FDA Grants Fast Track Designation to AVB-001 for R/R Platinum-Resistant Ovarian Cancer

The FDA has granted fast track designation to AVB-001 for the treatment of adult patients with relapsed/refractory, platinum-resistant, high-grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube.¹

The encapsulated cell product is designed to produce native human interleukin-2 (hIL-2), and the agent is delivered as am intraperitoneal injection. AVB-001 leverages Avenge Bio’s LOCOcyte^™ immunotherapy platform, which generates potent immune effector molecules by synthetically engineering allogeneic cells. With the platform, therapy is localized to the primary tumor site, and it is designed to train the patient’s immune system to target distant metastases without systemic toxicity.

“We are extremely pleased to receive the FDA fast track designation for AVB-001 based on FDA's review of our preclinical and emerging clinical data,” Michael Heffernan, chief executive officer at Avenge Bio, said in a news release. “The fast track designation has been provided for platinum-resistant, refractory ovarian cancer, and acknowledges the potential for AVB-001 to treat this significant unmet medical need.”

The safety and early efficacy of ABV-001 is under investigation in an open-label, first-in-human, multicenter, phase 1/2 study (NCT05538624) that is enrolling patients at least 18 years of age with histologically confirmed, metastatic or unresectable, platinum-resistant, high-grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube who have not received more than 5 prior lines of therapy.² Prior treatment with a PARP inhibitor, bevacizumab (Avastin) or any other antiangiogenic agent, immunotherapy, or cell therapies is allowed. Notably, disease progression or intolerance to a PARP inhibitor is required for patients with germline or somatic BRCA mutations.

An ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria, an absolute neutrophil count greater than 1500/μL, a hemoglobin level of at least 9.0 g/dL, a platelet count of at least 100,000/μL, and a creatinine clearance of at least 50 mL/min are required.

Patients are not eligible for enrollment if they have low-grade serous, mucinous, clear cell, or endometrioid adenocarcinoma of the ovary, primary peritoneum, or fallopian tube, carcinosarcoma, or a mixed-histology tumor.

The phase 1/2 study is being conducted in 2 parts. Part 1 is comprised of dose escalation in up to 24 patients who will receive a single intraperitoneal dose of AVB-001 at 0.6, 1.2, 2.4, or 3.6 μg hIL-2/kg/day.

During dose expansion in part 2, up to 20 additional patients will receive a single dose of AVB-001 at the recommended phase 2 dose. Additional expansion cohorts may be introduced in part 2, which would evaluate AVB-001 as monotherapy or as part of an exploratory combination.

In part 1, the primary end points include the incidence of dose-limiting toxicities (DLTs) to determine the maximum tolerated dose and RP2D, and the incidence of treatment-emergent adverse effects (AEs) or serious AEs. The primary end point for part 2 is overall response rate (ORR) per RECIST v1.1 criteria.

Secondary end points for part 1 include ORR, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Secondary end points in part 2 consist of safety, DOR, PFS, and OS.

In April 2023, Avenge Bio announced the completion of the first dose level cohort of the phase 1/2 trial, where findings showed that AVB-001 was well tolerated. No DLTs, on-target or off-target toxicities, or other unexpected events were reported.³

The phase 2 dose-expansion portion of the trial is expected to initiate in 2024.¹

References

1. Avenge Bio receives FDA fast track designation for AVB-001, a novel cell therapy leveraging the LOCOcyte™ immunotherapy platform. News Release. Avenge Bio, Inc. October 2, 2023. Accessed October 2, 2023. https://avengebio.com/wp-content/uploads/2023/09/Avenge-Bio-Receives-FDA-Fast-Track-Designation-for-AVB-001
2. A study of intraperitoneally administered AVB-001 in patients with serous adenocarcinoma of the ovary. Updated March 21, 2023. Accessed October 2, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05538624
3. Avenge Bio Announces Successful Completion of First Dose Level Cohort in Phase 1/2 Clinical Trial of AVB-001 for the Treatment of Ovarian Cancer. News Release. Avenge Bio, Inc. April 23, 2023. Accessed October 2, 2023. https://avengebio.com/wp-content/uploads/2023/04/Avenge-Bio-Announces-Successful-Completion-of-First-Dose-Level-Cohort-in-Phase-1-2-Clinical-Trial-of-AVB-001-for-the-Treatment-of-Ovarian-Cancer.pdf