MB-105 / Fortress - LARVOL DELTA

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for the Treatment of Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Nov 2026 ➔ Nov 2028 | Trial primary completion date: Nov 2026 ➔ Nov 2028

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

Combining Radiopharmaceutical Therapy with CAR T cells to Overcome the Heterogeneous Immunosuppressive Prostate Tumor Microenvironment (SITC 2025) - P1 | "In a phase 1 clinical trial (NCT03873805) evaluating CAR-T cells targeting Prostate Stem Cell Antigen (PSCA), we observed promising safety and therapeutic responses in patients who underwent cyclophosphamide (Cy) lymphodepletion, but the several challenge must be addressed to improve overall responses: 1) antigen heterogeneity, and 2) the immunosuppressive tumor microenvironment (TME).2 Preclinical evidence suggests radiation enhances CAR T cell efficacy by priming the TME,3 4 yet focal radiation lacks the capability to target multi-metastatic disease systemically. The combination was well tolerated in the syngeneic mouse model, with favorable TME changes, enhanced therapeutic responses, and extended durability. By using the two therapies (177Lu-PSMA-617 and PSCA-CAR T cells) that are FDA approved or in clinical development, we aim for rapid translation of this combination strategy to patients with mCRPC and other advanced lethal cancer types."

Biomarker • CAR T-Cell Therapy • Heterogeneity • Tumor microenvironment • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • PSCA

Optimization of Safe and Effective PSCA-CAR/IL12 Engineered T cell Combinatorial Treatment Strategies Against Metastatic Prostate Cancer (PCF 2025) - "Mice were treated with PSCA-CAR/aPDL1-IL12, PSCA-CAR/mbIL12, or conventional PSCA-CAR T cells, with or without cyclophosphamide (Cy) preconditioning. The addition of fludarabine (Flu) to Cy was tested to evaluate synergistic conditioning effects...Funding Acknowledgements PCF Young Investigator Award 2021 (PI: Murad), PCF Tactical Award (PI: Pricman), Department of Defence Idea/Expansion Awards (PI: Priceman), Tower Cancer Research Foundation Career Development Award 2025 (PI: Murad) Conflict of Interest Statement There are no conflicts to report for data presented. INTERNAL"

Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IL12A • KRAS • PSCA • PTEN

Comparative efficacy and safety of PSCA CAR-engineered Vδ1 γδ T cells for immunotherapy of pancreatic cancer. (PubMed, J Immunother Cancer) - "PSCA CAR-Vδ1 γδ T cells represent a potent and safe therapeutic modality for PSCA+ PC, with efficacy comparable to other CAR T cell types and potential advantages in safety and persistence. These findings support further development of CAR-Vδ1 T cell immunotherapy for solid tumors."

Clinical • Journal • Graft versus Host Disease • Immunology • Oncology • Pancreatic Cancer • Solid Tumor • PSCA

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: May 2025 ➔ Apr 2026

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

Off-the-shelf invariant NKT cells expressing anti-PSCA CAR and IL-15 promote pancreatic cancer regression in mice. (PubMed, J Clin Invest) - "In multiple in vitro and in vivo PDAC models, freshly manufactured PSCA CAR_sIL-15 iNKT cells and frozen-thawed, off-the-shelf PSCA CAR_sIL-15 iNKT cells demonstrate comparable efficacies, and both show remarkable suppression of PSCA-positive and gemcitabine-resistant PDAC. Importantly, off-the-shelf cryopreserved PSCA CAR_sIL-15 iNKT cells show equivalent efficacy when compared with PSCA CAR T cells using the same PSCA CAR and in the same PDAC model; however, PSCA CAR_sIL-15 iNKT cells do not appear to induce systemic toxicity or graft-versus-host disease, thus allowing for multiple infusions to control recurrent disease. Collectively, our study suggests that PSCA CAR_sIL-15 iNKT cells merit clinical investigation for PDAC patients exhibiting positive PSCA expression. The therapy could be given as a single agent or in combination with established therapeutic modalities for PDAC."

