The first patient has been dosed in a phase 1b/2 trial of AVB-500, a therapeutic recombinant fusion protein, in combination with gemcitabine and nab-paclitaxel for the treatment of advanced pancreatic adenocarcinoma.
The first patient has been dosed in a phase 1b/2 trial of AVB-500, a therapeutic recombinant fusion protein, in combination with gemcitabine (Gemzar) and nab-paclitaxel (Abraxane) for the treatment of advanced pancreatic adenocarcinoma, according to a press release by Aravive Inc.1
AVB-500 is meant to neutralize GAS6 by binding to it, which selectively inhibits the GAS6-AXL signaling pathway. This pathway is upregulated in multiple cancer types such as renal, ovarian, and pancreatic cancer. Inhibition of this pathway has proven anti-tumor activity in a variety of therapies including radiation, immune-oncology agents, and chemotherapy agents. Increased expression of AXL and GAS6 is associated with a poor prognosis and decreased survival.
The single-group, randomized, open-label study (NCT04983407) has an estimated enrollment of 80 participants and an estimated completion date of April 2024. Primary end points include the incidence of adverse events up to 12 months and the antitumor activity of the agent in combination with nab-paclitaxel and gemcitabine at 12 and 30 months. Secondary end points include pharmacokinetics, anti-drug antibody titers, disease control rate, duration of response, overall survival.2
During phase 1b, patients will receive the experimental combination. This arm will enroll approximately 20 patients who will receive a dose of 15mg/kg of AVB-500. Phase 2 will be split into 2 arms and will enroll approximately 60 patients total. The experimental arm of phase 2, patients will receive AVB-500 at 15mg/kg in combination with nab-paclitaxel and gemcitabine. In the control arm, patients will receive nab-paclitaxel and gemcitabine alone.
In order to participate, patients must be 18 years old or older, have histologically or cytologically confirmed pancreatic adenocarcinoma that is locally advanced, recurrent, or metastatic and is ineligible for curative intent treatments and eligible for first-line systemic treatment, must have radiological imaging, have at least one measurable lesion according to RECIST 1.1, an ECOG performance status of 0 to 1, have adequate gastrointestinal, bone marrow, liver, and kidney function, a life expectancy minimum of >12 weeks, and adequate recovery from surgery to Grade 1 or baseline with a least 28 days from time of major surgery.
Patients who received the last dose of chemotherapy, surgery, or radiation treatment with curative intent within 6 months prior to study entry, lslet-cell neoplasms, a prior malignancy within the past 3 years, symptomatic uncontrolled central nervous system metastasis or brain metastases unless adequately treated and controlled, have evidence of clinically significant third spacing, serious active infection, or active HIV infection are not eligible to participate.
“We are pleased with the quick advancement of AVB-500 with the first patient dosed in our Phase 1b/2 pancreatic adenocarcinoma trial. This clinical trial addresses a very high unmet medical need in one of the most difficult-to-treat cancers with a high mortality rate,” said Gail McIntyre, PhD, DABT, chief executive officer of Aravive in a press release. “We continue to expand the development of AVB-500, as the Company now has three ongoing clinical trials of AVB-500. In addition to the pancreatic adenocarcinoma clinical trial, AVB-500 is currently being investigated in a Phase 3 clinical trial for platinum resistant ovarian cancer and a Phase 1b/2 clinical trial for clear cell renal cell carcinoma.”
The study is being conducted across 17 locations in various states including, California, Florida, Michigan, New York, North Carolina, Ohio, Oregon, Pennsylvania, Virginia, and Wisconsin.