– PD-L1 Targeting Probody CX-072 Well
Tolerated and Shows Antitumor Activity as Monotherapy and in
Combination with Ipilimumab –
CytomX Therapeutics, Inc. (Nasdaq:CTMX) a clinical-stage
oncology-focused biopharmaceutical company pioneering a novel class
of investigational antibody therapeutics based on its Probody™
therapeutic technology platform, today presented preliminary
clinical results from two arms of the PROCLAIM
(
PRObody
CLinical
Assessment
In
Man) module, PROCLAIM-072. PROCLAIM-072 is an
ongoing Phase 1/2 trial evaluating CX-072, a Probody therapeutic
targeting PD-L1, as monotherapy and in combination with Yervoy®
(ipilimumab) or Zelboraf® (vemurafenib) in patients with advanced,
unresectable solid tumors. Data from the CX-072 monotherapy arm and
ipilimumab combination arm were presented today in two posters as
part of the Developmental Therapeutics—Immunotherapy Session at the
2018 Annual Meeting of the American Society of Clinical Oncology
(ASCO) in Chicago, Illinois.
“These first clinical results mark a major milestone for CytomX
as we advance our Probody platform and introduce a fundamentally
new approach to antibody therapeutic drug development,” said Sean
McCarthy D.Phil., president and chief executive officer of CytomX
Therapeutics. “The findings presented today show that our lead
wholly-owned program, the PD-L1 targeting Probody therapeutic,
CX-072, has the potential to become a new centerpiece of
combination cancer therapy. These preliminary results suggest that
CX-072 as monotherapy and in combination with ipilimumab has a
favorable safety profile and encouraging antitumor efficacy in
late-stage, heavily pretreated cancer patients. Moreover, these
clinical data check important boxes for the development of our core
platform technology by showing that CX-072 remains stable in
circulation over extended periods of dosing and elicits anti-tumor
effects within the tumor microenvironment. Based on these initial
results, we have initiated multiple monotherapy expansion cohorts
to further explore the safety and efficacy of this potentially
differentiated PD-L1 inhibitor.”
Preliminary Results of the First-In-Human, Dose-Finding
PROCLAIM-072 Trial of the PD-L1 Probody Therapeutic CX-072 as
Monotherapy in Patients with Advanced Solid Tumors
Session: Developmental
Therapeutics—Immunotherapy (Poster #285)
Presenter: Karen A. Autio, M.D., MSc., Memorial
Sloan Kettering Cancer Center
The primary objectives of this first-in-human, dose-escalation,
monotherapy arm are to assess safety and tolerability, including
determination of the maximum tolerated dose (MTD) and the
dose-limiting toxicity (DLT) of CX-072 as monotherapy. At the
completion of escalation, the arm had enrolled 22 patients, with an
average of four prior anti-cancer treatments in a variety of tumor
types for which no anti-PD-1 or anti-PD-L1 agents are available for
their disease. Patients received escalating doses of CX-072 from
0.03 mg/kg to 30 mg/kg. Enrollment is complete and patient
follow-up is ongoing.
Monotherapy Well Tolerated
The maximum tolerated dose (MTD) was not reached. As of an
April 20, 2018 data cutoff, results showed that the administration
of monotherapy CX-072 was well tolerated with the majority of
treatment-related adverse events (TRAEs) as Grade 1/2. Grade 3/4
TRAEs were reported in two patients: neutropenia and
thrombocytopenia in a patient with thymic cancer (3 mg/kg) and
transaminase elevation in a patient with breast cancer (30 mg/kg).
Both events were successfully managed with therapeutic intervention
including steroids and discontinuation of CX-072.
Evidence of Activity
As of an April 20, 2018 data cutoff, results showed that among
20 evaluable patients who received CX-072, objective responses by
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1,
a commonly used guideline for evaluating tumors, were observed in 3
(15%) patients: thymoma (unconfirmed PR (uPR); 3 mg/kg), PD-L1
negative TNBC (confirmed PR; 10 mg/kg) and cervical cancer (uPR; 10
mg/kg) (all partial responses (PR)). Stable disease was
observed in 8 patients (40%) for a disease control rate of 55%.
Decreased target lesions were observed in 42% (8/19) of all
evaluable patients with measurable disease at baseline and in 60%
(6/10) of the subset of patients who received > 3 mg/kg of
CX-072. Two of the responders were still on treatment (8 months
each) at the time of the data cutoff.
