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DRUG:

rimiducid (AP1903)

i
Other names: AP1903
Associations
Company:
Bellicum
Drug class:
Apoptosis stimulant
Associations
2ms
Enrollment change • CAR T-Cell Therapy • Metastases
|
P-MUC1C-ALLO1 • rimiducid (AP1903)
4ms
Trial primary completion date • Combination therapy • Minimal residual disease
|
Erbitux (cetuximab) • cyclophosphamide • fludarabine IV • TROP2-CAR-NK • rimiducid (AP1903)
5ms
T-Cell Therapy for Advanced Breast Cancer (clinicaltrials.gov)
P1, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSLN (Mesothelin)
|
cyclophosphamide • rimiducid (AP1903)
7ms
P-PSMA-101 CAR-T Cells in the Treatment of Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Advanced Salivary Gland Cancers (SGC) (clinicaltrials.gov)
P1, N=60, Active, not recruiting, Poseida Therapeutics, Inc. | Trial primary completion date: Sep 2023 --> Oct 2024
Trial primary completion date • CAR T-Cell Therapy • Metastases
|
rimiducid (AP1903)
8ms
New P1 trial • Combination therapy • Minimal residual disease
|
Erbitux (cetuximab) • cyclophosphamide • fludarabine IV • TROP2-CAR-NK • rimiducid (AP1903)
8ms
P-CD19CD20-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With B Cell Malignancies (clinicaltrials.gov)
P1, N=100, Recruiting, Poseida Therapeutics, Inc. | Initiation date: Jan 2024 --> Apr 2024
Trial initiation date • CAR T-Cell Therapy
|
CD20 (Membrane Spanning 4-Domains A1) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
CD20 positive
|
RG6540 • rimiducid (AP1903)
8ms
Safety Study of Gene Modified Donor T Cell Infusion After Stem Cell Transplant for Non-Malignant Diseases (clinicaltrials.gov)
P1, N=1, Terminated, Bellicum Pharmaceuticals | Active, not recruiting --> Terminated; due to lack of enrollment and changes to the sponsor development portfolio
Trial termination
|
CD34 (CD34 molecule) • HLA-B (Major Histocompatibility Complex, Class I, B)
|
CaspaCIDe DLI (rimiducid activated rivogenlecleucel) • rimiducid (AP1903)
9ms
P-BCMA-ALLO1-001: P-BCMA-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Multiple Myeloma (clinicaltrials.gov)
P1, N=231, Recruiting, Poseida Therapeutics, Inc. | N=135 --> 231 | Trial completion date: Mar 2040 --> Dec 2039 | Trial primary completion date: Jun 2025 --> Dec 2027
Enrollment change • Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
RG6538 • rimiducid (AP1903)
10ms
P-CD19CD20-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With B Cell Malignancies (clinicaltrials.gov)
P1, N=100, Recruiting, Poseida Therapeutics, Inc. | Not yet recruiting --> Recruiting | N=70 --> 100
Enrollment open • Enrollment change • CAR T-Cell Therapy
|
CD20 (Membrane Spanning 4-Domains A1) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
CD20 positive
|
RG6540 • rimiducid (AP1903)
12ms
Trial primary completion date • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
|
PD-L1 expression • BRAF V600E • HR positive • HER-2 negative • BRAF V600 • TROP2 expression
|
cyclophosphamide • fludarabine IV • TROP2-CAR-NK • rimiducid (AP1903)
1year
Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells in Patients With Advanced Solid Tumors (TROPIKANA) (clinicaltrials.gov)
P1, N=54, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Oct 2023
Enrollment open • Trial initiation date • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
|
PD-L1 expression • BRAF V600E • HR positive • HER-2 negative • BRAF V600 • TROP2 expression
|
cyclophosphamide • fludarabine IV • TROP2-CAR-NK • rimiducid (AP1903)
1year
Safety & Activity of Controllable PRAME-TCR Therapy in Previously Treated AML/MDS or Metastatic Uveal Melanoma (clinicaltrials.gov)
P1/2, N=4, Terminated, Bellicum Pharmaceuticals | N=28 --> 4 | Unknown status --> Terminated; company decision
