Updated preliminary data to be presented at
the 35th AACR-NCI-EORTC Symposium
Company plans to host a conference call on
October 13, 2023 at 8:00am EDT
CAMBRIDGE, Mass., Oct. 4, 2023
/PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage
biopharmaceutical company focused on
creating precisely targeted therapies for
clinically proven kinase targets in cancer, today announced
preliminary data from the Phase 1 dose-escalation portion of its
ongoing ALKOVE-1 Phase 1/2 clinical trial of NVL-655 for patients
with advanced ALK-positive non-small cell lung cancer (NSCLC) and
other solid tumors as reported in an abstract accepted for
presentation at the 35th AACR-NCI-EORTC (ANE) Symposium in
Boston, Massachusetts. Updated
preliminary data will be presented at the conference and during a
live webcast and conference call with management on October 13th at 8:00am EDT.
NVL-655 is a novel brain-penetrant ALK-selective tyrosine kinase
inhibitor (TKI) created with the aim to simultaneously overcome the
clinical challenges of emergent treatment resistance, brain
metastases, and off-target central nervous system (CNS) adverse
events associated with tropomyosin receptor kinase (TRK) inhibition
that may limit the use of currently available ALK TKIs.
NVL-655 is currently being evaluated in the ALKOVE-1 Phase 1/2
clinical trial, a first-in-human study of NVL-655 in patients with
advanced ALK-positive NSCLC and other solid tumors (NCT05384626).
The Phase 1 dose escalation portion is enrolling ALK-positive NSCLC
patients who have previously received at least one ALK TKI and
patients with other ALK-positive solid tumors who have been
previously treated with at least one prior systemic anticancer
therapy. The primary objectives are to determine the recommended
Phase 2 dose (RP2D) and if applicable, the maximum tolerated dose
(MTD) of NVL-655 in patients with ALK-positive solid tumors.
Additional objectives include characterization of the overall
safety, tolerability, and pharmacokinetic profile, and evaluation
of the preliminary anti-tumor activity of NVL-655.
As of June 12, 2023, 57 patients
(54 NSCLC, 3 other solid tumors) received NVL-655 orally at dose
levels ranging from 15 to 200 mg once daily in the Phase 1 dose
escalation portion of ALKOVE-1.
The patient population was heavily pre-treated and included:
- patients with baseline CNS metastases (51%);
- patients with ALK resistance mutations (47%), including
compound ALK mutations (32%);
- patients who had received ≥3 prior ALK TKIs (53%); and,
- patients who had received ≥1 2nd generation ALK
TKI (alectinib, brigatinib, ceritinib) and the 3rd
generation ALK TKI lorlatinib (77%).
Preliminary activity of NVL-655 was demonstrated in this heavily
pre-treated patient population as measured by objective response
rate (ORR) per RECIST 1.1. Partial responses were observed in 45%
(15/33; 8 pending confirmation) of response-evaluable patients with
ALK-positive NSCLC who received NVL-655 at doses ranging from
15-150 mg once daily. An ORR of 65% (11/17) was observed in
patients with baseline ALK resistance mutations, and an ORR of 41%
(12/29) was observed in patients post-lorlatinib, including cases
with compound resistance mutations. Early indicators of CNS
activity were also observed.
Preliminary pharmacokinetic analysis demonstrated
dose-proportional exposure, and preliminary pharmacodynamic
analysis showed reductions, including clearance, of ALK fusion and
mutation variants in ctDNA.
NVL-655 was well-tolerated and treatment-related adverse events
(TRAEs) were generally mild. The most frequent TRAEs were nausea
(12%), transaminase elevation (12%), fatigue (9%), and constipation
(7%). Grade ≥3 TRAEs were transaminase elevation (n=2), CPK
elevation (n=1), and fatigue (n=1). An MTD was not identified and
Phase 1 was ongoing to determine the RP2D.
"We are strongly encouraged by these preliminary safety and
clinical activity data from the Phase 1 portion of our ALKOVE-1
clinical trial, which demonstrate the potential for NVL-655 to
achieve its target product profile of potent and selective
targeting of ALK fusions and secondary ALK single and compound
resistance mutations, brain penetrance, and the avoidance of TRK
inhibition," said Christopher
Turner, M.D., Chief Medical Officer of Nuvalent. "We look
forward to presenting an update to this data at the AACR-NCI-EORTC
Symposium later this month."
