One patient (<1 percent) discontinued
larotrectinib due to an AE.1
About Larotrectinib
Larotrectinib is an
investigational tropomyosin receptor kinase (TRK) inhibitor in
clinical development for the treatment of patients with solid
tumors that harbor a neurotrophic tyrosine receptor kinase
(NTRK) gene fusion. Growing research suggests that the
NTRK genes can become abnormally fused to other genes,
producing a TRK fusion protein that can lead to the development of
solid tumors across various sites of the body.2-4
In November 2017, Bayer and Loxo
Oncology entered into an exclusive global collaboration for the
development and commercialization of larotrectinib and LOXO-195, a
TRK inhibitor in clinical development. Bayer and Loxo Oncology will
jointly develop the two products with Loxo Oncology leading the
ongoing clinical studies as well as the filing in the U.S., and
Bayer leading ex-U.S. regulatory activities and worldwide
commercial activities. In the U.S., Bayer and Loxo Oncology will
co-promote the products.
For additional information about the larotrectinib clinical
trials, please refer to www.clinicaltrials.gov or visit
www.loxooncologytrials.com. Larotrectinib has not been approved by
the U.S. Food and Drug Administration, the European Medicines
Agency or any other health authority.
About TRK Fusion Cancer
TRK fusion cancer occurs when
a neurotrophic tyrosine receptor kinase (NTRK) gene fuses
with another unrelated gene, producing an altered tropomyosin
receptor kinase (TRK) protein.2,3,5 The altered protein,
or TRK fusion protein, becomes constitutively active or
overexpressed, and triggers a signaling cascade.2 These
proteins become the primary oncogenic driver of the spread and
growth of tumors.4 NTRK gene fusions
have been identified in various adult and pediatric solid tumors
with varying frequencies.4
About Oncology at Bayer
Bayer is committed to
delivering science for a better life by advancing a
portfolio of innovative treatments. The oncology franchise at
Bayer now includes four oncology products and several other
compounds in various stages of clinical development. Together,
these products reflect the company's approach to research, which
prioritizes targets and pathways with the potential to impact the
way that cancer is treated.
About Bayer
Bayer is a global enterprise with core
competencies in the Life Science fields of health care and
agriculture. Its products and services are designed to benefit
people and improve their quality of life. At the same time, the
Group aims to create value through innovation, growth and high
earning power. Bayer is committed to the principles of sustainable
development and to its social and ethical responsibilities as a
corporate citizen. In fiscal 2017, the Group employed around 99,800
people and had sales of EUR 35.0
billion. Capital expenditures amounted to EUR 2.4 billion, R&D expenses to EUR 4.5 billion. For more information, go to
www.bayer.us.
© 2018 Bayer
BAYER® and the Bayer Cross are registered trademarks of
Bayer.
Media Contact:
Rose
Talarico, Tel. +1 862.404.5302
E-Mail: rose.talarico@bayer.com
Forward-Looking Statement
This news release may
contain forward-looking statements based on current assumptions and
forecasts made by Bayer Group or subgroup management. Various known
and unknown risks, uncertainties and other factors could lead to
material differences between the actual future results, financial
situation, development or performance of the company and the
estimates given here. These factors include those discussed in
Bayer's public reports which are available on the Bayer website at
www.bayer.com. The company assumes no liability whatsoever to
update these forward-looking statements or to conform them to
future events or developments.
References
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1.
|
Lassen, Ulrik,
Albert, Catherine, Kummar, Shivaani, et al. Larotrectinib efficacy
and safety in TRK fusion cancer: an expanded clinical dataset
showing consistency in an age and tumor agnostic approach. In:
Proceedings from the European Society for Medical Oncology 2018
Congress; October 21, 2018; Munich, Germany. Abstract
409O.
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Amatu A,
Sartore-Bianchi A, Siena S. ESMO Open.
2016;1(2):e000023.
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Vaishnavi A, Le AT,
Doebele RC. Cancer Discov. 2015;5(1):25-34.
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4.
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Stransky N, Cerami E,
Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in
cancer. Nat Commun. 2014;5:4846.
doi:10.1038/ncomms5846.
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Kumar-Sinha C,
Kalyana-Sundaram S, Chinnaiyan AM. Landscape of gene fusions in
epithelial cancers: seq and ye shall find. Genome Med.
2015;7:129. doi:10.1186/s13073-015-0252-1.
|
Abstract: 409O
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