Aravive Inc. (Nasdaq: ARAV), a clinical-stage oncology company
developing innovative therapeutics to treat life-threatening
diseases, today announced the Company has dosed the first patient
in its Phase 3 trial of AVB-500 in platinum resistant ovarian
cancer (PROC). The trial is evaluating the efficacy of AVB-500 in
combination with paclitaxel (chemotherapy) and the primary endpoint
is progression free survival.
In the Phase 1b clinical trial, AVB-500 was well-tolerated with
a favorable safety profile and had promising clinical responses in
patients who achieved minimal efficacious concentration (MEC) in a
subset analysis, which supported the Phase 3 trial design.
“AVB-500 provides a novel and differentiated approach to target
the GAS6/AXL pathway, which we know is commonly overactive in
ovarian cancer and responsible for some of the mechanisms of
resistance that lead to poor outcomes for patients who have an
urgent need for more effective therapies to halt the progression of
the disease,” said Katherine Fuh, M.D., Ph.D., Associate Professor,
Department of Obstetrics and Gynecology, Division of Gynecologic
Oncology, Center for Reproductive Health Sciences, Washington
University School of Medicine, St. Louis, MO. “This Phase 3 trial
will enable us to evaluate the impact of AVB-500 in improving
responses to chemotherapy among women with platinum resistant
tumors with the goal of extending patient survival.”
Aravive has simplified the Phase 3 trial’s statistical analysis
plan to include a single prospectively defined interim analysis to
determine whether randomization will continue with all patients,
regardless of prior bevacizumab treatment, or only with patients
medically ineligible to receive bevacizumab or who chose not
to receive bevacizumab. The final analysis of the primary
endpoint preserves the opportunity to evaluate the efficacy in
patients who received bevacizumab prior to study entry, as well as
those patients who never received bevacizumab. This provides an
additional opportunity to be successful in both patient
populations, regardless of the results of the interim analysis.
Analysis of pretreatment serum sAXL/GAS6 will be conducted to
determine whether it can identify patients who benefit from AVB-500
plus paclitaxel, but it will not be used in an interim analysis to
select patients since the Company believes the trial, which is
expected to enroll 300-400 patients, is well-powered for the
anticipated treatment effect without the need for biomarker
enrichment. The primary endpoint of the trial remains progression
free survival by RECIST 1.1, a standard method of assessing
clinical activity in this patient population and the accepted
regulatory endpoint for full approval. The secondary endpoint is
overall survival.
“The registrational AVB-500 Phase 3 trial, if successful, should
be sufficient to submit a Biologics License Application for PROC.
We remain on track to conduct the interim analysis in the first
quarter of next year,” said Reshma Rangwala, M.D., Ph.D., Chief
Medical Officer of Aravive. “We are pleased to announce the first
patient dosing of AVB-500, and we are excited about the meaningful
difference AVB-500 may provide for patients with advanced stage
difficult-to-treat ovarian cancer. This is an important milestone
for the Company, and we remain steadfast in our commitment to
bringing safe and differentiated treatment options to the oncology
community. We are enthusiastic about our AVB-500 development
program, which we believe has significant potential in multiple
therapeutic combinations across a broad range of diseases.”
About the Phase 3 PROC Trial
The global, randomized, double-blind, placebo-controlled
adaptive trial (GOG-3059/ENGOT OV-66) is designed to evaluate
efficacy and safety of AVB-500 at a dose of 15 mg/kg in combination
with paclitaxel. The trial is expected to enroll approximately
300-400 patients with high-grade serous ovarian cancer who have
received one to four prior lines of therapy at approximately 165
sites in the U.S. and Europe. The primary endpoint for the trial is
progression free survival and the secondary endpoint is overall
survival. Exploratory endpoints include objective response rate,
duration of response, quality of life, clinical benefit rate,
pharmacokinetic and pharmacodynamic profile, and sAXL/GAS6 ratio. A
prospectively defined interim analysis will determine whether
randomization will continue with all patients, regardless of prior
bevacizumab treatment, or only with patients medically ineligible
to receive bevacizumab or who chose not to receive
bevacizumab. This trial is being conducted in partnership with The
GOG Foundation, Inc. (GOG-F), through the GOG Partners program in
the USA and in partnership with the European Network for
Gynaecological Oncological Trial (ENGOT) groups in Europe. The
Phase 3 trial is listed on clinicaltrials.gov NCT04729608.
