Abstract CT127: Phase I adoptive cellular therapy trial with actively personalized, multi-targeted CD8+ T-cells in patients with relapsed and/or refractory solid cancers (ACTologIMA101-101)
Authors: Ma Hong , Kuttruff Sabrina , Stewart Chad , Bulliard Yannick , Stephens Geoffrey , Schoor Oliver , Satelli Arun , Hilf Norbert , Sieger Kerry , Fritsche Jens , Maurer Dominik , Mohamed Ali , Weinschenk Toni , Reinhardt Carsten , Walter Steffen , Singh Harpreet , Hwu Patrick , Yee Cassian , Andersson Borje , Tsimberidou Apostolia-Marie 
Published: August 2018

Introduction:

Adoptive cellular therapy (ACT), which includes the administration of autologous or allogenic anti-tumor T lymphocytes after ex vivo manipulation and expansion, has demonstrated substantial clinical benefit in some hematological cancer types. Particularly for solid cancers, only a relatively small proportion of patients has benefited from these advances due in part to i) lack of suitable immunotherapy targets with high specificity in solid cancers and ii) frequent relapse following immunotherapy to single targets often associated with loss of target expression in the tumor.

The actively personalized IMA101 (ACTolog®) process, utilizing autologous antigen-specific T cells to multiple selected tumor targets, is intended to address these limitations. IMA101-101 is a first-in-human clinical trial in patients, with relapsed or refractory solid cancers, whose tumors express at least one target from a pre-defined warehouse of 8 cancer-specific targets. These targets were identified using Immatics' mass spectrometry (MS)-guided XPRESIDENT technology, and carefully selected for their highly tumor-associated expression profile. As such, ACTolog is a multi-target approach where up to four products with four different tumor-specificities will be infused per patient.

Methods:

One key defining feature of the approach used in this trial is the generation of robust T cells following a proprietary process, where autologous T cells are specifically primed against the expressed ACTolog targets in the presence of IL-21 followed by HLA tetramer-guided cell sorting and rapid expansion. This process has been shown to result in T-cell products with higher frequencies of central memory T cells, extended in vivo persistence and clinical response1,2. Patients are enrolled depending on their HLA-A*02:01 positivity and the expression of warehouse target(s) in the tumor. As the patients participating in this trial have a high unmet medical need (e.g. very poor prognosis and/or refractory or recurrent disease following multiple lines of therapy), treatment with IMA101 T cell products will take place when patients experience recurrence or progressive disease or when therapy is no longer warranted. It is planned that the first-in-human trial will enroll up to 20 patients.

Results:

Initial data from the patients enrolled in this ongoing Phase 1 clinical trial will be presented at the meeting with a focus on feasibility, safety, and T cell persistence and functionality.

Conclusions:

The actively personalized ACTolog® approach is unique in that it addresses the scarcity of suitable tumor antigens by using novel tumor targets identified via the MS-guided XPRESIDENT® technology. In addition, it is a multi-target approach intended to generate broad anti-tumor activity with decreased risk of tumor relapse due to loss of target expression.

References:

1. Chapuis, AG, Desmarais, C, Emerson R, Schmit TM, Shibuya K, Lai, I, Wagener F, Chou J, Roberts IM, Coffey DG, Warren E, Robbins H, Greenberg PD, Yee C (2017). "Tracking the fate and origin of clinically relevant adoptively transferred CD8+ T cells in vivo." Science Immunology 2(9)

2. Yee C. “The use of endogenous T cells for adoptive transfer.” Immunol Rev. Jan;257(1):250-63. 2014

Citation Format: Hong Ma, Sabrina Kuttruff, Chad Stewart, Yannick Bulliard, Geoffrey Stephens, Oliver Schoor, Arun Satelli, Norbert Hilf, Kerry Sieger, Jens Fritsche, Dominik Maurer, Ali Mohamed, Toni Weinschenk, Carsten Reinhardt, Steffen Walter, Harpreet Singh, Patrick Hwu, Cassian Yee, Borje Andersson, Apostolia-Marie Tsimberidou. Phase I adoptive cellular therapy trial with actively personalized, multi-targeted CD8+ T-cells in patients with relapsed and/or refractory solid cancers (ACTologIMA101-101) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT127.