A phase 1/2 open-label, multicenter, dose escalation and expansion study of AVB-001, an intraperitoneally administered, cell-generated, human IL-2 immunotherapy in patients with platinum-resistant, high-grade, serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube.
Authors: Westin Shannon Neville , Yeku Oladapo O. , Sims Travis T. , Bregar Amy , Andreas Karen , Soliman Eric , Jain Manish , Dansky Ullmann Claudio , Jazaeri Amir A. 
Published: June 2023

TPS5616 Background: The potential of cytokines as cancer therapeutics has been limited by short half-life and severe adverse effects associated with high systemic exposure when delivered intravenously. Many strategies are being explored to overcome these limitations. A locoregional delivery approach to achieve high sustained local concentrations in the tumor microenvironment with minimal systemic exposure could widen the therapeutic window. Early experience with free recombinant human IL2 (rhIL-2) given intraperitoneally (IP) showed meaningful clinical activity in relapsed ovarian cancer. Still, the cumbersome delivery procedure requiring indwelling catheters and need for high volume IP infusions leading to frequent complications and poor patient compliance limited the utility of this approach. To overcome these shortcomings, we developed a clinically translatable localized delivery LOCOcyte platform composed of polymer encapsulated allogeneic epithelial cells engineered to produce immune effector molecules for local delivery with temporal regulation. The first product, AVB-001, produces native hIL-2, for the treatment of ovarian cancer and other peritoneal malignancies. IP AVB-001 inhibited tumor growth and improved survival in an in vivo ID8 ovarian cancer murine model. Sustained IL-2 production with well tolerated high IP concentrations were achieved, with >100x differential concentration vs. systemic blood levels in both mice and non-human primates. Strong local and systemic immune activating effects, optimized T cell profile and immune memory were observed without concomitant increase of T regs. The first in human study of AVB-001 in patients with advanced ovarian cancer (NCT05538624) is described here. Methods: Part 1 dose escalation exploring 4 ascending dose levels (capsules target production of 0.6, 1.2, 2.4, and 3.6 ug hIL2/kg/d) with a Bayesian Optimal Interval 3+3 design, in patients with recurrent high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube. A minimum of 12 and up to 24 patients will be enrolled to receive one dose of AVB-001 administered IP. The primary objective is to evaluate safety (Incidence and severity of adverse events per NCI CTCAE v5.0), tolerability, and feasibility of delivering AVB-001 IP, and establish the RP2D. Secondary objectives include assessment of antitumor activity (RECIST v1.1, iRECIST), pharmacokinetics, and pharmacodynamic correlates of immune activation. Part 2 will enroll 20 patients at the RP2D with efficacy as the primary objective. This multicenter study will be conducted at 5 sites, currently two sites are open. The first patient was dosed in December 2022. Recruitment in dose level 1 cohort continues. Clinical trial information: NCT05538624 .