Evidence of Probody Platform Performance
Results from a preliminary single-dose pharmacokinetic analysis
of single-agent CX-072 suggest that, as designed, CX-072 circulates
predominantly as the intact masked prodrug across all dose levels.
Further, CX-072 is only minimally influenced by target mediated
drug disposition at low doses, suggesting that masking is effective
in blocking interaction with PD-L1 in the periphery.
Based on these preliminary safety, efficacy and translational
data, further evaluation of CX-072 monotherapy (10 mg/kg every two
weeks) is now underway in 8 expansion cohorts in a variety of
cancer types.
Preliminary Interim Results of the First-In-Human, Dose-Finding
PROCLAIM-072 Trial of the PD-L1 Probody Therapeutic CX-072 in
Combination with Ipilimumab in Patients with Advanced Solid
Tumors
Session: Developmental
Therapeutics—Immunotherapy (Poster #286)Presenter:
Rachel E. Sanborn, M.D., Earle A. Chiles Research Institute,
Providence Cancer Center
The primary objectives of this ongoing arm of the study are to
assess safety and tolerability, and to determine the MTD and DLT of
CX-072 when administered in a concomitant combination schedule with
ipilimumab. At the April 20, 2018 data cutoff, the study had
enrolled 16 immunotherapy naïve patients who had received an
average of four prior anti-cancer treatments in a variety of tumor
types for which no anti-PD-1 or PD-L1 agents were available for
their disease. Patients received the combination ipilimumab
(3 mg/kg) and CX-072 (escalating doses of 0.3 mg/kg to 10 mg/kg)
every three weeks for four cycles followed by monotherapy CX-072
every two weeks.
Combination with Ipilimumab Well Tolerated
As of the April 20, 2018 data cutoff date, the MTD had not yet
been reached and no new safety signals were observed beyond those
expected for each component of the ipilimumab plus CX-072
combination. The majority of TRAEs were Grade 1/2. Of
the 16 treated patients, 5 (31%) reported a Grade 3/4 TRAE, a rate
similar to that reported previously for 3 mg/kg ipilimumab
monotherapy1. These events included: Grade 3 colitis (n=1), Grade 3
dyspnea/pneumonitis (n=1), Grade 3 headache/Grade 3 hyponatremia
(n=1), and Grade 3 amylase/Grade 4 lipase (n=1)2. A dose limiting
toxicity of Grade 3 dyspnea was reported in one patient. The study
is still ongoing with enrollment and dose escalation
continuing.
Evidence of Activity
As of an April 20, 2018 data cutoff, results also showed that
among 12 evaluable patients who received ipilimumab (3 mg/kg)
combined with CX-072 (0.3 to 10 mg/kg), 3 (25%) achieved objective
responses by RECIST v1.1, including patients with: anal cancer
(confirmed complete response (CR); 0.3 mg/kg CX-072), testicular
cancer (uPR; 1 mg/kg CX-072) and cancer of unknown primary (uPR; 3
mg/kg CX-072). Stable disease was observed in 8% of patients
for a disease control rate of 33%. All 3 of the responders
remained on treatment (10, 6 and 5 months, respectively) at the
data cutoff.
Preliminary Single-Dose Clinical Pharmacokinetics of an
anti-PD-L1 Probody Therapeutic in Cancer Patients ASCO Supplement
of the Journal of Clinical Oncology [J Clin Oncol 36, 2018 (suppl;
abst 214558)]. (Abstract #e14558)
Preliminary pharmacokinetic clinical data showed that
single-agent, single-dose CX-072 behaved as designed and circulated
predominantly as the intact antibody prodrug and is only minimally
affected by target-mediated drug disposition, consistent with being
effectively masked in circulation.
Conference Call and Webcast
CytomX will host a conference call and live webcast with slides
today, Monday, June 4, 2018, beginning at 5:00 p.m. CT/ 6:00 p.m.
ET to discuss these data presentations. This event can be accessed
in three ways:
- From the CytomX website:
http://ir.cytomx.com/events-and-presentations. Please access the
website 15 minutes prior to the start of the call to download and
install any necessary audio software.
- By telephone: Participants can access the call by dialing
1-877-809-6037 (United States) or 1-615-247-0221 (International)
referencing Conference ID 4294667.
- By replay: A replay of the webcast will be located under the
Investor Relations section of CytomX’s website approximately two
hours after the conclusion of the live call and will be available
for 30 days following the call.
