Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage
biotechnology company discovering and developing tumor-activated
immuno-oncology therapies for people living with cancer, today
announced preliminary data from its Phase 1 clinical trial
evaluating XTX101, an investigational tumor-activated, Fc-enhanced
anti-CTLA-4, in patients with advanced solid tumors.
“We are encouraged by the preliminary data from
the Phase 1 trial for XTX101 showing evidence of tumor-selective
activation,” said Martin Huber, M.D., president and head of
research and development at Xilio. “Following treatment with XTX101
monotherapy at the recommended Phase 2 dose of 150 mg once every
six weeks, we observed a partial response in a patient with PD-L1
negative advanced non-small cell lung cancer. Importantly, this
anti-tumor activity occurred in the absence of meaningful observed
activation of the immune system in the periphery, suggesting
tumor-selective activation of XTX101. Based on these Phase 1 data,
we plan to explore opportunities to evaluate XTX101 in combination
with an anti-PD-(L)1 in historically immunotherapy-resistant tumor
types.”
Data from the Ongoing Phase 1 Clinical
Trial for XTX101
As of a data cutoff date of May 2, 2023, 25
patients had been treated with XTX101, including dose levels
ranging from 7 mg to 180 mg administered once every three weeks
(Q3W) and one dose level at 150 mg administered once every six
weeks (Q6W). Of these patients, 20 patients were dosed in
monotherapy dose-escalation (Part 1A) and five patients were dosed
in monotherapy dose-expansion (Part 1B).
Patients had a wide range of advanced and
treatment-refractory solid tumors, including colorectal cancer
(CRC), non-small cell lung cancer (NSCLC) and pancreatic cancer. In
addition, 76% of patients had been previously treated with at least
three prior lines of anti-cancer therapy, and 44% had been
previously treated with at least one immuno-oncology (I-O) agent.
As of the data cutoff date, three patients were continuing on
treatment with XTX101, and 22 patients had discontinued treatment
with XTX101.
Preliminary Safety Data
A recommended Phase 2 dose (RP2D) and schedule
of 150 mg Q6W was determined based on the favorable preliminary
safety, pharmacokinetic (PK) and pharmacodynamic (PD) data for
XTX101. At the RP2D, no dose-limiting toxicities were observed, and
there was no reported evidence of immune-related endocrine or skin
adverse events (AEs) that are commonly associated with systemically
active anti-CTLA-4 agents. In addition, evidence of effective
masking of XTX101 was demonstrated by low levels of unmasked drug
detected in peripheral circulation, and XTX101 achieved target PK
exposure at the RP2D, reaching the targeted area under the curve
(AUC) and peak concentration (Cmax).
As of the data cutoff date:
- Across all dosing levels and dosing
intervals, no Grade 4 or Grade 5 treatment-related AEs were
reported by investigators.
- Among seven patients who received
XTX101 administered at the RP2D of 150 mg on a Q6W dosing schedule,
the most common treatment-related AEs (≥10% incidence) of any grade
reported by investigators were diarrhea (14%), fatigue (14%) and
decreased appetite (14%). In these patients, no treatment-related
colitis or infusion related reaction of any grade was observed.
Investigators reported only one Grade 3 treatment-related AE of
diarrhea, which occurred after two doses and resolved after five
days without steroid use. This patient tolerated two additional
doses of XTX101 after dose reduction to 75 mg Q6W without any
symptom recurrence. At the RP2D of 150 mg Q6W, this was the only
patient with a dose reduction due to an AE, and no patients
discontinued treatment due to a treatment-related AE.
- Among 18 patients who received
XTX101 administered on a Q3W dosing schedule, the most common
treatment-related AEs (≥10% incidence) of any grade reported by
investigators were diarrhea (28%), colitis (28%), infusion related
reaction (28%), nausea (17%), vomiting (17%) and abdominal pain
(11%). Of these, investigators reported the following Grade 3
treatment-related AEs: diarrhea (6%), colitis (22%) and infusion
related reaction (17%). Infusion related reactions were associated
with antidrug antibodies. Across all dose levels administered Q3W,
two patients had dose reductions due to AEs, and four patients
discontinued treatment due to an infusion related reaction.
Preliminary Anti-Tumor Activity
A partial response was observed at nine weeks in
one patient with advanced PD-L1 negative NSCLC with hepatic
metastases treated with XTX101 at the 150 mg Q6W dose level and
confirmed after the data cutoff date at week 27. The only
treatment-related AE reported for this patient was Grade 1 fatigue.
In addition, PD markers for anti-CTLA-4 reported for this patient
showed minimal immune activation in peripheral circulation,
demonstrating evidence of tumor-selective activation of XTX101. The
patient is currently continuing on treatment with XTX101.
Clinical Development Plan for
XTX101
Enrollment in monotherapy dose-expansion (Part
1B) of the Phase 1 trial is currently ongoing, with the goal of
further characterizing the safety, PK and PD of XTX101 at the RP2D
of 150 mg Q6W. In addition, mandatory tumor biopsies will be
obtained from patients in Part 1B to examine intra-tumoral PK and
PD for XTX101.