Enrollment change • Trial termination • Metastases
|
PRAME (Preferentially Expressed Antigen In Melanoma)
|
PRAME expression
|
BPX-701 • rimiducid (AP1903)
1year
New P1 trial • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
|
PD-L1 expression • BRAF V600E • HR positive • HER-2 negative • BRAF V600 • TROP2 expression
|
cyclophosphamide • fludarabine IV • TROP2-CAR-NK • rimiducid (AP1903)
1year
Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant (clinicaltrials.gov)
P1/2, N=187, Terminated, Bellicum Pharmaceuticals | Active, not recruiting --> Terminated; Sponsor decision
Trial termination
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B)
|
CaspaCIDe DLI (rimiducid activated rivogenlecleucel) • rimiducid (AP1903)
1year
New P1 trial • CAR T-Cell Therapy
|
CD20 (Membrane Spanning 4-Domains A1) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
CD20 positive
|
RG6540 • rimiducid (AP1903)
over1year
T-Cell Therapy for Advanced Breast Cancer (clinicaltrials.gov)
P1, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSLN (Mesothelin)
|
HER-2 negative • MSLN expression
|
cyclophosphamide • rimiducid (AP1903)
over1year
GPC3-CAR T Cells Co-Expressing IL15 Mediate Potent Antitumor Activity in Liver Cancer Patients Associated with Toxicity That Can Be Mitigated Using iC9 Safety Switch (ASGCT 2023)
Expansion of 15.CAR T cells could be rapidly controlled using rimiducid, the inducible caspase 9 (iC9) safety switch alleviating side effects in all three patients that required its use (Figure 1C,D).15.CAR T cells had higher peak expansion than CAR T cells in the peripheral blood (6.77 x 107 vs 3.71 x 103 copy number/mcg DNA; p=0.016), and both groups demonstrated similar levels of tumor trafficking based on transgene qPCR from tumor biopsies (Figure 2A) which was likely due to the early use of iC9 in the 15.CAR group to alleviate AEs resulting lower number of 15.CAR T cells captured post-iC9 use...These results correspond to response rates of 0% for CAR T versus 50% for 15.CAR T treated patients (Figure 2C-E). Based on results from these phase I studies, co-expression of IL15 leads to increased but manageable toxicity with use of the iC9 safety switch, superior expansion of GPC3-CAR T cells resulting in more potent antitumor activity.
Clinical • CAR T-Cell Therapy
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AFP (Alpha-fetoprotein) • IL15 (Interleukin 15)
|
rimiducid (AP1903)
over1year
Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies (clinicaltrials.gov)
P1/2, N=44, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Mar 2023 | Trial primary completion date: Jun 2023 --> Mar 2023
Trial completion • Trial completion date • Trial primary completion date
|
IL15 (Interleukin 15)
|
cyclophosphamide • fludarabine IV • mesna • CaspaCIDe DLI (rimiducid activated rivogenlecleucel) • rimiducid (AP1903)
over1year
Anti-CD19 CAR-T Cells With Inducible Caspase 9 Safety Switch for B-cell Lymphoma (clinicaltrials.gov)
P1, N=30, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Oct 2038 --> Mar 2043 | Trial primary completion date: Oct 2023 --> Mar 2027
Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
ALK positive • BCL6 rearrangement • BCL2 rearrangement
|
cyclophosphamide • fludarabine IV • rimiducid (AP1903)
over1year
Caspase-9-mediated cleavage of vimentin attenuates the aggressiveness of leukemic NB4 cells. (PubMed, Mol Cell Biochem)
Considering the favorable effect of this strategy in keeping down the malignant features of the leukemic cells, the effect of the iC9/AP1903 system in combination with all-trans-retinoic acid (ATRA) treatment was evaluated. The obtained data prove that iC9/AP1903 significantly makes the leukemic cells more sensitive to ATRA.
