Aravive, Inc. (Nasdaq: ARAV) today announced new positive data from
the ongoing Phase 1b portion of the Phase 1b/2 clinical trial of
AVB-500 in platinum-resistant recurrent ovarian cancer patients.
The data from the first 31 patients treated at the 10mg/kg dose are
maturing and affirm earlier findings on the relationship between
AVB-500 levels and anti-tumor response. In this data analysis, high
serum drug levels of AVB-500 were strongly predictive of anti-tumor
activity with statistically significant correlation to
progression-free survival (PFS; p=0.0066). PFS is the primary
endpoint for platinum-resistant ovarian cancer clinical trials.
At the 10 mg/kg dose, patients that met or exceeded the minimal
efficacious concentration of AVB-500 demonstrated a greater than
four-fold increase in median PFS over those with low exposure (8.1
vs. 1.8 months; p=0.0016) and approximately two-fold improvement in
overall response rate (ORR; 29% vs. 14%), including one complete
response (CR). Patients who achieved sufficient AVB-500 exposure
also showed improvements in duration of response (from 7.6 to 3.9
months) and clinical benefit rate (82% vs. 43%), with reduced
chance of progressing by 3.2-fold (from 57% to 18%).
“Platinum-resistant ovarian cancer is one of the most difficult
diseases to treat, not only because of the poor prognosis, but
because of the toxicities associated with chemotherapies,” said
Katherine Fuh, M.D., Ph.D., Assistant Professor in Obstetrics and
Gynecology, Washington University School of Medicine, and an
investigator in the study. “The safety profile of AVB-500 along
with the emerging data showing improvement in clinical benefit rate
and progression-free survival, support the use of AVB-500 to change
the treatment landscape for these patients.”
The open-label, Phase 1b portion of the Phase 1b/2 clinical
trial of AVB-500 enrolled patients with platinum-resistant
recurrent ovarian cancer in two cohorts, one investigating a
combination of AVB-500 with pegylated liposomal doxorubicin (PLD)
and the other a combination with paclitaxel (PAC). All patients
were treated with 10mg/kg AVB-500 every other week. The company
previously reported drug exposure-response relationship among the
initial patients receiving 10 mg/kg.
The study identified a minimal efficacious concentration (MEC)
(trough level greater than 13.8 mg/L) that is consistent with at
least 95% target engagement based on independent pharmacokinetic
(PK) modeling. At the 10 mg/kg dose, 17 of 31 patients in the study
(approximately 50%) achieved the minimal efficacious concentration
after the first dose of AVB-500.
The baseline characteristics, demographics and safety parameters
were comparable between patients who achieved the minimal
efficacious concentration and those who fell below that threshold.
The analysis shows that the clinical benefit at this dose level in
the study can be primarily attributed to AVB-500 exposure.
The analysis of the best overall response by investigator
determined RECIST v1.1 criteria data are summarized in the table
below:
|
High AVB-500 Exposure* |
Low AVB-500 Exposure* |
Number of Patients (n) |
17 |
14 |
Complete Response (CR) |
1** (6%) |
0 |
Partial Response (PR) |
4 (24%) |
2 (14%) |
Overall Response (ORR, PR+CR) |
5 (29%) |
2 (14%) |
Stable Disease (SD) |
9 (53%) |
4 (28%) |
Progressive Disease (PD) |
3 (18%) |
8 (57%) |
Clinical Benefit (SD+PR) |
14 (82%) |
6 (43%) |
Median PFS (months) |
8.1 |
1.8 |
Median DOR (months) |
7.6 |
3.9 |
Number of patients still on study*** |
8 (47%) |
0 |
* High vs. Low is based on above or below MEC,
respectively**Needs to be confirmed with repeat scan*** As of Oct.
31, 2019
The company cautions that the data analyses were conducted on a
small patient population (n=31).
Other notable findings:
- The patient with CR that is pending confirmation achieved the
MEC of AVB-500 and was on paclitaxel. She had a baseline serum GAS6
level typical of the platinum-resistant ovarian cancer population
and two-fold higher than that observed in healthy volunteers. She
also exhibited poor prognostic factors, including two prior lines
of therapy and platinum-free interval of less than three
months.
- Among the patients who responded to AVB-500, four of seven
remain responders and continue on study, and two patients remain on
AVB-500 as a single agent. All four patients achieved the minimal
efficacious AVB-500 concentration.
- Among the 13 patients whose best response was SD, four achieved
the MEC of AVB-500 and remain on study. One SD patient, whose
trough level was below the minimal efficacious concentration, did
not progress but withdrew consent. Because the study is still
ongoing and includes only patients above the MEC, duration of
response and PFS may continue to evolve.
“The strong exposure-response relationship suggests that AVB-500
is adding to the clinical benefit experienced by patients on
standard of care therapy,” said Gail McIntyre, Ph.D., chief
scientific officer of Aravive. “The improvements in
progression-free survival with AVB-500 bodes well for future
studies where that will be the primary endpoint measured to support
regulatory filing.”