Journal • Preclinical • Graft versus Host Disease • Hepatology • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • IL15 • PSCA

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ May 2025

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for the Treatment of Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jul 2028 ➔ Nov 2026 | Trial primary completion date: Aug 2027 ➔ Nov 2026

CAR T-Cell Therapy • Metastases • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

Prostate Cancer Foundation-Funded Research Shows Promising Results Against Lethal Form of Prostate Cancer (Prostate Cancer Foundation) - P1 | N=14 | NCT03873805 | "A team of investigators at City of Hope funded by the Prostate Cancer Foundation (PCF) reports that patients with advanced prostate cancer can be safely treated with chimeric antigen receptor (CAR) T cell therapy. The results of their first-in-human phase 1 clinical trial, which also showed promising therapeutic activity, were published today in Nature Medicine...The phase 1 trial treated 14 PSCA-positive patients with mCRPC which had spread beyond the prostate and no longer responded to hormone treatment, using the PSCA-directed CAR T-cell therapy...One patient’s PSA level decreased by 95% and the cancer that had spread to his bones and soft tissue also declined. He experienced this positive response for approximately eight months....The City of Hope trial is currently enrolling patients."

Enrollment status • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A phase 1b study of PSCA CAR T cells plus or minus radiation for the treatment of patients with PSCA+ metastatic castration-resistant prostate cancer. (ASCO 2024) - P1 | "Key inclusion criteria are a diagnosis of mCRPC with evaluable disease, at least one area of metastasis amenable for radiation (for the MDRT cohort), PSCA expression by immunohistochemistry on archival tissue, and prior progression on abiraterone or enzalutamide or both; prior taxane chemotherapy is allowed. The results will be used to identify the optimal strategy to move to phase 2. The study is currently open to enrollment."

CAR T-Cell Therapy • Clinical • Metastases • P1 data • Gene Therapies • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial. (PubMed, Nat Med) - P1 | "These results support future clinical studies to optimize dosing and combination strategies to improve durable therapeutic outcomes. ClinicalTrials.gov identifier NCT03873805 ."

CAR T-Cell Therapy • Journal • Metastases • P1 data • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Mar 2024 ➔ Dec 2024

CAR T-Cell Therapy • Metastases • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer. (PubMed, Cell Stem Cell) - "We optimized the cryopreservation of CAR-iMac progenitors that remain functional upon thawing, providing an off-the-shelf, allogeneic cell product that can be developed into CAR-iMacs. Overall, our preclinical data strongly support the potential clinical translation of this human iPSC-derived platform for solid tumors, including pancreatic cancer."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • EGFR • PSCA

Microbiome modification impacts PSCA directed chimeric antigen receptor (CAR) T cell therapy for prostate cancer (AACR 2024) - "We show that our mouse prostate cancer model is sensitive microbiome modulation and can significantly impact PSCA-CAR T cell directed anti-tumor responses. Temporal WGS analysis of gut fecal matter reveal enrichment suggest specific species abundances which may promote gut homeostasis over dysbiosis or inflammatory states and may account for improved CAR T cell response. We aim to further develop this model to interrogate candidate targeted microbiome modifiers which may impact mechanisms which promote CAR T cell and immune function."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2023 ➔ Mar 2024

CAR T-Cell Therapy • Metastases • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for the Treatment of Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Nov 2025 ➔ Jul 2028 | Trial primary completion date: Nov 2025 ➔ Aug 2027

CAR T-Cell Therapy • Metastases • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for the Treatment of Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: City of Hope Medical Center | Phase classification: P1b ➔ P1 | Trial completion date: Feb 2026 ➔ Nov 2025 | Trial primary completion date: Feb 2026 ➔ Nov 2025