Journal
|
VIM (Vimentin) • CASP9 (Caspase 9) • MMP9 (Matrix metallopeptidase 9)
|
VIM expression
|
rimiducid (AP1903)
almost2years
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)
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.
Clinical • P1 data • CAR T-Cell Therapy • IO biomarker • Metastases
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IFNG (Interferon, gamma) • CCL4 (Chemokine (C-C motif) ligand 4) • CSF2 (Colony stimulating factor 2) • IL18 (Interleukin 18) • IL6R (Interleukin 6 receptor) • CD40 (CD40 Molecule) • CX3CL1 (C-X3-C Motif Chemokine Ligand 1) • IL1R1 (Interleukin 1 receptor, type I) • PSCA (Prostate Stem Cell Antigen 2)
|
BPX-601 • rimiducid (AP1903)
almost2years
Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant (clinicaltrials.gov)
P1/2, N=187, Active, not recruiting, Bellicum Pharmaceuticals | Phase classification: P2 --> P1/2
Phase classification
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B)
|
CaspaCIDe DLI (rimiducid activated rivogenlecleucel) • rimiducid (AP1903)
2years
Abrogation of Immune Effector Cell Neurotoxicity Syndrome (ICANS) By Rimiducid (RIM) in Patients Treated with CD19-Specific Chimeric Antigen Receptor Modified T-Cells (CAR-T) Engineered with an Inducible Caspase 9 (iC9 CAR.19)—Clinical and Pharmacodynamic Correlates (ASH 2022)
While early use of corticosteroids (CS) and tocilizumab have improved the management of cytokine release syndrome (CRS), CS are the mainstay of ICANS management...Subjects underwent lymphodepletion with fludarabine and cyclophosphamide followed by infusion of iC9 CAR.19 cells at one of two dose levels (DL1: 5 x 105 CAR-T cells/kg; DL2: 1 x 106 CAR-T cells/kg)... RIM administration to patients with ICANS is associated with abrupt reduction of circulating iC9 CAR.19 cells and ICANS grade. Despite detection of CAR-T cells at 3 weeks post infusion and the observance of remissions after treatment with RIM, further investigation of the effects of RIM on iC9 CAR.19 persistence and antileukemic activity is warranted. Lower, potentially less ablative doses of RIM are being explored.
Clinical • PK/PD data
|
CD19 (CD19 Molecule) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • NGFR (Nerve Growth Factor Receptor)
|
cyclophosphamide • fludarabine IV • Actemra IV (tocilizumab) • rimiducid (AP1903)
2years
Clinical • CAR T-Cell Therapy • IO biomarker
|
AFP (Alpha-fetoprotein) • IL15 (Interleukin 15)
|
GPC3 expression
|
rimiducid (AP1903)
2years
INTERLEUKIN-15 CO-EXPRESSION INDUCES ROBUST IN VIVO EXPANSION AND ANTITUMOR EFFECT OF GLYPICAN-3-SPECIFIC CAR T CELLS IN A PATIENT WITH LIVER CANCER (ILCA 2022)
Patients receive lymphodepletion on Days -4, -3 and -2 with cyclophosphamide and fludarabine followed by T cell infusion on four dose levels (DL1: 3 x 107, 1 x 108, 3 x 108, 1 x 109/m2 CAR+ cells)...This rapid CAR T cell expansion was associated with grade 4 cytokine release syndrome which was not controlled by IL6, IL1 or Tumor necrosis factor-alpha inhibition, but was rapidly relieved by a reduced dose (0.04 mg/kg) of rimiducid, activator of iC9... GPC3-CAR T cells are safe and well tolerated. Results from patient 1 on the AGAR study suggest that co-expression of IL15 with GPC3-CAR in T cells can induce robust expansion and antitumor activity of transduced effectors and that associated toxicities can be mitigated with partial iC9 activation selectively removing the IL15 co-expressing T cell subset.
