(UroToday.com) The 2022 GU ASCO Annual meeting included a prostate cancer session highlighting work from Dr. Tanya B. Dorff and colleagues presenting results of their phase 1 study assessing PSCA-targeted CAR T cell therapy for mCRPC. CAR-engineered T cell therapies are being pursued for the treatment of mCRPC. Prostate Stem Cell Antigen (PSCA) is highly expressed on the surface membrane in mCRPC and with limited expression on normal tissues. Dr. Dorff and investigators undertook a phase 1, first-in-human study of a PSCA-targeted 4-1BB-co-stimulated CAR T cell therapy in mCRPC.
CAR T cells were manufactured at City of Hope’s cGMP facility. The trial followed the Target equivalence range design with an equivalence range of 0.20-0.35 and too toxic level of 0.51 following participants in cohorts of 3. The plan was to begin at a dose of 100 million (M) without lymphodepletion (LD) chemotherapy consisting of fludarabine and cyclophosphamide, then add LD to 100M prior to dose escalation to maximum 600M. The full treatment schedule for this phase 1 trial is as follows:
Patients were required to have disease progression after at least 1 androgen receptor targeted therapy but there was no limit on prior chemotherapy or other treatments. The primary objective is to define the dose limiting toxicity and recommended phase 2 dose as well as to describe preliminary bioactivity and efficacy. Correlative studies include MRI for target bone lesion response, CAR T cell persistence, circulating tumor cells, and serum cytokines.
There have been 12 patients treated to date, with a median age 68 (range: 42-72). Three patients were treated at the 100M dose with no dose limiting toxicities. In the 100M plus LD dose level there were 2 patients that experienced dose limiting toxicity of grade 3 cystitis non-infective and fatigue. The protocol was amended to reduce the LD dose to 300 mg/m2 cyclophosphamide D1-3 and intensify monitoring with early intervention for cystitis. No dose limiting toxicity occurred in 3 patients treated in the modified LD 100M cohort. Cytokine release syndrome (CRS), dose limiting toxicities and best response by RECIST are presented by dose level as follows:
PSA declines (one >90%) were seen as well as radiographic improvement, though RECIST response was limited to stable disease (SD) by concurrent bone metastases:
One patient with PSA decline, bone-only disease, stable for months after the first dose, received a second infusion. Additionally, one patient in the modified LD chemotherapy group had radiographic improvement.
Dr. Dorff concluded this presentation of PSCA-targeted CAR T cell therapy for mCRPC with the following take-home points:
- PSCA-CAR T cell therapy is feasible in patients with mCRPC
- There was dose limiting toxicity of cystitis (likely due to PSCA expression in the bladder)
- Preliminary responses are promising and a phase 1b trial in preparation to further optimize efficacy and to minimize toxicity
Presented by: Tanya B. Dorff, City of Hope Comprehensive Cancer Center, Duarte, CA
Co-Authors: Suzette Blanchard, Hripsime Martirosyan, Lauren Adkins, Gaurav Dhapola, Aidan Moriarty, Jamie R Wagner, Ammar Chaudhry, Massimo D'Apuzzo, Peter Kuhn, Stephen J. Forman, Saul Priceman
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022