These data confirm the company’s strategy to investigate higher
doses in the current Phase 1b study, to determine if a greater
proportion of patients can exceed the MEC. According to our
modeling, a dose of 20 mg/kg should allow greater than 90% of the
patients to achieve the MEC. It is anticipated 6 to 12 patients
will be treated with 15mg/kg and an additional 12 patients will be
treated with 20mg/kg. An independent safety monitoring group will
review data from the 15mg/kg group prior to escalation to the
20mg/kg dose.
AVB-500 continues to be well-tolerated and there have been no
serious and unexpected adverse reactions or dose-limiting
toxicities to date.
Conference Call Information: Aravive will
host a live conference call and webcast at 8:00 a.m.
ET today to discuss these clinical data. The conference call
may be accessed by dialing (844) 281-9845 (domestic) and (314)
888-4254 (international) and referring to conference ID 2965263. 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 AVB-500AVB-500 is a therapeutic
recombinant fusion protein that has been shown to neutralize GAS6
activity by binding to GAS6 with very high affinity. In doing so,
AVB-500 selectively inhibits the GAS6-AXL signaling pathway. In
preclinical studies, GAS6-AXL inhibition has shown anti-tumor
activity, both as a single agent and 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 is correlated to poor prognosis and survival, and has been
implicated in therapeutic resistance to conventional
chemotherapeutics and targeted therapies.
Aravive reported positive data from the expansion cohort in the
Phase 1b portion of a Phase 1b/2 clinical trial of AVB-500 in
platinum-resistant recurrent ovarian cancer. AVB-500 continues to
be well tolerated with no dose limiting toxicities. An
investigator-sponsored Phase 1 study of AVB-500, in combination
with durvalumab in patients with platinum-resistant recurrent
epithelial ovarian cancer, is also ongoing. Based on AVB-500’s
safety profile and specifically targeted mechanism of action, this
drug candidate has the potential to be used both in combination
with existing therapies, as well as a maintenance drug. The U.S.
Food and Drug Administration granted Fast Track Designation to
AVB-500 in platinum-resistant recurrent ovarian cancer.
About Aravive Aravive, Inc. (Nasdaq: ARAV)
is a clinical-stage biopharmaceutical company developing treatments
designed to halt the progression of life-threatening diseases,
including cancer and fibrosis. Aravive’s lead product candidate,
AVB-500, is an ultra-high affinity decoy protein that targets the
GAS6-AXL signaling pathway. By capturing serum GAS6, AVB-500
starves the AXL pathway of its signal, potentially halting the
biological programming that promotes disease progression. AXL
receptor signaling plays an important role in multiple types of
malignancies by promoting metastasis, cancer cell survival,
resistance to treatments, and immune suppression. The GAS6-AXL
signaling pathway also plays a significant role in fibrogenesis.
Aravive is evaluating AVB-500 in platinum-resistant ovarian cancer
and intends to expand development into additional oncology and
fibrotic indications. Aravive is based in Houston, Texas and
received a Product Development Award from the Cancer Prevention
& Research Institute of Texas (CPRIT) in 2016. For more
information, please visit www.aravive.com.
Forward-Looking Statements This communication
contains forward-looking statements (including within the meaning
of Section 21E of the United States Securities Exchange Act of
1934, as amended, and Section 27A of the United States Securities
Act of 1933, as amended), express or implied, concerning the strong
exposure-response relationship suggesting that AVB-500 is adding to
the clinical benefit experienced by patients on standard of care
therapy, the safety profile of AVB-500 along with the improvement
in clinical benefit rate and progression-free survival supporting
the use of AVB-500 to change the treatment landscape for these
patients, the improvements in progression-free survival with
AVB-500 boding well for future pivotal studies where that will be
the primary endpoint measured to support regulatory filing, a dose
of 20 mg/kg should allow 90% or greater of the patients to achieve
the desired high drug exposure levels, the existence of a dose
response relationship with AVB-500, the potential of AVB-500 to be
used both in combination with existing therapies, as well as a
maintenance drug, the potential of AVB-500 to halt the biological
programming that promotes disease progression and the expansion of
the development of AVB-500 into additional oncology and fibrotic
indications. 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 expand development in 2019 into additional
oncology and fibrotic indications, the Company’s dependence upon
AVB-500, AVB-500’s ability to have favorable results in clinical
trials or receive regulatory approval, potential delays in the
Company's clinical trials due to regulatory requirements or
difficulty identifying qualified investigators or enrolling
patients; 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 and Form
10-K/A for the fiscal year ended December 31, 2018, 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.
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/e1c0c0cf-1964-49a0-bc8b-4ca5f3e2cc8d
Contacts for Aravive:
Investors:
Christina Tartaglia
Stern Investor Relations
christina@sternir.com
Media:
Heidi Chokeir
Canale Communications
heidi@canalecomm.com
619-203-5391
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