Turning Point Therapeutics Announces Initial Clinical Data From Phase 1/2 SWORD-1 Study of RET Inhibitor TPX-0046
06 April 2021 - 6:01AM
Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision
oncology company developing next-generation therapies that target
genetic drivers of cancer, today reported initial clinical data
from the ongoing Phase 1/2 SWORD-1 study of its RET inhibitor drug
candidate, TPX-0046.
The initial data from the Phase 1 dose finding portion of the
study showed preliminary clinical activity, including objective
responses and a generally well-tolerated safety profile. Turning
Point continues to evaluate doses and schedules to determine a
recommended Phase 2 dose, and plans to revise the study protocol to
include Phase 1 expansion cohorts at the recommended Phase 2 dose.
“RET-driven cancers affect nearly 10,000 patients
annually in the U.S. and E.U., and patients who progress following
treatment with a selective RET inhibitor remain particularly
underserved,” said Alexander Drilon, M.D., chief, Early Drug
Development Service, Memorial Sloan Kettering Cancer Center. “While
we continue to evaluate TPX-0046, the initial preliminary data are
encouraging, with a generally tolerable safety profile and early
signals of activity.”
TPX-0046 Initial Clinical DataTwenty-one
patients enrolled in the study including 10 with non-small cell
lung cancer (NSCLC) and 11 with medullary thyroid carcinoma (MTC)
who were treated from December 2019 to the data cut-off date of
March 10, 2021. Patients included those with RET-altered TKI-naïve
NSCLC (n=3; all previously treated with platinum-based chemotherapy
and immunotherapy) and MTC (n=2), and TKI-pretreated NSCLC (n=7)
and MTC (n=9).
All 16 TKI-pretreated patients were previously treated with a
selective RET TKI and 9 patients (56%) were treated with more than
1 prior TKI. Ninety-one percent of patients (19/21) had a baseline
ECOG performance score of 1, and nearly half (10/21) received 3 or
more prior therapies.
Preliminary efficacy data by investigator assessment was
available for 14 evaluable patients with baseline measurable
disease and at least one post-baseline assessment per RECIST v1.1,
including TKI-naïve NSCLC (n=3) and MTC (n=2), and TKI-pretreated
NSCLC (n=4) and MTC (n=5).
As of the March 10, 2021 data cut-off date:
Preliminary Safety and Pharmacokinetic Results
- A total of 21 patients with RET-altered NSCLC or MTC were
treated with TPX-0046 across multiple doses and schedules from 10mg
once daily (QD) to 30mg QD
- TPX-0046 was generally well tolerated, with the most frequent
treatment emergent adverse event (TEAE) being Grade 1 or 2
dizziness
- The maximum tolerated dose had not been determined, with 1
dose-limiting toxicity of treatment-related Grade 2 gait
disturbance at 30 mg QD
- TEAEs reported in greater than 20 percent of patients were
dizziness (43%); fatigue (38%); alkaline phosphatase increase,
constipation, decreased appetite, dry mouth, hyperphosphataemia,
lipase increase (29% each); and alanine aminotransferase increase,
dehydration, and muscular weakness (24% each)
- There were infrequent dose reductions or drug discontinuations
due to TEAEs
- The majority of treatment related adverse events (TRAEs) were
Grade 1 or 2 and there were no Grade 4 or 5 TRAEs
- There were no treatment related Grade 3 or greater ALT/AST
elevations, any grade of hypertension, hemorrhagic events or QT
prolongation, and no interstitial lung disease or pneumonitis
- Preliminary pharmacokinetic data indicates exposure increases
in a dose dependent manner
Preliminary Efficacy Results
- Of 5 RET TKI-naïve patients, 4 showed tumor regressions of
-42%, -37%, -23%, and -3%, including 2 patients dosed at 30 mg QD
who achieved confirmed partial responses with duration of responses
of 5.6 and 5.8+ months, respectively. Three of the 4 patients with
regressions remained on treatment awaiting their next scan
- Of 9 TKI-pretreated patients, 3 patients (2 treated with only 1
prior selective RET TKI) achieved tumor regressions of -44%, -27%
and -17%. All 3 patients remained on treatment awaiting their next
scan
- Of the 14 evaluable patients, 7 (50%) remained on treatment
with duration of treatment ranging from 5.1 to 51+ weeks
“Given the encouraging data we have seen, we plan to modify the
SWORD-1 study to include a dose expansion portion utilizing
additional clinical sites,” said Mohammad Hirmand, M.D., executive
vice president and chief medical officer of Turning Point
Therapeutics. “We look forward to advancing our development of
TPX-0046 in both the RET-positive TKI-naïve and less heavily
pretreated TKI-pretreated settings.”
