Abstract CT011: A phase 1 multicenter study (TRAVERSE) evaluating the safety and efficacy of ALLO-316 following conditioning regimen in pts with advanced or metastatic clear cell renal cell carcinoma (ccRCC)
Authors: Srour Samer , Kotecha Ritesh , Curti Brendan , Chahoud Jad , Drakaki Alexandra , Tang Lily , Goyal Lovely , Prashad Sacha , Szenes Victoria , Norwood Kevin , Pal Sumanta 
Published: April 2023

Abstract
Background: While doublet therapies provide important first-line treatment options in metastatic renal cell carcinoma (mRCC), novel and mechanistically distinct agents are needed for pts who are not cured by/intolerant of such therapies. Due to the high incidence (~80%) of CD70 antigen expression in primary and mRCC, yet limited expression in normal tissue, ccRCC is an attractive proof-of-concept tumor for CD70 directed allogeneic CAR T. TRAVERSE (NCT04696731), a first-in-human trial, seeks to identify a maximum tolerated dose (MTD) of ALLO-316 after conditioning with fludarabine/cyclophosphamide with/without ALLO-647 in pts with advanced or metastatic ccRCC. ALLO-316 is an anti-CD70 allogeneic CAR T cell product that utilizes TALEN® gene editing to knock out TCRα constant gene to reduce the risk of graft-versus-host disease (GvHD) and knock out CD52 gene to permit use of ALLO-647 (a humanized anti-CD52 mAb) to selectively deplete host T cells without affecting allogeneic CAR T cells.
Methods: This multicenter, single-arm, open-label, 3+3 dose-escalation trial enrolls adults with advanced or metastatic ccRCC and ≥1 measurable lesion and ECOG Performance Status 0 or 1. Prior treatment with an immune checkpoint inhibitor and a vascular endothelial growth-factor targeted therapy was required, with evidence of progression on/after treatment or discontinuation due to toxicity. ALLO-316 is administered at escalating doses (40 - 240 × 106 allogeneic CAR+ cells IV) on Day 0 after conditioning. The primary endpoint is a target incidence rate for dose-limiting toxicities (DLTs) &lt;33% in the first 28 days after infusion of ALLO-316.
Results: By 12/3/2022, 18 pts with ccRCC (median age: 63 yrs; 82% male) were enrolled; all (100%) 17 pts who received ALLO-316, had metastatic disease with 3 lines (median) of prior therapy. Eleven (65%) of these pts experienced CRS, all low Gr except one (6%) Gr 3. No ICANS or GVHD was observed. One (6%) DLT (elevated LFT) was observed and required dose expansion. MTD has not yet been reached. Three pts achieved best overall response of PR at all time points with two PRs confirmed at subsequent visits; ORR = 12% and disease control rate (DCR) = 71%. In pts with confirmed CD70+ tumors (n=9), confirmed ORR = 22% (unconfirmed ORR = 33%) and DCR = 100%. High CAR T cell expansion was observed in peripheral blood (median Cmax &gt; 35,000 copies/μg) and high VCN in available tumor aspirates (n=3).
Conclusions: ALLO-316, an allogeneic CAR T cell product targeting CD70 in advanced mRCC, is demonstrating encouraging antitumor activity and a manageable safety profile. A single administration of ALLO-316 could be an effective treatment for pts with CD70+ solid tumors, including RCC, and hematologic malignancies. The MTD for ALLO-316 in TRAVERSE will support Phase 2 trial design. Enrollment of pts with CD70+ tumors is ongoing.
Citation Format: Samer Srour, Ritesh Kotecha, Brendan Curti, Jad Chahoud, Alexandra Drakaki, Lily Tang, Lovely Goyal, Sacha Prashad, Victoria Szenes, Kevin Norwood, Sumanta Pal. A phase 1 multicenter study (TRAVERSE) evaluating the safety and efficacy of ALLO-316 following conditioning regimen in pts with advanced or metastatic clear cell renal cell carcinoma (ccRCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT011.