Xilio plans to continue to explore strategic
opportunities to advance XTX101 with a partner beyond the current
Phase 1 monotherapy cohorts, including in potential Phase 1 dose
escalation evaluating XTX101 in combination with a PD-(L)1 and in a
potential Phase 2 trial evaluating XTX101 in combination with a
PD-(L)1 in patients with microsatellite stable CRC.
About XTX101 (anti-CTLA-4) and the Phase
1 Clinical Trial
XTX101 is an investigational tumor-activated,
Fc-enhanced anti-CTLA-4 monoclonal antibody designed to deplete
regulatory T cells when activated (unmasked) in the tumor
microenvironment (TME). The Phase 1 clinical trial is a
first-in-human, multi-center, open-label trial designed to evaluate
the safety and tolerability of XTX101 for the treatment of patients
with advanced solid tumors. The primary outcome measures were the
incidence of dose-limiting toxicities (DLTs) and the incidence of
treatment-related adverse events, and changes in clinical
laboratory abnormalities. Please refer to NCT04896697 on
www.clinicaltrials.gov for additional details.
About Xilio Therapeutics
Xilio Therapeutics is a clinical-stage
biotechnology company discovering and developing tumor-activated
immuno-oncology (I-O) therapies with the goal of significantly
improving outcomes for people living with cancer without the
systemic side effects of current I-O treatments. The company is
using its proprietary geographically precise solutions (GPS)
platform to build a pipeline of novel, tumor-activated molecules,
including cytokines and other biologics, which are designed to
optimize their therapeutic index and localize anti-tumor activity
within the tumor microenvironment. Xilio is currently advancing
multiple programs for tumor-activated I-O treatments in clinical
development, as well as programs in preclinical development. Learn
more by visiting www.xiliotx.com and follow us on
Twitter (@xiliotx) and LinkedIn (Xilio Therapeutics,
Inc.).
Cautionary Note Regarding
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,
statements regarding plans, timing and expectations related to: the
ongoing Phase 1 monotherapy dose expansion cohort for XTX101; plans
to continue to explore strategic opportunities to advance XTX101
with a partner beyond the current Phase 1 monotherapy cohorts; the
potential safety and anti-tumor activity of any of Xilio’s current
or future product candidates in treating patients, including
without limitation XTX101; and Xilio’s strategy, goals and
anticipated financial performance, milestones, business plans and
focus. The words “aim,” “may,” “will,” “could,” “would,” “should,”
“expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,”
“predict,” “project,” “potential,” “continue,” “seek,” “target” and
similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. Any forward-looking statements in this
press release are based on management’s current expectations and
beliefs and are subject to a number of important risks,
uncertainties and other 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 and uncertainties related to
the following: ongoing and planned research and development
activities, including initiating, conducting or completing
preclinical studies and clinical trials and the timing and results
of such preclinical studies or clinical trials; the delay of any
current or planned preclinical studies or clinical trials or the
development of Xilio’s current or future product candidates;
Xilio’s ability to obtain and maintain sufficient preclinical and
clinical supply of current or future product candidates; Xilio’s
advancement of multiple early-stage programs; Xilio’s ability to
replicate in future preclinical studies or clinical trials positive
data results from earlier preclinical studies or clinical trials,
such as the preliminary safety and anti-tumor data observed in the
Phase 1 clinical trial for XTX101 as of the data cutoff date;
Xilio’s ability to successfully demonstrate the safety and efficacy
of its product candidates and gain approval of its product
candidates on a timely basis, if at all; the potential for results
from preclinical studies or clinical trials for Xilio’s product
candidates not supporting further development of such product
candidates; actions of regulatory agencies, which may affect the
initiation, timing and progress of current or future clinical
trials; Xilio’s ability to obtain, maintain and enforce patent and
other intellectual property protection for current or future
product candidates; Xilio’s ability to obtain and maintain
sufficient cash resources to fund current or future operating
expenses and capital expenditure requirements; the impact of
international trade policies on Xilio’s business, including U.S.
and China trade policies; and Xilio’s ability to seek, establish
and maintain a collaboration or partnership to develop XTX101 with
a collaborator or partner. These and other risks and uncertainties
are described in greater detail in the sections entitled “Risk
Factor Summary” and “Risk Factors” in Xilio’s filings with the U.S.
Securities and Exchange Commission (SEC), including Xilio’s most
recent Quarterly Report on Form 10-Q and any other filings
that Xilio has made or may make with the SEC in the future. Any
forward-looking statements contained in this press release
represent Xilio’s views only as of the date hereof and should not
be relied upon as representing its views as of any subsequent date.
Except as required by law, Xilio explicitly disclaims any
obligation to update any forward-looking statements.
This press release contains hyperlinks to
information that is not deemed to be incorporated by reference in
this press release.
For Investor Inquiries:
Melissa ForstArgot PartnersXilio@argotpartners.com
For Media Inquiries:
Julissa VianaVice President, Corporate
Communicationsmedia@xiliotx.com
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