Details for the presentation are as follows:
Title: Safety and preliminary activity of the selective
ALK inhibitor NVL-655 in patients with ALK fusion-positive solid
tumors
Abstract Number: 35177
Poster Number: B154
Session: Poster Session B
Session Date and Time: Friday,
October 13, 12:30 pm-4:00 pm
EDT
Presenting Author: Jessica J Lin, Massachusetts General
Hospital (MGH), Boston, MA
Webcast and Conference Call Information
A conference call with management will be held on October 13th at 8:00 am EDT. To access the call, please
dial +1 (866) 652-5200 (domestic) or +1 (412) 317-6060
(international) at least 10 minutes prior to the start time and ask
to be joined to the Nuvalent call. Accompanying slides and a live
video webcast will be available in the Investors section of the
Nuvalent website at https://investors.nuvalent.com/events. A replay
and accompanying slides will be archived on the Nuvalent website
for 30 days.
About NVL-655
NVL-655 is a novel brain-penetrant ALK-selective inhibitor
created with the aim to overcome limitations observed with
currently available ALK inhibitors. NVL-655 is designed to remain
active in tumors that have developed resistance to first-, second-,
and third-generation ALK inhibitors, including tumors with the
solvent front G1202R mutation or compound mutations G1202R / L1196M
("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF").
NVL-655 has been designed for CNS penetrance to improve treatment
options for patients with brain metastases. NVL-655 has been
observed in preclinical studies to selectively inhibit wild-type
ALK and its resistance variants over the structurally related
tropomyosin receptor kinase (TRK) family to potentially avoid
TRK-related CNS adverse events seen with dual TRK/ALK inhibitors
and drive more durable responses for patients. NVL-655 is currently
being investigated in the ALKOVE-1 clinical trial (NCT05384626), a
first-in-human Phase 1/2 clinical trial for patients with advanced
ALK-positive non-small cell lung cancer (NSCLC) and other solid
tumors.
About Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage
biopharmaceutical company focused on
creating precisely targeted therapies for patients
with cancer, designed to overcome the limitations of existing
therapies for clinically proven kinase targets. Leveraging deep
expertise in chemistry and structure-based drug design, we develop
innovative small molecules that have the potential to overcome
resistance, minimize adverse events, address brain metastases, and
drive more durable responses. Nuvalent is advancing a robust
pipeline with parallel lead programs in ROS1-positive and
ALK-positive non-small cell lung cancer (NSCLC), a program in HER2
Exon 20 Insertion positive cancers, and multiple discovery-stage
research programs. We routinely post information that may be
important to investors on our website
at www.nuvalent.com. Follow us on Twitter (@nuvalent)
and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, implied and
express statements regarding Nuvalent's strategy, business plans,
and focus; the expected timing of data announcements; the
preclinical and clinical development programs for NVL-655; the
potential clinical effect of NVL-655; the design and enrollment of
the ALKOVE-1 clinical trial; the potential of NVL-655; Nuvalent's
research and development programs for the treatment of cancer; and
risks and uncertainties associated with drug development. The words
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"plan," "anticipate," "aim," "goal," "intend," "believe," "expect,"
"estimate," "seek," "predict," "future," "project," "potential,"
"continue," "target" or the negative of these terms and similar
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involve a high degree of risk, and only a small number of research
and development programs result in commercialization of a product.
You should not place undue reliance on these statements or the
scientific data presented.
Any forward-looking statements in this press release are based
on management's current expectations and beliefs and are subject to
a number of risks, uncertainties, and important factors that may
cause actual events or results to differ materially from those
expressed or implied by any forward-looking statements contained in
this press release, including, without limitation: risks that
Nuvalent may not fully enroll the ALKOVE-1 clinical trial or that
enrollment will take longer than expected; unexpected concerns that
may arise from additional data, analysis, or results obtained
during preclinical studies or clinical trials, including ALKOVE-1;
the occurrence of adverse safety events; risks of unexpected costs,
delays, or other unexpected hurdles; risks that Nuvalent may not be
able to nominate drug candidates from its discovery programs; the
direct or indirect impact of public health emergencies or global
geopolitical circumstances on the timing and anticipated timing and
results of Nuvalent's clinical trials, strategy, and future
operations, including the ALKOVE-1 clinical trial; the timing and
outcome of Nuvalent's planned interactions with regulatory
authorities; and risks related to obtaining, maintaining, and
protecting Nuvalent's intellectual property. These and other risks
and uncertainties are described in greater detail in the section
entitled "Risk Factors" in the Company's Quarterly Report on Form
10-Q for the quarterly period ended June 30,
2023, as well as any prior and subsequent filings with the
Securities and Exchange Commission. In addition, any
forward-looking statements represent Nuvalent's views only as of
today and should not be relied upon as representing its views as of
any subsequent date. Nuvalent explicitly disclaims any obligation
to update any forward-looking statements.
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