- 25/26 (96%) Responding Patients Remain on
Therapy, With Median Follow-Up of 9.5 Months -
Loxo Oncology, Inc. (Nasdaq: LOXO), a biopharmaceutical company
developing highly selective medicines for patients with genomically
defined cancers, today announced updated interim clinical data for
LOXO-292 from the global Phase 1/2 LIBRETTO-001 trial in patients
with RET fusion-positive non-small cell lung cancer (NSCLC) who
were initially included in the LOXO-292 presentation at the 2018
ASCO Annual Meeting. In these 38 patients, approximately 3.5 months
of additional patient follow-up were available, as were first
follow-up scans for the eight patients most recently enrolled.
Twenty-five of 26 (96%) responding patients remained on therapy,
with median follow-up of 9.5 months. Inclusion of new restaging
data for the most recently enrolled patients resulted in a 68%
confirmed overall response rate in the presented subset. These data
are being presented today at the 2018 IASLC 19th World Conference
on Lung Cancer in Toronto (abstract 13922).
“I am pleased that the attendees of World Lung were
able to see the activity of LOXO-292 in RET fusion-positive lung
cancer,” said Geoffrey R. Oxnard, M.D., associate professor of
medicine at Harvard Medical School and thoracic oncologist at
Dana-Farber Cancer Institute. “It has been just a few months since
ASCO, but the additional follow-up afforded by today’s data provide
encouraging evidence that LOXO-292 can deliver durable responses in
heavily pre-treated patients. It was additionally reassuring to see
that that LOXO-292 appears to be well tolerated at the Phase 2 dose
of 160 mg BID. With Breakthrough Therapy Designation in hand,
LOXO-292 is moving rapidly through clinical development, so it is
important for investigators and patients to pay attention to this
emerging target and class of medicines.”
Trial Background
LIBRETTO-001 is a Phase 1/2 trial of LOXO-292 in
advanced cancer patients who primarily have activating RET
alterations. LIBRETTO-001 contains a Phase 1 dose escalation phase
and a Phase 2 dose expansion phase. The primary endpoint of the
Phase 1 is the determination of the maximum tolerated dose (MTD) or
recommended dose for further study. Secondary endpoints include
safety, overall response rate (by RECIST 1.1) and duration of
response. Initial clinical data were first reported at the 2018
American Society of Clinical Oncology (ASCO) Annual Meeting.
Key Data Presented
The data presented today were based on a July 19,
2018 data cut-off date and included the 38 patients with RET
fusion-positive NSCLC who were initially included in the LOXO-292
presentation at the 2018 ASCO Annual Meeting.
Patients were heavily pretreated, having received a
median of three prior systemic treatment regimens. Thirty-nine
percent had received both prior platinum-based chemotherapy and an
anti-PD-1 or anti-PD-L1 therapy.
With 3.5 months of additional follow-up since the
2018 ASCO Annual Meeting presentation, LOXO-292 demonstrated
encouraging, early evidence of durable activity, with 25 of 26
(96%) responding RET fusion-positive NSCLC patients remaining on
therapy and 24 of 26 (92%) remaining in response (median follow-up
of 8.5 months for all 38 patients; median follow-up of 9.5 months
for responding patients). The longest responding patient on therapy
was the first RET fusion-positive NSCLC patient enrolled, who had
been on therapy for more than 14 months as of the data cut-off
date.
The new data cutoff date allowed for the inclusion
of first follow-up scans for eight patients who had not had any
post-baseline response assessment as of the ASCO presentation. Of
38 patients with RET fusion-positive NSCLC, 26 demonstrated an
objective response by RECIST 1.1 (all partial responses, including
one patient with an unconfirmed partial response awaiting a
confirmatory response assessment) and six additional patients
demonstrated evidence of tumor regression (-3% to -29%). The
overall response rate was 68% (26/38) (95% CI: 51%-83%) and the
confirmed overall response rate was 68% (25/37) (95% CI: 50%-82%).
Response assessments were performed by the local clinical trial
sites.
Anti-tumor activity was observed regardless of RET
fusion partner (including KIF5B) and prior treatment, including
chemotherapy, immunotherapy and multikinase inhibitors. Four
patients had RECIST target lesions in the central nervous system
(CNS) and all four exhibited confirmed intracranial responses by
RECIST 1.1 (one complete response, three partial responses).
