BPX-601 / Bellicum - LARVOL DELTA

Early results from a phase 1, multicenter trial of PSCA-specific GoCAR T cells (BPX-601) in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2023) - P1/2 | "BPX-601, a PSCA-directed GoCAR-T cell product, has preliminary evidence of biologic activity with toxicity characteristic of previously reported CAR-T studies. Markers of rimiducid-induced GoCAR-T cell activation and proliferation were observed. Exploration of escalating weekly rimiducid doses > 0.4 mg/kg and BPX-601 cell doses is planned."

CAR T-Cell Therapy • Clinical • IO biomarker • Metastases • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CCL4 • CD40 • CSF2 • CX3CL1 • IFNG • IL18 • IL1R1 • IL6R • MYD88 • PSCA

A Phase 1 Study of BPX-601 CAR T-Cell Therapy in Adult Participants With Prostate Cancer That Has Returned, is Resistant to Treatment and Has Spread (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Phase 1 Study of BPX-601 CAR T-Cell Therapy in Adult Participants With Prostate Cancer That Has Returned, is Resistant to Treatment and Has Spread (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Nov 2030 ➔ Mar 2031

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

A Phase 1 Study of BPX-601 CAR T-Cell Therapy in Adult Participants With Prostate Cancer That Has Returned, is Resistant to Treatment and Has Spread (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P1 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Safety and Activity Study of PSCA-Targeted CAR-T Cells (BPX-601) in Subjects With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=52 | Terminated | Sponsor: Regeneron Pharmaceuticals | Phase classification: P1/2 ➔ P1 | N=151 ➔ 52 | Suspended ➔ Terminated; Due to a Dose Limiting Toxicity.

Enrollment change • Phase classification • Trial termination • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial. (PubMed, Nat Commun) - P1/2 | "Rimiducid increased circulating inflammatory cytokines/chemokines consistent with GoCAR-T® cell activation. These results suggest that pharmacological activation of GoCAR-T® cells is feasible and may offer a promising avenue to control chimeric antigen receptor-T cell activity with continued dose-optimization to improve tolerability."

Journal • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • CD40 • MYD88 • PSCA

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial (Nat Commun, Nature) - P1/2 | N=151 | NCT02744287 | Sponsor: Bellicum Pharmaceuticals | "Thirty-three patients received BPX-601 with or without rimiducid, 24 patients with mPDAC and 9 with mCRPC. Two dose-limiting toxicities and two treatment-related deaths occurred in the highest-dose mCRPC cohort, after which the study was terminated, without determination of the RP2D. Two mCRPC patients experienced partial responses (one unconfirmed), and 56% of mCRPC patients achieved ≥50% reduction in prostate-specific antigen. BPX-601 cell expansion, long-term persistence in peripheral blood, and tumor infiltration were observed."

P1 data • Castration-Resistant Prostate Cancer • Pancreatic Ductal Adenocarcinoma

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial (Nat Commun, Nature) - P1/2 | N=151 | NCT02744287 | Sponsor: Bellicum Pharmaceuticals | "Thirty-three patients received BPX-601 with or without rimiducid, 24 patients with mPDAC and 9 with mCRPC. Two dose-limiting toxicities and two treatment-related deaths occurred in the highest-dose mCRPC cohort, after which the study was terminated, without determination of the RP2D. Two mCRPC patients experienced partial responses (one unconfirmed), and 56% of mCRPC patients achieved ≥50% reduction in prostate-specific antigen. BPX-601 cell expansion, long-term persistence in peripheral blood, and tumor infiltration were observed."

P1 data • Castration-Resistant Prostate Cancer • Pancreatic Ductal Adenocarcinoma

Novel agents and clinical trials in castration-resistant prostate cancer: latest updates from 2023 ASCO-GU Cancers Symposium. (PubMed, Exp Hematol Oncol) - "Notably, radionuclide drug conjugates (RDC), specifically 177Lu/111In-J591 and 225Ac-J591, exhibited enhanced therapeutic efficacy in treating patients with CRPC. Furthermore, promising treatment approaches for CRPC included dual anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) blockade in rare tumors (DART)-Lorigerlimab, prostate stem cell antigen (PSCA)-directed chimeric antigen receptor (CAR)-T cell immunotherapy-BPX-601, and protein kinase inhibitor (AKTi)-CAPltello-280. We have summarized the latest CRPC treatment strategies presented at the 2023 ASCO-GU Cancers Symposium, along with recent advances in CRPC clinical trials."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTLA4 • PSCA

Safety and Activity Study of PSCA-Targeted CAR-T Cells (BPX-601) in Subjects With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=151 | Suspended | Sponsor: Bellicum Pharmaceuticals | Recruiting ➔ Suspended

