AVB-001 Encapsulated IL-2 Cell Therapy Shows Safety and Immune Activity in Platinum-Resistant HGSOC

A single intraperitoneal (IP) administration of AVB-001, an encapsulated, allogeneic cell product engineered to constitutively secrete human IL-2 (hIL-2), demonstrated a manageable safety profile and evidence of immune activation in patients with platinum-resistant high-grade serous ovarian carcinoma (HGSOC), according to results from a phase 1 dose-escalation trial (NCT05538624) published in Clinical Cancer Research.¹

Across 4 dose levels, 3 of 14 enrolled patients (21.4%) experienced grade 3 treatment-related adverse effects (TRAEs); no grade 4 or 5 TRAEs were reported. The confirmed objective response rate (ORR) was 0%, with 1 unconfirmed partial response that was not sustained at confirmatory imaging. Seven patients (50%) achieved stable disease (SD) with a median duration of 2.57 months (range, 2.03–4.23); 2 of those patients maintained SD beyond 4 months, yielding a clinical benefit rate (CBR) of 14.3%.

"In patients with HGSOC, AVB-001 is safe and effectively activates cytotoxic T cells, supporting further investigation of this locoregional immunotherapy," lead study author Shannon N. Westin, MD, MPH, and coauthors concluded in the publication.

Westin is a professor in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center in Houston.

What was the rationale for developing AVB-001 in this population?

Platinum-resistant HGSOC carries a median overall survival of approximately 12 months, and response rates to subsequent therapies decline with each successive line. The peritoneal cavity is the predominant site of metastasis in this disease, generating interest in IP drug delivery, which can achieve several-fold higher intra-abdominal drug concentrations compared with intravenous administration with a reduced systemic toxicity burden. Recombinant IL-2 delivered IP in earlier trials yielded an ORR of approximately 25% in platinum-resistant ovarian cancer but was complicated by catheter-related adverse effects and treatment discontinuation rates as high as 45%.

AVB-001 was designed to address these delivery limitations. The product consists of allogeneic retinal pigment epithelial cells engineered for constitutive hIL-2 secretion and encapsulated in alginate microspheres approximately 1.5 mm in diameter. Preclinical studies in murine ovarian cancer, colorectal cancer, and mesothelioma models demonstrated complete tumor regression and durable immunological memory following IP administration, and non-human primate (NHP) studies confirmed sustained local IL-2 production with minimal systemic distribution.

How was the phase 1 trial designed, and who was enrolled onto the study?

This open-label, multicenter phase 1 dose-escalation study enrolled patients with histologically confirmed, metastatic or unresectable, platinum-resistant or platinum-refractory high-grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube.^1,2 Patients were required to have measurable IP disease per RECIST 1.1 criteria on CT or MRI, an ECOG performance status of 0 or 1, and a maximum of 5 prior lines of therapy.

AVB-001 was administered in a single laparoscopic IP procedure, with capsules infused via an Argyle Tenckhoff peritoneal catheter at doses calibrated to deliver 0.6 to 3.6 μg hIL-2/kg/day. A Bayesian optimal interval (BOIN) design was used to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), targeting a dose-limiting toxicity (DLT) rate of approximately 30%.

Fourteen patients were enrolled onto the study between November 2022 and November 2023 across 4 dose cohorts: dose level 1 (n = 3), dose level 2 (n = 3), dose level 3 (n = 5), and dose level 4 (n = 3).¹ The median age was 68 years (range, 47–75); 78.6% had primary ovarian cancer, and all patients were White/Caucasian. The median number of prior lines of therapy was 2 (range, 1–4); 78.6% had received prior bevacizumab (Avastin), and 35.7% had received prior immunotherapy.

What were the pharmacokinetic and immunological findings?

Serum IL-2 concentrations peaked at 24 hours post-administration and declined to baseline by day 7, with peak levels increasing linearly across dose levels (R² = 0.74). A two-compartment pharmacokinetic model estimated IP IL-2 concentrations to be at least 7-fold higher than corresponding blood concentrations even with significant peritoneal fluid accumulation, and modeled IP levels were comparable to those achieved in prior peritoneal IL-2 infusion studies at their maximum tolerated doses.

Flow cytometric analysis of peripheral blood confirmed dose-dependent increases in CD8+/Ki67+, CD4+/Ki67+, and NK+/Ki67+ proliferating effector cells, all peaking at day 8 post-transplantation and returning to baseline by day 14. Critically, no increase in CD4+/FoxP3+ T-regulatory cells was observed across any dose level, a finding that distinguishes localized AVB-001 delivery from systemically administered IL-2, which has been associated with regulatory T-cell expansion that can suppress antitumor immune responses. CTLA-4 upregulation on both CD8+ and CD4+ T cells was dose-dependent and statistically significant, whereas PD-1 and TIM-3 expression trended upward without reaching significance. Because CTLA-4 upregulation at early time points has been characterized as an activation marker rather than a marker of exhaustion, investigators proposed that combining AVB-001 with anti–CTLA-4 checkpoint blockade may further amplify immune engagement.

Serum cytokine analyses revealed dose-dependent rises in IFN-γ, IP-10, CD25, and IL-6 following treatment. IFN-γ and IL-6 peaked at day 2, while IP-10 and CD25 peaked at day 8; CD25 remained elevated through day 30 at higher dose levels, suggesting sustained immune engagement. CA-125 showed an inverse trend with dose at day 29, with higher AVB-001 doses associated with attenuated CA-125 increases, though this did not reach statistical significance. Eosinophilia above the normal range was observed across all dose groups, consistent with IL-2's known role in eosinophil expansion.

What were the safety findings?

Eleven of 14 patients (78.6%) experienced any TRAE. The most common TRAEs of any grade were anemia, chills, eosinophilia, fatigue, fever, and rash. There was one DLT, a grade 3 bowel perforation occurring at dose level 3 in a patient with diffuse peritoneal carcinomatosis; this was managed surgically, and notably, the operative findings on day 14 documented resolution of previously observed carcinomatosis and no tumor at or near the perforation site. Dose level 3 was expanded per protocol before escalation to dose level 4, and no additional perforations occurred. The MTD and RP2D were not reached. No grade 4 or 5 TRAEs were recorded.

References

1. Clark HD, Aghlara-Fotovat S, Schladenhauffen J, et al. First-in-human trial of encapsulated cells constitutively expressing localized IL-2 in patients with high-grade serous ovarian carcinoma. Clin Cancer Res. 2026. doi:10.1158/1078-0432.CCR-25-4142
2. A study of intraperitoneally administered AVB-001 in patients with serous adenocarcinoma of the ovary. Clinicaltrials.gov. April 24, 2024. Accessed May 14, 2026. https://clinicaltrials.gov/study/NCT05538624