Conference Call Information
Aravive will host a conference call and webcast at 8:30 a.m. ET
today to discuss the trial design for its Phase 3 trial of AVB-500
in platinum resistant ovarian cancer. The conference call may be
accessed by dialing (844) 281-9845 (domestic) and (314) 888-4254
(international) and referring to conference ID 5757006. A webcast
of the conference call will be available in the Investors section
of the Aravive website at https://ir.aravive.com/. The archived
webcast will be available on Aravive’s website after the conference
call.
About Ovarian Cancer
Ovarian cancer ranks fifth in cancer deaths among women, and it
is estimated that there will be approximately 21,410 new cases of
ovarian cancer in the United States in 2021. Due to the nonspecific
nature of disease symptoms and lack of validated screening tools in
the general population, most women present with advanced disease.
Although aggressive cytoreductive surgery and platinum- and
taxane-based combination chemotherapy can place most patients into
remission, disease recurrence manifests in greater than 70% of
patients. Ultimately, patients who relapse become
platinum-resistant and the identification of effective and
tolerable treatment options is considered a high unmet clinical
need.
About AVB-500
AVB-500 is a therapeutic recombinant fusion protein that has
been shown to neutralize GAS6 activity by binding to GAS6 with very
high affinity in preclinical models. In doing so, AVB-500
selectively inhibits the GAS6-AXL signaling pathway, which is
upregulated in multiple cancer types including ovarian cancer. In
preclinical studies, GAS6-AXL inhibition has shown anti-tumor
activity in combination with a variety of anticancer therapies,
including radiation therapy, immuno-oncology agents, and
chemotherapeutic drugs that affect DNA replication and repair.
Increased expression of AXL and GAS6 in tumors has been correlated
with poor prognosis and decreased survival and has been implicated
in therapeutic resistance to conventional chemotherapeutics and
targeted therapies. AVB-500 is currently being evaluated in
clinical trials and has been granted Fast Track Designation by the
U.S. Food and Drug Administration in platinum resistant recurrent
ovarian cancer. Analysis of all safety data to date showed that
AVB-500 has been generally well-tolerated with no dose-limiting
toxicities or unexpected safety signals.
About Aravive
Aravive, Inc. is a clinical-stage oncology company developing
innovative therapeutics designed to halt the progression of
life-threatening diseases. Aravive is based in Houston, Texas and
received a Product Development Award from the Cancer Prevention
& Research Institute of Texas (CPRIT) in 2016. Aravive’s lead
therapeutic, AVB-500, is an ultra-high affinity decoy protein that
targets the GAS6-AXL signaling pathway associated with tumor cell
growth. Aravive successfully completed a Phase 1b trial of AVB-500
in platinum resistant ovarian cancer and has initiated a
registrational Phase 3 trial of AVB-500 at a dose of 15 mg/kg.
While the Phase 1b trial of AVB-500 in platinum resistant ovarian
cancer was a safety trial and not powered to demonstrate efficacy,
all 5 patients in the 15 mg/kg cohort experienced clinical benefit,
with 1 complete response, 2 partial responses, and 2 stable
disease. The Company is dosing patients in its registrational Phase
3 trial in platinum resistant ovarian cancer and Phase 1b/2 trial
in clear cell renal cell carcinoma. For more information, please
visit www.aravive.com.
About the GOG Foundation, Inc.
(www.gog.org)
The GOG Foundation, Inc. (GOG Foundation) is a not-for-profit
organization with the purpose of promoting excellence in the
quality and integrity of clinical and translational scientific
research in the field of gynecologic malignancies. The GOG
Foundation is committed to maintaining the highest standards in
clinical trials development, execution, analysis and distribution
of results. The GOG Foundation is the only clinical trialist group
in the United States that focuses its research on women with pelvic
malignancies, such as cancer of the ovary (including surface
peritoneal malignancies), uterus (including endometrium, soft
tissue sarcoma, and gestational trophoblastic neoplasia), cervix,
and vulva. The GOG Foundation is multi-disciplinary in its approach
to clinical trials, and includes gynecologic oncologists, medical
oncologists, pathologists, radiation oncologists, oncology nurses,
biostatisticians (including those with expertise in
bioinformatics), basic scientists, quality of life experts, data
managers, and administrative personnel.