CAR T-Cell Therapy • Metastases • Trial suspension • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Bellicum Discontinues Phase 1/2 Trials and Initiates Evaluation of Strategic Alternatives (GlobeNewswire) - "Bellicum Pharmaceuticals...announced its decision to discontinue its ongoing Phase 1/2 clinical trials evaluating the safety and preliminary efficacy of its GoCAR-T cell product candidates in combination with rimiducid in heavily pre-treated cancer patients. The trials for BPX-601 and BPX-603 are being discontinued following the Company’s assessment of the risk/benefit profile of BPX-601 in combination with rimiducid. The most recent patient treated in the Phase 1/2 trial of BPX-601 in metastatic castration-resistant prostate cancer (mCRPC) experienced serious immune-mediated adverse events including Grade 4 cytokine release syndrome (CRS), the second dose-limiting toxicity observed in this cohort of dose escalation....The Company is communicating with clinical trial sites and regulatory agencies regarding its decision to discontinue its trials, and an evaluation of the Company’s strategic alternatives is underway."

Trial termination • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Prostate Cancer • Solid Tumor

Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results from a dose escalation. (ASCO-GI 2019) - P1/2; "...BPX601 is an autologous, T-cell product engineered to contain a PSCA-CD3ζ CAR plus the small molecule rimiducid (Rim)-inducible MyD88/CD40 costimulatory domain... Patients received only cyclophosphamide (CTX) for lymphodepletion (LD) within three days before BPX601 infusion... BPX601 with single-dose Rim was well-tolerated and resulted in enhanced T cell expansion and prolonged persistence in some patients despite lack of LD. Evidence of clinical benefit in this heavily pretreated mPDAC population was seen. Part 2 is planned to open soon and will include CTX/fludarabine LD to maximize engraftment as well as gastric and prostate cancers."

CAR T-Cell Therapy • IO Biomarker

Bellicum Presents Early Phase 1 Results for BPX-601 in Prostate Cancer at ASCO GU Cancers Symposium (GlobeNewswire) - P1/2 | N=181 | NCT02744287 | Sponsor: Bellicum Pharmaceuticals | "Bellicum Pharmaceuticals, Inc...will present early Phase 1 results for BPX-601 at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in San Francisco and virtually....Four of eight (50%) patients achieved a PSA50 response, three of whom achieved a PSA90 response. Of the six patients with soft tissue (visceral and/or lymph node) disease, two achieved partial responses by RECIST v1.1, one of which was confirmed. Of the two patients with bone-only disease, one patient achieved a PSA90 response with decreased enhancement of bone lesions observed on bone scan."

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

Bellicum Pharmaceuticals to Present Early Phase 1 Results for BPX-601 in Prostate Cancer at ASCO 2023 Genitourinary Cancers Symposium (GlobeNewswire) - "Bellicum Pharmaceuticals...announced that an abstract on early results from a Phase 1 clinical trial for BPX-601, its lead GoCAR-T® product candidate, has been accepted for poster presentation at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU). The meeting is being held February 16-18, 2023 in San Francisco and virtually. The ongoing trial is being conducted in patients with metastatic castration-resistant prostate cancer."

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

Safety and Activity Study of PSCA-Targeted CAR-T Cells (BPX-601) in Subjects With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=151 | Recruiting | Sponsor: Bellicum Pharmaceuticals | Trial completion date: Feb 2024 ➔ Feb 2026 | Trial primary completion date: Oct 2022 ➔ Oct 2025

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Bellicum Reports Fourth Quarter 2021 Financial Results and Provides Operational Update (GlobeNewswire) - "Enrollment in the Phase 1/2 dose escalation clinical trial in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC) is ongoing....The company expects to present a data update on BPX-601 in the first quarter of 2023....Enrollment is ongoing in the Phase 1/2 clinical trial for BPX-603 in patients with solid tumors that express human epidermal growth factor 2 (HER2), including breast, endometrial, ovarian, gastric, and colorectal cancers....The company expects to present a data update on BPX-603 in the first half of 2023."

Enrollment status • P1/2 data • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Urothelial Cancer • Uterine Cancer

Bellicum Announces Positive Interim Data from Phase 1/2 GoCAR-T Studies, Secures $35 Million Private Placement Equity Financing Priced at Market (GlobeNewswire) - P1/2, N=151; NCT02744287; Sponsor: Bellicum Pharmaceuticals; "Cell dose escalation and optimization of the lymphodepletion regimen was completed in the Phase 1/2 clinical trial of BPX-601 in metastatic pancreatic cancer patients...No dose-limiting toxicities were observed. Adverse events were comparable to those previously seen with BPX-601 and rimiducid in metastatic pancreatic cancer and typical of other cell therapy regimens...Enrollment is ongoing in the second dose cohort in mCRPC of 5x106 cells/kg followed by weekly rimiducid, and results from these patients will be submitted for presentation at a medical meeting in 2022."

