Batiraxcept (AVB-S6-500)/Placebo in Combination With Paclitaxel in Patients With Platinum-Resistant Recurrent Ovarian Cancer (AXLerate-OC)

• ClinicalTrials.gov Identifier: NCT04729608
• Recruitment Status: Active, not recruiting
• First Posted: January 28, 2021
• Last Update Posted: March 23, 2023
• Sponsor: Aravive, Inc.
• Collaborators: GOG Foundation; European Network of Gynaecological Oncological Trial Groups (ENGOT)
• Information provided by (Responsible Party): Aravive, Inc.

Tracking Information

• First Submitted Date: January 25, 2021
• First Posted Date: January 28, 2021
• Last Update Posted Date: March 23, 2023
• Actual Study Start Date: April 22, 2021
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2022)

Anti-tumor activity of batiraxcept in combination with PAC measured by progression free survival (PFS) in patients receiving batiraxcept + PAC versus patients receiving Placebo+PAC [ Time Frame: 4 months ]

PFS is the time interval between randomization and radiologically documented disease progression or death, whichever comes first.

Original Primary Outcome Measures (submitted: January 27, 2021)

Anti-tumor activity of AVB-S6-500 in combination with Pac measured by progression free survival (PFS) in patients receiving AVB-S6-500+ Pac versus patients receiving Placebo+Pac [ Time Frame: 4 months ]

PFS is the time interval between randomization and radiologically documented disease progression or death, whichever comes first.

Current Secondary Outcome Measures (submitted: September 22, 2021)

Overall survival [ Time Frame: 20 months ]

Time following the treatment until death

Original Secondary Outcome Measures (submitted: January 27, 2021)

• Overall survival [ Time Frame: 20 months ]
  Time following the treatment until death
• Objective response rate (ORR) [ Time Frame: 3 months ]
  Proportion of subjects who have a confirmed partial or complete response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
• Duration of response (DOR) [ Time Frame: 9 months ]
  Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria.
• Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 10 months ]
• Quality of Life (QOL) [ Time Frame: 10 months ]
  Subject QOL will be assessed using the Functional Assessment Of Cancer Therapy - Ovarian Cancer (FACT-O) questionnaire, which consists of 4 subscales: physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), and functional well-being (7 questions), and 12 additional concerns specific to ovarian cancer. All items are rated on a 5 point scale with 0 "not at all" and 4 "very much". The scoring algorithm allows for eight summary scales: the four core well-being subscales, a subtotal of the 27 core items, a subtotal of the 12 ovarian-specific additional concerns, a grand total of the 39 items, and a trial outcome index (sum of the 17 physical and functional wellbeing items plus the 12 ovarian-specific items).
• Clinical benefit rate (CBR) [ Time Frame: 4 months ]
• Area under the AVB-S6-500 concentration-time curve. [ Time Frame: 10 months ]
• Maximum observed AVB-S6-500 concentration. [ Time Frame: 10 months ]
• Time of maximum observed AVB-S6-500 concentration. [ Time Frame: 10 months ]
• Half-life of AVB-S6-500. [ Time Frame: 10 months ]
• Pharmacodynamic marker assessment [ Time Frame: 10 months ]
  Change from the baseline in GAS6 serum levels.
• Anti-drug antibody (ADA) titers [ Time Frame: 10 months ]

Current Other Pre-specified Outcome Measures (submitted: June 27, 2022)