About GOG Partners
Supported by industry, GOG Partners has been structured to work
directly with pharmaceutical organizations and operate clinical
trials outside the National Cancer Institute (NCI) framework. By
providing an alternative venue for patient accrual and site
infrastructure support, GOG Partners has helped stabilize the
national gynecologic clinical trials network.
About ENGOT Groups
ENGOT is a pan-European Network of Gynaecological Oncological
Trial Groups supported by and part of the European Society of
Gynaecological Oncology (ESGO). ENGOT is a network of national and
regional clinical trial units that coordinates and promotes
clinical trials within Europe for women with gynaecological cancer.
This coordination is particularly relevant for academic clinical
trials, translational research, research on rare diseases, and for
clinical trials sponsored by industry to perform multinational
studies in Europe.
ENGOT consists of 21 European trial groups that perform
cooperative clinical trials. ENGOT is a platform that
guarantees that the European spirit and culture is incorporated
into the medical progress in gynaecological oncology, and that all
European patients and countries can participate in an active way in
clinical research and progress.
ENGOT's mission is to bring the best treatment to gynaecological
cancer patients through the best science and enabling every patient
in every European country to access a clinical trial.
Forward-Looking Statements
This communication contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. In some cases, forward-looking statements can be identified
by terminology such as "may," "should," "potential," "continue,"
"expects," "anticipates," "intends," "plans," "believes,"
"estimates," and similar expressions and includes statements
regarding enrolling 300-400 patients at approximately 165 sites in
the U.S. and Europe in a simplified adaptive trial design, AVB-500
extending patient survival, the registrational AVB-500 Phase 3
trial, if successful, being sufficient to file the Biologics
License Application for PROC, remaining on track to conduct an
interim analysis in the first quarter of next year, AVB-500
providing a meaningful difference for patients with advanced stage
difficult-to-treat ovarian cancer, the trial being well-powered for
the anticipated treatment effect without the need for biomarker
enrichment and the AVB-500 development program having significant
potential in multiple therapeutic combinations in a broad range of
diseases. Forward-looking statements are based on current beliefs
and assumptions, are not guarantees of future performance and are
subject to risks and uncertainties that could cause actual results
to differ materially from those contained in any forward-looking
statement as a result of various factors, including, but not
limited to, risks and uncertainties related to: the Company’s
ability to recruit for and enroll the expected number of patients
into the Phase 3 trial of AVB-500 in PROC as planned and
sufficiently power the trial, the Company’s ability to conduct an
interim analysis in the first quarter of next year and file a
Biologics License Application for PROC based on the Phase 3 data,
the impact of COVID-19 on the Company's clinical strategy, clinical
trials, supply chain and fundraising, the Company's ability to
expand development into additional oncology indications, the
Company's dependence upon AVB-500, AVB-500's ability to have
favorable results in clinical trials and ISTs, the clinical trials
of AVB-500 having results that are as favorable as those of
preclinical and clinical trials, the ability to receive regulatory
approval, potential delays in the Company's clinical trials due to
regulatory requirements or difficulty identifying qualified
investigators or enrolling patients especially in light of the
COVID-19 pandemic; the risk that AVB-500 may cause serious side
effects or have properties that delay or prevent regulatory
approval or limit its commercial potential; the risk that the
Company may encounter difficulties in manufacturing AVB-500; if
AVB-500 is approved, risks associated with its market acceptance,
including pricing and reimbursement; potential difficulties
enforcing the Company's intellectual property rights; the Company's
reliance on its licensor of intellectual property and financing
needs. The foregoing review of important factors that could cause
actual events to differ from expectations should not be construed
as exhaustive and should be read in conjunction with statements
that are included herein and elsewhere, including the risk factors
included in the Company's Annual Report on Form 10-K for the fiscal
year ended December 31, 2020, recent Current Reports on Form 8-K
and subsequent filings with the SEC. Except as required by
applicable law, the Company undertakes no obligation to revise or
update any forward-looking statement, or to make any other
forward-looking statements, whether as a result of new information,
future events or otherwise.
Contact: Joseph SchepersVP, Investor Relations,
Aravive, Inc. jschepers@aravive.com(770) 558-5517
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