CAR T-Cell Therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for the Treatment of Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1b | N=21 | Recruiting | Sponsor: City of Hope Medical Center | Initiation date: Jul 2023 ➔ Oct 2023

CAR T-Cell Therapy • Metastases • Trial initiation date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial primary completion date: Nov 2023 ➔ Aug 2022

CAR T-Cell Therapy • Metastases • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IFNG • IL10 • IL2 • IL6 • PSCA • TNFA

PSCA-Targeted CAR T-Cell Therapy Demonstrates Safety, Anticancer Activity in mCRPC (OncLive) - P1 | N=15 | NCT03873805 | "The use of prostate stem cell antigen (PSCA)–targeted CAR T-cell therapy was well tolerated and produced evidence of anticancer effects in patients with metastatic castration-resistant prostate cancer (mCRPC), according to final data from a phase 1 study...presented at the 2023 ASCO Annual Meeting....Among 14 evaluable patients, grade 3 cystitis was a dose-limiting toxicity (DLT) experienced by 2 of 6 patients treated with PSCA CAR T cells plus standard lymphodepletion (dose level 2)....No DLTs were reported in 5 patients treated at dose level 3; however, grade 2 cystitis occurred in 1 patient....No grade 3 or higher cytokine release syndrome was reported."

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: City of Hope Medical Center | Recruiting ➔ Active, not recruiting | N=30 ➔ 15

CAR T-Cell Therapy • Enrollment change • Enrollment closed • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IFNG • IL10 • IL2 • IL6 • PSCA • TNFA

Final results from phase I study of PSCA-targeted chimeric antigen receptor (CAR) T cells in patients with metastatic castration resistant prostate cancer (mCRPC). (ASCO 2023) - P1 | "12(86%) had previously been treated with chemotherapy; 9 received two taxanes and 3 docetaxel only...The protocol was amended to reduce the LD dose to 300 mg/m2 cyclophosphamide D1-3... PSCA-CAR T cells have anti-cancer activity in mCRPC with DLT of cystitis. LD was required for greater expansion and activity; lower dose LD improved toxicity without clear negative impact on expansion. Clinical trial information: NCT03873805."

Clinical • Metastases • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs • PSCA

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for the Treatment of Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1b | N=21 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2023 ➔ May 2023

CAR T-Cell Therapy • Enrollment open • Metastases • Trial initiation date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PSCA

Mustang Bio Announces Strategic Manufacturing Partnership and Portfolio Updates (GlobeNewswire) - "Mustang will discontinue development of its MB-102, its CD123-targeted CAR T cell therapy, as well as its HER2-, CS1- and PSCA-targeted CAR T cell therapy programs, comprising a portion of the Company’s portfolio of CAR T cell therapies being developed by the Company in partnership with City of Hope."

Discontinued • Acute Myelogenous Leukemia • Bladder Cancer • Brain Cancer • Breast Cancer • CNS Tumor • Gastric Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Leukemia • Multiple Myeloma • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Urothelial Cancer

Focal Radiotherapy Improves the Efficacy of CAR T Cells Directed Against Prostate Cancer (ASGCT 2023) - "As such, our group recently found that pre-conditioning with lymphodepleting agent, cyclophosphamide (Cy), modulates the TME to become less hostile and enhances the recruitment and activity of endogenous and CAR T cells targeting the human prostate stem cell antigen (hPSCA) against mouse prostate cancer. Cured mice who were rechallenged with wild-type antigen-negative tumors also demonstrated the longest delay in tumor out-growth compared to other initially cured mice treated without RT, indicating that the RT, Cy, and PSCA-CAR T cell treatments induced the strongest protective immune response. Our studies show that our focal RT combination treatment strategies enhance the anti-tumor activity of CAR T cells and may contribute to a more robust systemic immune response against metastatic burden in prostate cancer."

CAR T-Cell Therapy • Clinical • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Immune Modulation • Oncology • Prostate Cancer • Solid Tumor • PSCA