• Duration of response (DOR) [ Time Frame: 9 months ]
  Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria.
• Objective response rate (ORR) [ Time Frame: 3 months ]
  Proportion of subjects who have a confirmed partial or complete response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
• Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 10 months ]
• Quality of Life (QOL) [ Time Frame: 10 months ]
  Subject QOL will be assessed using the Functional Assessment Of Cancer Therapy - Ovarian Cancer (FACT-O) questionnaire, which consists of 4 subscales: physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), and functional well-being (7 questions), and 12 additional concerns specific to ovarian cancer. All items are rated on a 5 point scale with 0 "not at all" and 4 "very much". The scoring algorithm allows for eight summary scales: the four core well-being subscales, a subtotal of the 27 core items, a subtotal of the 12 ovarian-specific additional concerns, a grand total of the 39 items, and a trial outcome index (sum of the 17 physical and functional wellbeing items plus the 12 ovarian-specific items).
• Clinical benefit rate (CBR) [ Time Frame: 4 months ]
• Area under the batiraxcept concentration-time curve. [ Time Frame: 10 months ]
• Maximum observed batiraxcept concentration. [ Time Frame: 10 months ]
• Minimum observed batiraxcept concentration. [ Time Frame: 10 months ]
• Pharmacodynamic marker assessment [ Time Frame: 10 months ]
  Change from the baseline in GAS6 serum levels.
• Anti-drug antibody (ADA) titers [ Time Frame: 10 months ]
• Cancer antigen 125 (CA-125) levels [ Time Frame: 10 months ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Batiraxcept (AVB-S6-500)/Placebo in Combination With Paclitaxel in Patients With Platinum-Resistant Recurrent Ovarian Cancer
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo/Paclitaxel-Controlled Study of Batiraxcept (AVB-S6-500) in Combination With Paclitaxel in Patients With Platinum-Resistant Recurrent Ovarian Cancer (AXLerate-OC)
• Brief Summary: This is a randomized, double-blind Phase 3 study to compare the efficacy and safety of batiraxcept (AVB-S6-500) in combination with paclitaxel (PAC) versus placebo in combination with PAC in patients with platinum resistant recurrent ovarian cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Platinum-resistant Ovarian Cancer

Intervention

• Drug: Batiraxcept
  Batiraxcept is an experimental drug
  Other Name: AVB-S6-500
• Drug: Paclitaxel
  Paclitaxel is the standard of care, background therapy
  Other Name: Taxol
• Other: Placebo
  Matching placebo

Study Arms

• Experimental: Batiraxcept+PAC
  Combination of batiraxcept and PAC
  Interventions:

  • Drug: Batiraxcept
  • Drug: Paclitaxel
• Placebo Comparator: Placebo+PAC
  Placebo-controlled arm with PAC
  Interventions:

  • Drug: Paclitaxel
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: June 27, 2022): 350
• Original Estimated Enrollment (submitted: January 27, 2021): 500
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed and documented recurrent ovarian, fallopian tube, or peritoneal cancer. Only patients with high-grade serous adenocarcinoma histology are eligible.
• Aged 18 years or older
• Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 1
• Platinum-resistant disease (defined as progression within ≤6 months from completion of most recent platinum-containing regimen and calculated from the date of the last administered dose of platinum therapy).Subject may have been treated with additional regimen(s) subsequent to determination of platinum resistance.
• Available archived tumor tissue or if archived tissue is not available, a fresh tumor biopsy.
• Received at least 1 but not more than 4 prior therapy regimens.

Note: Maintenance therapy OR hormonal therapies should not be counted as a separate therapy.

Note: Patients who have not received prior bevacizumab must be deemed medically inappropriate OR ineligible to receive bevacizumab, refused to receive bevacizumab, or been unable to receive bevacizumab due to lack of access.

• Measurable disease according to RECIST v1.1 criteria
• Normal gastrointestinal function.
• At least 28 days between termination of prior anticancer or hormonal therapy and first administration of batiraxcept.
• Full recovery from all treatment-related toxicities to Grade 1 or less, except alopecia.

Exclusion Criteria:

• Tumors in the breast or bone
• Untreated central nervous system (CNS) metastases. Subjects requiring corticosteroid therapy for the management of their treated CNS metastases may not be on >10 mg/day prednisone or equivalent or have demonstrated signs or symptoms of neurologic instability for 28 days or less prior to randomization.
• Primary platinum-refractory disease (defined as progression during or within 4 weeks after completion of the first platinum regimen)
• Is being treated with concurrent anticancer therapy or other interventional treatments administered for their underlying ovarian cancer.
• Received prior therapy with PAC in the platinum-resistant recurrent setting
• Evidence of clinically significant third spacing (e.g., pleural effusions, ascites, anasarca, etc.) that requires therapeutic intervention within 28 days prior to first dose of batiraxcept/placebo

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, China, Czechia, France, Georgia, Italy, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04729608
• Other Study ID Numbers: AVB500-OC-004; GOG-3059 ( Other Identifier: GOG Foundation ); ENGOT OV66 ( Other Identifier: ENGOT ); AXLerate-OC ( Other Identifier: Aravive )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Aravive, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Aravive, Inc.
• Original Study Sponsor: Same as current

Collaborators

• GOG Foundation
• European Network of Gynaecological Oncological Trial Groups (ENGOT)

• Investigators: Not Provided
• PRS Account: Aravive, Inc.
• Verification Date: March 2023