Memory T Cell CAR T Therapy Showcases Anti-Tumor Activity in Resistant Prostate Cancer
Interim data from the SPOTLIGHT study were presented at the ASCO GU Symposium.
P-PSMA-101, Poseida Therapeutics’ autologous chimeric antigen receptor (CAR) T-cell candidate, has shown promising anti-tumor activity in metastatic castration-resistant prostate cancer (mCRPC), with significant declines in prostate-specific antigen recorded.1,2
Data from the phase 1 SPOTLIGHT trial (NCT04249947) were presented at ASCO Genitourinary Cancers Symposium (ASCO GU), February 17-22, in San Francisco, California, by investigator Susan F. Slovin, MD, PhD, of Memorial Sloan Kettering Cancer Center.
"The results being presented at ASCO GU continue to reinforce the potential for a CAR-T product to effectively treat solid tumor indications like prostate cancer," said Mark Gergen, Chief Executive Officer of Poseida Therapeutics, in a statement.1 "We are excited by the initial responses seen even at the lowest doses and will continue to evaluate additional dosing regimens as we treat patients. We are also encouraged by the durable responses observed to date and look forward providing additional updates on this program as the trial progresses."
The SPOTLIGHT trial is assessing P-PSMA-101, which is an autologous CAR-T therapy targeting PSMA and includes a high percentage of stem cell memory T cells (TSCM).2 The therapy is developed using the novel piggyBac non-viral transposon system that creates high TSCM products.
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The open-label, multi-center, dose-escalation, phase 1 trial has treated 17 participants of an expected 60 in 3 cohorts so far, 14 of which were evaluable as of the cutoff date in December 2021. Participants were treated with 0.25X106 cells/kg (n = 6), 0.75X106 cells/kg (n = 7), or 2.0X106 cells/kg (n = 1) after lymphodepletion regimens of fludarabine and cyclophosphamide. Participants had an average of 7 prior lines of therapy and a median 6.4 years since diagnosis.
Investigators assessed efficacy via Prostate Cancer Working Group 3 (PCWG3) criteria including prostate-specific antigen (PSA), bone scans/CT, and exploratory biomarkers and novel tumor-targeted PET imaging (PSgMA-PET, FDG). They found measurable PSA declines in 10 patients (71%), 5 of whom (36%) had declines of at least 50%. One patient exhibited complete tumor elimination which has remained durable for over 10 months. TSCM helped CAR T-cell cells traffic to the bone, as seen in clinical evidence and confirmed by biopsy.
The therapy has so far demonstrated an acceptable safety profile. Treatment-related adverse events (AEs) did occur; these included cytokine release syndrome (grade 1/2, n = 6; ≥ grade 3, n = 2) macrophage activation syndrome (n = 1), and immune effector cell-associated neurotoxicity syndrome (n = 2). Other common AEs included fatigue, chills, headache, and blurred vision.
"The responses we have seen in this trial are impressive and speak to the innovative nature and potential of Poseida's CAR-T cell therapy platform," Slovin added to the statement.1 "This interim update on the P-PSMA-101 trial shows the exceptional efficacy of this novel anti-PSMA CAR-T cell product. Thus far, at very low doses P-PSMA-101 has shown to produce a robust and durable anti-tumor response in heavily pretreated patients with mCRPC, including one pathologic complete response."