After determination of the recommended Phase 2 dose, Turning
Point plans to study TPX-0046 in multiple Phase 1 dose expansion
cohorts in up to 75 patients with RET-altered malignancies prior to
an end of Phase 1 meeting with the Food and Drug
Administration.
Webcast and Conference CallTurning Point will
host a webcast and conference call accompanied by a slide
presentation to discuss the results at 4:30 p.m. ET today. Athena
Countouriotis, M.D., president and chief executive officer, will
host the call, which will also include Dr. Hirmand.
The discussion will be accessible through the "Investors"
section of tptherapeutics.com or by dialing (877) 388-2118 (in the
United States) or (470) 495-9489 (outside the U.S.) using
conference ID 9939858. A replay will be available through the
"Investors" section of www.tptherapeutics.com.
About Turning Point Therapeutics Inc.Turning
Point Therapeutics is a clinical-stage precision oncology
company with a pipeline of internally discovered investigational
drugs designed to address key limitations of existing cancer
therapies. The company’s lead drug candidate, repotrectinib, is a
next-generation kinase inhibitor targeting the ROS1 and TRK
oncogenic drivers of non-small cell lung cancer and advanced solid
tumors. Repotrectinib, which is being studied in a registrational
Phase 2 study in adults and a Phase 1/2 study in pediatric
patients, has shown antitumor activity and durable responses among
kinase inhibitor treatment-naïve and pre-treated patients. The
company’s pipeline of drug candidates also includes TPX-0022,
targeting MET, CSF1R and SRC, which is being studied in a Phase 1
trial of patients with advanced or metastatic solid tumors
harboring genetic alterations in MET; TPX-0046, targeting RET,
which is being studied in a Phase 1/2 trial of patients with
advanced or metastatic solid tumors harboring genetic alterations
in RET; and TPX-0131, a next-generation ALK inhibitor. Turning
Point’s next-generation kinase inhibitors are designed to bind to
their targets with greater precision and affinity than existing
therapies, with a novel, compact structure that has demonstrated an
ability to potentially overcome treatment resistance common with
other kinase inhibitors. The company is driven to develop therapies
that mark a turning point for patients in their cancer treatment.
For more information, visit www.tptherapeutics.com.
Forward Looking StatementsStatements contained
in this press release regarding matters that are not historical
facts are “forward-looking statements” within the meaning of the
Private Securities Litigation Reform Act of 1995. Such
forward-looking statements include statements regarding, among
other things, the efficacy, safety and therapeutic potential of
TPX-0046, the results, conduct, progress and timing of the Phase
1/2 clinical study of TPX-0046, plans regarding future clinical
studies and regulatory discussions, and the regulatory approval
path for TPX-0046. Because such statements are subject to risks and
uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Words such
as “plans”, “will”, “believes,” “anticipates,” “expects,”
“intends,” “goal,” “potential” and similar expressions are intended
to identify forward-looking statements. These forward-looking
statements are based upon Turning Point Therapeutics’ current
expectations and involve assumptions that may never materialize or
may prove to be incorrect. Actual results could differ materially
from those anticipated in such forward-looking statements as a
result of various risks and uncertainties, which include, without
limitation, risks and uncertainties associated with Turning Point
Therapeutics’ business in general, risks and uncertainties related
to the impact of the COVID-19 pandemic to Turning Point’s business
and the other risks described in Turning Point Therapeutics’
filings with the SEC. All forward-looking statements contained in
this press release speak only as of the date on which they were
made. Turning Point Therapeutics undertakes no obligation to update
such statements to reflect events that occur or circumstances that
exist after the date on which they were made.
Contact: Jim
Mazzolajim.mazzola@tptherapeutics.com858-342-8272
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