About PROCLAIM
PROCLAIM (Probody Clinical
Assessment In
Man) is an international umbrella program designed
to evaluate CytomX’s Probody therapeutics. The first module is the
PROCLAIM-CX-072 clinical program, an open-label, dose-finding Phase
1/2 trial evaluating CX-072 as monotherapy and in combination with
Yervoy® (ipilimumab) or Zelboraf®(vemurafenib) in patients with
metastatic or locally advanced unresectable solid tumors or
lymphomas. CytomX aims to achieve three goals as part of the
PROCLAIM-072 clinical trial:
- Tolerability: Demonstrate that CX-072 is well tolerated in
patients and potentially improves safety, particularly in the
combination setting.
- Anti-cancer activity: Demonstrate initial evidence of CX-072’s
anti-cancer activity as monotherapy and in combination.
- Translational program and Probody platform proof-of-concept:
Explore mechanistic aspects of Probody activity in patients as
observed in preclinical models.
About CytomX Therapeutics
CytomX Therapeutics is a clinical-stage oncology-focused
biopharmaceutical company pioneering a novel class of
investigational antibody therapeutics based on its Probody
therapeutic technology platform. Probody therapeutics are designed
to exploit unique conditions of the tumor microenvironment to more
effectively localize antibody binding and activity while limiting
activity in healthy tissues. The Company’s pipeline includes cancer
immunotherapies against clinically-validated targets, such as
CX-072, a PD-L1-targeting Probody therapeutic wholly-owned by
CytomX, BMS-986249, a CTLA-4-targeting Probody therapeutic
partnered with Bristol Myers Squibb, CX-188, a PD-1-targeting
Probody therapeutic wholly-owned by CytomX, and first-in-class
Probody drug conjugates against high potential targets, such as
CX-2009, a CD166-targeting Probody drug conjugate wholly-owned by
CytomX and CX-2029, a CD71-targeting Probody drug conjugate
partnered with AbbVie, which are considered to be inaccessible to
conventional antibody drug conjugates due to their presence on
healthy tissue. In addition to its wholly owned programs, CytomX
has strategic collaborations with AbbVie, Amgen, Bristol-Myers
Squibb Company, and ImmunoGen, Inc. For more information, visit
www.cytomx.com or follow us on Twitter.
CytomX Therapeutics Forward-Looking Statements
This press release includes forward-looking statements. Such
forward-looking statements involve known and unknown risks,
uncertainties and other important factors that are difficult to
predict, may be beyond our control, and may cause the actual
results, performance or achievements to be materially different
from any future results, performance or achievements expressed or
implied in such statements. Accordingly, you should not rely on any
of these forward-looking statements, including those relating to
the potential safety, benefits and efficacy of CX-072, administered
separately or in combination, the Company’s ability to develop and
advance CX-072 into and successfully complete clinical trials, and
the timing of any future clinical trials of CX-072. Risks and
uncertainties that contribute to the uncertain nature of the
forward-looking statements include: CytomX’s product candidates
under its Probody platform, including CX-072, are in the initial
stages of clinical development, the process by which preclinical
and clinical development could potentially lead to an approved
product is long and subject to significant risks and uncertainties;
the possibility that the results of early clinical trials may not
be predictive of future results; the possibility that CytomX’s
clinical trials will not be successful; possible regulatory
developments in the United States and foreign countries;
collaborations with partners may not result in products, and
milestone payments and royalties may not be received. Applicable
risks and uncertainties include those relating to our preclinical
research and development, clinical development, collaborations and
other risks identified under the heading "Risk Factors" included in
CytomX’s Quarterly Report on Form 10-Q filed with the SEC on May 9,
2018. The forward-looking statements contained in this press
release are based on information currently available to CytomX and
speak only as of the date on which they are made. CytomX does not
undertake and specifically disclaims any obligation to update any
forward-looking statements, whether as a result of any new
information, future events, changed circumstances or otherwise.
CytomX Therapeutics
Investors:
Christopher Keenan VP, Investor Relations and Corporate
Communications ckeenan@cytomx.com 650-383-0823
Media:
Spectrum Christine Quern cquern@spectrumscience.com
202-587-2588
1 Larkin J, et al. Combined nivolumab and ipilimumab or
monotherapy in untreated melanoma. N Engl J Med 2015;373:
23–34.
2 A Grade 3 TRAE in 1 patient was designated as nontreatment
related post data cutoff.
CytomX Therapeutics (NASDAQ:CTMX)
過去 株価チャート
から 6 2024 まで 7 2024
CytomX Therapeutics (NASDAQ:CTMX)
過去 株価チャート
から 7 2023 まで 7 2024