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 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.