- 16/17 (94%) Responding RET-Mutant Medullary
Thyroid Cancer Patients Remain on Therapy, With Median Follow-Up of
8.4 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-mutant medullary thyroid cancer (MTC) and RET
fusion-positive thyroid cancer 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 nine patients
most recently enrolled. Sixteen of 17 (94%) responding RET-mutant
MTC patients remained on therapy, with median follow-up of 8.4
months. Seven of seven (100%) responding RET fusion-positive
thyroid cancer patients remained on therapy, with median follow-up
of 8.5 months. Inclusion of new restaging data for the most
recently enrolled patients resulted in a 59% overall response rate
(56% confirmed overall response rate) in the presented subset of
RET-mutant MTC patients, and a 78% confirmed overall response rate
in the presented subset of RET fusion-positive thyroid cancer
patients. These data are being presented today at the 88th Annual
Meeting of the American Thyroid Association.
“I am very pleased to present the latest LOXO-292 clinical data
to colleagues at ATA, demonstrating the activity and safety profile
of this promising new agent for RET-altered thyroid cancers,” said
Lori J. Wirth, M.D., associate professor of medicine at Harvard
Medical School and Massachusetts General Hospital. “In the months
since ASCO we continue to see encouraging early evidence that
LOXO-292 has the potential to provide durable responses in heavily
pre-treated patients with RET-driven cancers, with a promising
safety profile at the Phase 2 dose of 160 mg BID. RET has been a
known oncogene in thyroid cancer for many years and I am hopeful
that these LOXO-292 data can further increase the awareness of this
important target and, with Breakthrough Therapy Designation in
hand, that the clinical program will quickly advance to reach our
patients in need. "
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 29 patients with RET-mutant MTC and
the nine patients with RET fusion-positive thyroid cancer 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. Of the patients with
RET-mutant MTC, 79% had previously received cabozantinib or
vandetanib and 45% had received prior treatment with both agents.
Of the patients with RET fusion-positive thyroid cancer, 78% had
previously received radioactive iodine and 78% had previously
received sorafenib or lenvatinib.
With 3.5 months of additional follow-up since the 2018 ASCO
Annual Meeting presentation, LOXO-292 demonstrated encouraging,
early evidence of durable activity. Sixteen of 17 (94%) responding
RET-mutant MTC patients remained on therapy and in response (median
follow-up of 7.6 months for all 29 patients; median follow-up of
8.4 months for responding patients). Seven of seven (100%)
responding RET fusion-positive thyroid remained on therapy and in
response (median follow-up of 7.6 months for all nine patients;
median follow-up of 8.5 months for responding patients). The
longest treated patient was the first RET-mutant MTC patient
enrolled, who had been on therapy for more than 13 months as of the
data cut-off date.
The new data cutoff date allowed for the inclusion of first
follow-up scans for nine patients (seven with RET-mutant MTC and
two with RET fusion-positive thyroid cancer) who had not had any
post-baseline response assessment as of the ASCO presentation. Of
29 patients with RET-mutant MTC, 17 demonstrated an objective
response by RECIST 1.1 (two complete responses and 15 partial
responses, including two patients with unconfirmed partial
responses awaiting confirmatory response assessments) and seven
additional patients demonstrated evidence of tumor regression (-12%
to -26%). The overall response rate was 59% (17/29) (95% CI:
39%-77%) and the confirmed overall response rate was 56% (15/27)
(95% CI: 35%-75%). Included in this analysis are two patients with
non-measurable disease at baseline (1 confirmed complete response,
1 stable disease). Of nine patients with RET fusion-positive
thyroid cancer, seven demonstrated an objective response by RECIST
1.1 (all partial responses) and one additional patient demonstrated
evidence of tumor regression (-21%). The confirmed overall response
rate was 78% (7/9) (95% CI: 40%-97%). Included in the analysis is
one patient with non-measurable disease at baseline (stable
disease). Response assessments were performed by the local clinical
trial sites.
Anti-tumor activity was observed regardless of RET mutation, RET
fusion partner, and prior multikinase inhibitor treatment. One
patient, with RET fusion-positive thyroid cancer, had RECIST target
lesions in the central nervous system (CNS) and exhibited an
intracranial partial response by RECIST 1.1, pending
confirmation.
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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