Trial status • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer

Bellicum Announces Positive Interim Data from Phase 1/2 GoCAR-T Studies, Secures $35 Million Private Placement Equity Financing Priced at Market (GlobeNewswire) - "Bellicum has also entered into an agreement for a $35 million private placement of equity securities with two biotechnology specialist investment funds. Proceeds from the financing will be used to support ongoing clinical development of BPX-601 and BPX-603."

Licensing / partnership • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Positive Breast Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Solid Tumor

Bellicum Reports Third Quarter 2021 Financial Results and Provides Operational Update (Bellicum Press Release) - "BPX-601 GoCAR-T: Enrollment in the Phase 1/2 dose escalation clinical trial in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC) is ongoing. Bellicum expects to announce the first interim data in mCRPC in the first quarter of 2022....BPX-603 GoCAR-T: The company expects to announce initial Phase 1 data from this trial in the fourth quarter of 2021."

Enrollment status • P1 data • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Tumor infiltration and cytokine biomarkers of prostate stem cell antigen (PSCA)-directed GOCAR-T cells in patients with advanced pancreatic tumors. (ASCO-GI 2020) - P1/2; "BPX-601 is an autologous GOCAR-T cell therapy engineered to express a PSCA-CD3ζ CAR and the MyD88/CD40 (iMC) costimulatory domain activated by rimiducid (Rim), designed to boost CAR-T performance in solid tumors. BPX-601 GOCAR-T cells expand and persist in patients with PSCA+ metastatic pancreatic cancer and infiltrate metastatic lesions. A peripheral cytokine signature was observed following BPX-601 infusion. Select cytokines were enhanced after GOCAR-T cell activation and may correlate with clinical response."

Biomarker • CAR T-Cell Therapy • Clinical • IO biomarker • Gastrointestinal Cancer • Pancreatic Cancer • Solid Tumor • CD40 • CSF2 • IFNG

Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results from a dose escalation. (ASCO-GI 2019) - P1/2; "...BPX601 is an autologous, T-cell product engineered to contain a PSCA-CD3ζ CAR plus the small molecule rimiducid (Rim)-inducible MyD88/CD40 costimulatory domain... Patients received only cyclophosphamide (CTX) for lymphodepletion (LD) within three days before BPX601 infusion... BPX601 with single-dose Rim was well-tolerated and resulted in enhanced T cell expansion and prolonged persistence in some patients despite lack of LD. Evidence of clinical benefit in this heavily pretreated mPDAC population was seen. Part 2 is planned to open soon and will include CTX/fludarabine LD to maximize engraftment as well as gastric and prostate cancers."

CAR T-Cell Therapy • IO biomarker • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor

Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results from a dose escalation study (ESMO-IO 2018) - P1/2; "...BPX601 is an autologous, T-cell product engineered to contain a PSCA-CD3 CAR plus the small molecule rimiducid (Rim)-inducible MyD88/CD40 costimulatory domain...Results Patients received only cyclophosphamide (CTX) for lymphodepletion (LD) within 3 days before BPX601 infusion...Evidence of clinical benefit in this heavily pretreated mPDAC population was seen. Part 2 is planned to open soon & will include CTX/fludarabine LD to maximize engraftment as well as gastric & prostate cancers."

CAR T-Cell Therapy • IO biomarker • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor

Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results with cyclophosphamide (Cy) fludarabine (Flu) lymphodepletion (LD). (ASCO 2019) - P1/2; "BPX-601, an autologous T-cell product expressing a PSCA-CD3ζ CAR and a rimiducid (Rim)-inducible MyD88/CD40 co-activation switch to augment T-cell proliferation and persistence, is designed to have enhanced efficacy in solid tumors vs traditional CARs. BPX-601+Rim was well-tolerated with manageable safety and early evidence of enhanced CAR T-cell expansion and prolonged persistence after Flu/Cy vs Cy. Additional pts will undergo Flu/Cy LD prior to BPX-601 with single- and repeat-dose Rim. Clinical trial information: NCT02744287"

CAR T-Cell Therapy • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Bellicum Reports Second Quarter 2021 Financial Results and Provides Operational Update (GlobeNewswire) - "Bellicum expects to provide a Phase 1 data update on BPX-601 and rimiducid in patients with mCRPC in the first quarter of 2022...BPX-603 is the company’s first dual-switch GoCAR-T product candidate, which incorporates Bellicum’s iMC activation and CaspaCIDe® safety switch technologies. The company expects to present initial Phase 1 data from this trial in the fourth quarter of 2021."

P1 data • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

Bellicum Reports Fourth Quarter 2020 Financial Results and Provides Operational Update (GlobeNewswire) - "Bellicum plans to present a Phase 1 data update on BPX-601 and rimiducid in patients with metastatic castration-resistant prostate cancer in the first quarter of 2022...The company expects to provide initial Phase 1 data from...Phase 1/2 clinical trial for BPX-603 in patients with solid tumors that express human epidermal growth factor 2 (HER2), including breast, endometrial, ovarian, gastric, and colorectal cancers...in the second half of 2021."

P1 data • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor