P-BCMA-101 / Poseida Therap, J&J - LARVOL DELTA

Late Polyclonal P-BCMA-101 CAR-T Cell Re-Expansion and Rapid Complete Response in a Patient with Relapsed Multiple Myeloma Treated with One Cycle of Talquetamab, More Than 3 Years after CAR-T Infusion (ASH 2024) - "Here, we report a case of a 57-year-old female with RRMM who initially received P-BCMA-101, a TSCM rich autologous CAR-T manufactured using the piggyBac DNA delivery system, on 8/24/20 in combination with Rituximab (375 mg/m2 on days -12, -5 and then every 8 weeks for 10 cycles) and LD (cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day on days -5, -4 and -3)...She was treated with Daratumumab, Pomalidomide and dexamethasone for ~7 months with stable disease and then Selinexor and dexamethasone for 2 months which was poorly tolerated...This is the first such report of a transposon manufactured TSCM rich CAR-T showing late and dramatic re-expansion following exposure to a TCE. This case also demonstrates that T-cell proliferations following CAR-T therapy may not always be malignant and thorough molecular analysis beyond what is the clinical standard is necessary to rule out benign processes."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • T Cell Non-Hodgkin Lymphoma • B3GAT1 • CD2 • CD4 • CD5 • CD7 • CD8 • MME • NCAM1

Poseida Therapeutics to Present Clinical and Preclinical Data on Investigational Allogeneic CAR-T Cell Therapies at SITC 2024 and ASH 2024 (PRNewswire) - "Poseida Therapeutics...announced new preclinical data on allogeneic CAR+TCR-T cells rich in stem cell memory T cells (T_SCM), along with platform enhancements aimed at enhancing potency and improving targeting of solid tumors, will be presented at the Society for Immunotherapy of Cancer (SITC)...Additionally, the Company announced presentations at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition, which will be held December 7-10 in San Diego. To further characterize compelling emerging P-BCMA-ALLO1 clinical data, additional profiling of patient responses from the optimized lymphodepletion arm (Arm C) of the P-BCMA-ALLO1 Phase 1 study, along with data first presented at the 21st International Myeloma Society (IMS) Annual Meeting will be highlighted as a poster presentation. In addition, preclinical data from the ongoing Phase 1 trial of P-CD19CD20-ALLO1 in patients with B-cell malignancies will be delivered as a poster presentation."

Clinical data • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

Poseida Therapeutics Presents New Case Study Demonstrating Reactivation of CAR-T Therapy with a T-Cell Engager in a Patient with Relapsed Multiple Myeloma (PRNewswire) - P1 | N=231 | NCT04960579 | Sponsor: Poseida Therapeutics, Inc. | "Poseida Therapeutics, Inc...highlighted new data from a case study of a patient with relapsed multiple myeloma treated in a clinical trial of P-BCMA-101...The data were presented in an oral session at the Society of Hematologic Oncology (SOHO) Twelfth Annual Meeting in Houston....Two months after receiving treatment, the patient achieved a partial response that deepened into a stringent complete response and remained in remission for nearly 2 years (22.5 months). More than three years after receiving P-BCMA-101, she relapsed and was treated with one cycle of talquetamab, a T-cell engaging bispecific antibody that targets CD3 and GPRC5D....The Company will report new clinical data at the International Myeloma Society 21st Annual Meeting, which is being held in Rio de Janeiro from September 25-28, 2024. Additional P-BCMA-ALLO1 clinical updates are planned for the second half of 2024..."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Aldevron's NanoplasmidTM: A Next Generation Vector Manufacturing Platform for Gene and Cell Therapy (ASGCT 2024) - P1/2 | "• Poseida Therapeutics showed that Nanoplasmid vectors have better efficacy and equal safety in patients compared to standard plasmids when used for CAR-T production with the piggyBac® transposition (Clinical Trial NCT03288493, P BCMA-101)...Plain Language Summary: The same plasmid manufacturing technology has been used for decades in vaccination, cell and gene therapy, and as a raw material in viral vector and mRNA production. While canonical Escherichia coli plasmids contain antibiotic resistance markers and have backbones that are greater than 2000 bp, smaller backbones were shown to have reduced cell-transfection-associated toxicity and transgene silencing."

IO biomarker • Gene Therapies • Oncology

A Tumor-Bearing Murine Xenograft Model As a Bioassay for Assessing CAR-T Product Potency Shows Positive Predictive Value for Clinical Performance (ASH 2023) - P1, P1/2 | "Using these specifications, we evaluated the in vivo potency performance of GMP-manufactured Auto FP samples (P-BCMA-101; NCT03288493) generated from multiple myeloma (MM) patients and administered in the clinic with known responses ranging from poor (no response or stable disease) to significant (very good partial response [VGPR] or stringent complete response [sCR])...In the Auto CAR-T setting, this assay could be utilized for correlative studies including possible biomarker identification. In the Allo CAR-T setting, this potency bioassay may inform FP manufacturing consistency and quality for lot release to ensure patients receive only the highest quality products."

IO biomarker • Preclinical • Gene Therapies • Hematological Malignancies • Multiple Myeloma • Oncology

[VIRTUAL] BCMA-Directed CAR T-Cells: Early Results and Future Directions (SOHO 2021) - "Other Constructs of Interest Orva-cel (orvacabtagene autoleucel) is an anti-BCMA CAR T product with a construct containing a fully human scFv, an optimized spacer, a 4-1BB co-stimulatory domain, and a CD3z activation domain...Bb21217 has an identical construct to ide-cel except for coculturing with the phosphoinositide 3 kinase inhibitor (PI3K) bb007 during ex vivo culture to enrich for T cells displaying a memory-like phenotype...The ORR was 94%.17 P-BCMA-101 is a novel construct using an anti-BCMA Centyrin™ fused to a 4-1BB costimulatory domain and CD3z signaling domain...Both ide-cel and cilta-cel are being evaluated in various patient populations, including early-relapse and newly diagnosed high-risk patients...The first results of an allogeneic BCMA-directed CAR-T was with ALLO-715. The initial results from the UNIVERSAL phase 1 study in RRMM are encouraging, with responses reported and more attenuated toxicity.26 Others, including CTX120, BCMAUCART, UCART CS1, and..."

CAR T-Cell Therapy • Hematological Malignancies • Multiple Myeloma • Oncology • CD19 • CD4 • CD8 • SDC1 • TNFA

[VIRTUAL] Safety and Adverse Reactions of CAR T Therapy for the Treatment of Multiple Myeloma: A Systematic Review (ASH 2020) - "Commonly used CAR T regimens for the treatment of MM were bb2121 BCMA, P BCMA 101 CAR, LCAR B38 M, and anti CD19 CAR...JNJ-4528, bb2121 In a phase Ib/II trial, Berdeja et al...Dual Target CAR T (Table 2) Anti-CD19/BCMA, PF-3135, Dual Target BM38: In a phase Ib trial, Shi et al... CAR T therapy is emerging as a treatment modality for RRMM. With promising initial results, there is evidence for multiple side effects, the most concerning and common one is CRS. The most frequently occurring CRS grade is G 1&2 (requiring symptomatic treatment), but G3 CRS is also reported which can be dose-limiting and life-threatening."

Clinical • Review • Cardiovascular • Heart Failure • Hematological Disorders • Hematological Malignancies • Hepatology • Hypotension • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Clinical Trials of BCMA-Targeted CAR-T Cells Utilizing a Novel Non-Viral Transposon System (ASH 2021) - P1, P1/2 | "Similar P-BCMA-101 dose escalation was performed in combination cohorts with rituximab (Rit) or lenalidomide (Len)...Patients were heavily pre-treated with a median of 6 prior regimens (range 3-18), 100% had received prior PI and IMiD, 74% daratumumab and 63% ASCT...Tocilizumab was used in 11% of patients...Patients will receive P-BCMA-ALLO1 following LDC with cyclophosphamide (300 mg/m 2 /day) / fludarabine (30 mg/m 2 /day X 3 days...Allogeneic CAR-T cells generated from this platform represent a further advance. Current data from both clinical studies will be presented."

CAR T-Cell Therapy • Clinical • IO biomarker • Anemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplant Rejection • B2M • CASP9 • CD38 • DHFR • TRB

Long-Term Follow-Up Study for Subjects Treated With P-BCMA-101 (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Poseida Therapeutics, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2 | N=105 | Terminated | Sponsor: Poseida Therapeutics, Inc. | N=220 ➔ 105 | Trial completion date: Mar 2024 ➔ Apr 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2024 ➔ Apr 2022; Phase I portion of the study was completed. The phase II portion of the study was terminated early to focus on an Allogeneic BCMA CAR-T program.

CAR T-Cell Therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology • IL6

Current state and next-generation CAR-T cells in multiple myeloma. (PubMed, Blood Rev) - "Here, we review the main clinical trials of CAR-T cells in MM with the most advanced autologous BCMA-directed ide-cel and cilta-cel, the human CARs orva-cel and CT053, the alternative manufacturing process with P-BCMA-101 and bb21217, the dual CAR GC012F and the allogenic BCMA-directed CAR-T cells ALLO-715. In light of those clinical data, we provide an overview of CAR-T cells' main potential resistance mechanisms, including antigen loss, antigen spreading, anti-CAR antibodies, CAR-T cell exhaustion, and the emergence of a non-permissive microenvironment. Finally, we describe the principal area of research to build the next generation of CAR-T cells, with armored-, gated- or commuting-CARs, CARs associated with knock out of specific genes, and CAR-T cells made from γδT cells or NK cells."

CAR T-Cell Therapy • Journal • Review • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

P-BCMA-101: “P-BCMA-101, a non-viral transposon-based autologous CAR-T demonstrates is well tolerated and demonstrates strong anti-tumor activity in an advanced late line RRMM patient. It can be safely administered fully outpatient” (Poseida Therapeutics) - ASH 2021

P1/2 data • Multiple Myeloma • Oncology

P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2; N=220; Active, not recruiting; Sponsor: Poseida Therapeutics, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Jun 2022 ➔ Mar 2024; Trial primary completion date: Dec 2021 ➔ Mar 2024

CAR T-Cell Therapy • Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • IL6

[VIRTUAL] Phase 1/2 Study of the Safety and Response of P-BCMA-101 CAR-T Cells in Patients with Relapsed/Refractory (r/r) Multiple Myeloma (MM) (PRIME) with Novel Therapeutic Strategies (ASH 2020) - P1/2 | "Patients are apheresed to harvest T cells, P-BCMA-101 is then manufactured and administered to patients intravenously (IV) after a standard 3-day cyclophosphamide (300 mg/m2/day) / fludarabine (30 mg/m2/day) lymphodepletion regimen...Patients were heavily pre-treated (median of 7 prior regimens; range 3-18), with 100% having received proteasome inhibitors and IMiD, 93% daratumumab and 58% ASCT...Only 3 patients required tocilizumab and no patients required ICU admission, safety switch activation or other aggressive measures...Four patients were subsequently treated with cyclic administration, rituximab, lenalidomide or single administration at the lowest dose level with this manufacturing process (all treated with P-BCMA-101 within ~2 months prior to the data cut-off date), and thus far all have rapidly responded (100% ORR) and all responses are ongoing...In conclusion, current clinical data are consistent with preclinical findings that the novel design of..."

CAR T-Cell Therapy • Clinical • IO Biomarker • P1/2 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • IL6

Clinical trial of P-BCMA-101 T stem cell memory (Tscm) CAR-T cells in relapsed/refractory (r/r) multiple myeloma (MM) (AACR 2018) - P1; "...Patients are apheresed to harvest T cells, then P-BCMA-101 CARTyrin T cells are manufactured and administered to patients as a single dose after a standard cyclophosphamide/fludarabine conditioning regimen.Preliminary Two heavily pretreated patients are thus far evaluable at a dose of 0.75 x 106 CARTyrin+ cells / kg... Two heavily pretreated patients are thus far evaluable at a dose of 0.75 x 106 CARTyrin+ cells / kg. P-BCMA-101 manufactured for patients were primarily Tscm, and demonstrated robust and specific in vitro killing and cytokine production against BCMA+ tumor cells. Both patients MM was BCMA+."

CAR T-Cell Therapy • Clinical • IO biomarker • Multiple Myeloma

Efficacy and Safety of P-Bcma-101 CAR-T Cells in Patients with Relapsed/Refractory (r/r) Multiple Myeloma (MM) (ASH 2018) - P1; "...Patients are apheresed to harvest T cells, P-BCMA-101 is then manufactured and administered to patients as a single intravenous (IV) dose after a standard 3-day cyclophosphamide (300 mg/m2/day) / fludarabine (30 mg/m2/day) conditioning regimen...Patients were heavily pre-treated (3-9 prior therapies), 100% had failed IMiDs, proteasome inhibitors and daratumumab, and 64% had high-risk cytogenetics...No patients required treatment with tocilizumab or safety switch activation...In conclusion, current clinical trial data in patients with r/r MM support preclinical findings that the novel design of P-BCMA-101 can produce significant efficacy, comparing favorably with other anti-BCMA CAR-T products at similar doses, with notably less CRS and no neurotoxicity, consistent with the hypothesis of an improved therapeutic index. Funding by Poseida Therapeutics and CIRM."

CAR T-Cell Therapy • Clinical • IO biomarker • Biosimilar • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology

Phase 2 Study of the Response and Safety of P-Bcma-101 CAR-T Cells in Patients with Relapsed/Refractory (r/r) Multiple Myeloma (MM) (PRIME) (ASH 2019) - P1/2; "Patients are apheresed to harvest T cells, P-BCMA-101 is then manufactured and administered to patients as a single intravenous (IV) dose (6-15 x 106 P-BCMA-101 CAR-T cells/kg) after a standard 3-day cyclophosphamide (300 mg/m2/day) / fludarabine (30 mg/m2/day) conditioning regimen...With a 100-subject sample, the Phase 2 part of the trial will have 90% power to detect a 15-percentage point improvement over a 30% response rate (based on that of the recently approved anti-CD38 antibody daratumumab), using an exact test for a binomial proportion with a 1-sided 0.05 significance level...Studies are being initiated in combination with approved therapeutics and earlier lines of therapy with the intent of conducting Phase 3 trials. Funding by Poseida Therapeutics and the California Institute for Regenerative Medicine (CIRM)."

CAR T-Cell Therapy • Clinical • IO biomarker • P2 data • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Multiple Myeloma • Oncology • CD38

Dr. Shah on Unmet Needs With CAR T-Cell Therapy in Multiple Myeloma (OncLive) - "Nina Shah, MD...discusses unmet needs with CAR T-cell therapy in multiple myeloma. Although CAR T-cell therapy has been a welcome addition to the multiple myeloma landscape, the treatment isn't curing patients and no plateau has been seen on the survival curves, Shah says....Ultimately, refining the culturing, engineering, and manufacturing process of CAR T-cell therapy may improve the success of this therapeutic modality and provide prolonged responses to patients with multiple myeloma, Shah concludes."

CAR T-Cell Therapy • Video

Poseida Therapeutics Presents Preliminary Results from Phase 1 Trial of P-PSMA-101 at the 6th Annual CAR-TCR Summit (PRNewswire) - “This presentation will outline Phase 1 and 2 development of the Company's lead autologous P-BCMA-101 CAR-T therapy and insights that were used to develop a fully allogeneic version, P-BCMA-ALLO1 that is expected to enter the clinic soon….This presentation will discuss how Poseida's piggyBac® DNA Delivery System, Cas-CLOVER™ Site-specific Gene Editing System and Booster Molecule are used to manufacture multi-product, fully allogeneic T-cell therapies…This presentation will discuss leveraging the piggyBac DNA Delivery System and Cas-CLOVER Site-specific Gene Editing System to generate off-the-shelf fully allogeneic CAR-T cells to specifically target hematopoietic cells in the bone marrow.”

Clinical data • Hematological Malignancies • Multiple Myeloma • Oncology

Poseida Therapeutics Reports Program Updates and Financial Results for the Second Quarter of 2021 (PRNewswire) - "P-BCMA-101 is an autologous CAR-T product candidate currently in an ongoing Phase 1 dose expansion trial and Phase 2 trial in development for the treatment of relapsed/refractory multiple myeloma. Phase 1 dose expansion enrollment continues and the Company expects to provide an update on this program later in 2021....P-BCMA-ALLO1, the Company's first allogeneic CAR-T product candidate, is in development for the treatment of relapsed/refractory multiple myeloma. The program is proceeding as planned with an IND filing and initiation of a Phase 1 clinical trial on track for the third quarter of 2021."

Enrollment status • IND • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

[VIRTUAL] P-BCMA-ALLO1 — A Fully Allogeneic Stem Cell Memory T Cell (TSCM) CAR-T Therapy Targeting BCMA for the Treatment of Multiple Myeloma Shows Potent Anti-Tumor Activity (ASGCT 2021) - "Tscm have been correlated with best responses and superior safety in the clinical trial of our P-BCMA-101 autologous product candidate. Notably, anti-tumor efficacy and in vivo CAR-T expansion observed for P-BCMA-ALLO1 was comparable to that of non-gene edited healthy donor CAR-T cell controls.The P-BCMA-ALLO1 product is generated using multiple proprietary components of Poseida’s technology that aim to confer efficacy and persistence, safety and cost effective and consistent manufacturing of our product candidate in the clinic. P-BCMA-ALLO1 could potentially make a significant impact on the treatment of MM."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

Poseida Therapeutics Reports Program Updates and Financial Results for the Fourth Quarter and Full Year 2020 (PRNewswire) - "BCMA Program: (i) P-BCMA-101: Phase 1 dose expansion enrollment continues, with an expected update on this program later in 2021; (ii) P-BCMA-ALLO1: The program is proceeding toward an IND filing, which is expected in the first half 2021; PSMA Program: P-PSMA-101 is a solid tumor autologous CAR-T product candidate being developed to treat patients with metastatic castrate resistant prostate cancer (mCRPC) currently in an ongoing Phase 1 dose escalation trial...The Company intends to provide an additional update on this program later in 2021; MUC1-C Program: P-MUC1C-ALLO1 is proceeding, with an anticipated IND filing and initiation of Phase 1 clinical trial by the end of 2021."

IND • New P1 trial • P1 data • Trial status • Breast Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Multiple Myeloma • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

P-BCMA-101 (IMW-IECT 2021) - No abstract available.

CAR-T Product With Unique Manufacturing Process Appears Safe in the Outpatient Setting (Cancer Therapy Advisor) - P1/2, N=NA; NCT03288493; Sponsor: Poseida Therapeutics, Inc.; "To date, 16 patients have received all study-related treatments in the outpatient setting, said Dr Costello. 'Overall, there appears to be no significant difference in the safety between the 2 manufacturing processes'....'A modified manufacturing process may improve expansion and efficacy, showing how the use of nanoplasmid exemplifies continuous innovation in manufacturing,' said Dr Costello."

Media quote • P1/2 data

Initial Data Suggest P-BCMA-101 CAR-T Cells Safe for R/R MM (Oncology Learning Network) - '"P-BCMA-101 is an autologous CAR-T therapeutic targeting BCMA and comprised of a high percentage of desirable stem cell memory T-cells,' said Caitlin L. Costello, MD...during her presentation at the virtual 2020 ASH Annual Meeting, noting that P-BCMA-101 is designed to increase efficacy while minimizing toxicity."

Media quote