Of the 82 patients in the safety analysis, most
treatment-emergent adverse events were Grade 1 in severity and
judged by the investigator as not related to LOXO-292. The
treatment-emergent adverse events observed in ≥10% of patients,
regardless of relationship to LOXO-292, were diarrhea (15% Grade 1,
7% Grade 2, 1% Grade 3), fatigue (9% Grade 1, 13% Grade 2, 0%
≥Grade 3), dry mouth (21% Grade 1, 0% ≥Grade 2), constipation (17%
Grade 1, 2% Grade 2, 0% ≥Grade 3), hypomagnesemia (12% Grade 1, 1%
Grade 2, 0% ≥Grade 3), cough (11% Grade 1, 1% Grade 2, 0% ≥Grade
3), headache (10% Grade 1, 1% Grade 2, 1% Grade 3) and nausea (9%
Grade 1, 4% Grade 2, 0% ≥Grade 3). Four patients experienced
adverse events ≥Grade 3 that were attributed to LOXO-292 (all Grade
3): tumor lysis syndrome, increased ALT/AST, diarrhea, and
thrombocytopenia. All resolved with dose interruption. 160mg BID
has been advanced as the Phase 2 dose, with dose exploration at
200mg BID ongoing to further characterize LOXO-292 safety and
efficacy.
The presentation will be available online at
https://ir.loxooncology.com/events-presentations.
About LOXO-292LOXO-292 is an oral
and selective investigational new drug in clinical development for
the treatment of patients with cancers that harbor abnormalities in
the rearranged during transfection (RET) kinase. RET fusions and
mutations occur across multiple tumor types with varying frequency.
LOXO-292 was designed to inhibit native RET signaling as well as
anticipated acquired resistance mechanisms that could otherwise
limit the activity of this therapeutic approach. LOXO-292 has been
granted Breakthrough Therapy Designation by the U.S. FDA.
LOXO-292 is currently being studied in
the global LIBRETTO-001 Phase 1/2 trial. For additional
information about the LOXO-292 clinical trial, please refer
to www.clinicaltrials.gov. Interested patients and physicians
can contact the Loxo Oncology Physician and Patient RET Clinical
Trial Hotline at 1-855-RET-4-292 or
email clinicaltrials@loxooncology.com.
About RET-Altered CancersGenomic
alterations in RET kinase, which include fusions and activating
point mutations, lead to overactive RET signaling and uncontrolled
cell growth. RET fusions have been identified in approximately 2%
of non-small cell lung cancer, 10-20% of papillary and other
thyroid cancers, and a subset of other cancers. Activating RET
point mutations account for approximately 60% of medullary thyroid
cancer (MTC). Both RET fusion cancers and RET-mutant MTC are
primarily dependent on this single activated kinase for their
proliferation and survival. This dependency, often referred to as
“oncogene addiction,” renders such tumors highly susceptible to
small molecule inhibitors targeting RET.
About Loxo OncologyLoxo
Oncology is a biopharmaceutical company developing highly selective
medicines for patients with genomically defined cancers. Our
pipeline focuses on cancers that are uniquely dependent on single
gene abnormalities, such that a single drug has the potential to
treat the cancer with dramatic effect. We believe that the most
selective, purpose-built medicines have the highest probability of
maximally inhibiting the intended target, with the intention of
delivering best-in-class disease control and safety. Our management
team seeks out experienced industry partners, world-class
scientific advisors and innovative clinical-regulatory approaches
to deliver new cancer therapies to patients as quickly and
efficiently as possible. For more information, please visit the
company's website at www.loxooncology.com.
Forward Looking StatementsThis
press release contains "forward-looking" statements within the
meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. Forward-looking
statements can be identified by words such as: "anticipate,"
"intend," "plan," "goal," "seek," "believe," "project," "estimate,"
"expect," "strategy," "future," "likely," "may," "should," "will"
and similar references to future periods. These statements are
subject to numerous risks and uncertainties that could cause actual
results to differ materially from what we expect. Examples of
forward-looking statements include, among others, statements we
make regarding the timing and success of our clinical trials, the
potential therapeutic benefits and economic value of LOXO-292 or
other product candidates, and timing of future filings. Further
information on potential risk factors that could affect our
business and its financial results are detailed in our most recent
Quarterly Report on Form 10-Q, and other reports as filed from time
to time with the Securities and Exchange Commission. We undertake
no obligation to publicly update any forward-looking statement,
whether written or oral, that may be made from time to time,
whether as a result of new information, future developments or
otherwise.
Contacts for Loxo Oncology,
Inc.
Company: Lauren CohenDirector, Corporate
Communicationslcohen@loxooncology.com
Investors:Peter Rahmer Endurance Advisors, LLC
415-515-9763 prahmer@enduranceadvisors.com
Media:Dan Budwick1AB
Media973-271-6085dan@1abmedia.com
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