Preclinical • CAR T-Cell Therapy • IO biomarker
|
IL6 (Interleukin 6) • AFP (Alpha-fetoprotein) • GPC3 (Glypican 3) • IL15 (Interleukin 15)
|
GPC3 expression
|
cyclophosphamide • fludarabine IV • rimiducid (AP1903)
over2years
Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies (clinicaltrials.gov)
P1/2, N=36, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2022 --> Jun 2024 | Trial primary completion date: Jun 2022 --> Jun 2023
Trial completion date • Trial primary completion date
|
CD19 (CD19 Molecule) • IL15 (Interleukin 15)
|
cyclophosphamide • fludarabine IV • mesna • CaspaCIDe DLI (rimiducid activated rivogenlecleucel) • rimiducid (AP1903)
over2years
P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM) (clinicaltrials.gov)
P1/2, N=105, Terminated, 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.
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • CAR T-Cell Therapy
|
IL6 (Interleukin 6)
|
P-BCMA-101 • rimiducid (AP1903)
over2years
Interleukin-15 Co-Expression Induces Robust in vivo Expansion and Antitumor Effect of Glypican-3-Specific CAR T Cells in a Patient with Liver Cancer (ASGCT 2022)
Patients receive lymphodepletion on Days -4, -3 and -2 with cyclophosphamide and fludarabine followed by T cell infusion on four dose levels (DL1: 3 x 107, 1 x 108, 3 x 108, 1 x 109/m2 CAR+ cells)...This rapid CAR T cell expansion was associated with grade 4 cytokine release syndrome which was not controlled by IL6, IL1 or Tumor necrosis factor-alpha inhibition, but was rapidly relieved by a reduced dose (0.04 mg/kg) of rimiducid, activator of iC9... GPC3-CAR T cells are safe and well tolerated. Results from patient 1 on the AGAR study suggest that co-expression of IL15 with GPC3-CAR in T cells can induce robust expansion and antitumor activity of transduced effectors and that associated toxicities can be mitigated with partial iC9 activation selectively removing the IL15 co-expressing T cell subset.
Preclinical • CAR T-Cell Therapy • IO biomarker
|
IL6 (Interleukin 6) • AFP (Alpha-fetoprotein) • GPC3 (Glypican 3) • IL15 (Interleukin 15)
|
GPC3 expression
|
cyclophosphamide • fludarabine IV • rimiducid (AP1903)
over2years
T-Cell Therapy for Advanced Breast Cancer (clinicaltrials.gov)
P1, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSLN (Mesothelin)
|
HER-2 negative • MSLN expression
|
cyclophosphamide • rimiducid (AP1903)
almost3years
Administration of Autologous CAR-T CD19 Antigen With Inducible Safety Switch in Patients With Relapsed/Refractory ALL (clinicaltrials.gov)
P1/2, N=54, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Oct 2036 --> Apr 2041 | Trial primary completion date: Nov 2021 --> Apr 2026
Clinical • Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
CD19 (CD19 Molecule)
|
CD19 positive • CD19 expression
|
cyclophosphamide • fludarabine IV • iC9-CAR19 cells • rimiducid (AP1903)
almost3years
Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies (clinicaltrials.gov)
P1/2, N=36, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
Enrollment closed
|
CD19 (CD19 Molecule)
|
cyclophosphamide • fludarabine IV • mesna • rimiducid (AP1903)
almost3years
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, Poseida Therapeutics, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jun 2022 --> Mar 2024 | Trial primary completion date: Dec 2021 --> Mar 2024
Clinical • Enrollment closed • Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
IL6 (Interleukin 6)
|
P-BCMA-101 • rimiducid (AP1903)
3years
Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies. (PubMed, Front Immunol)
The results obtained in the animal model corroborate in vitro data, since iC9.CAR.CD19 tumor cells were controlled in vivo by the activation of the suicide gene through administration of AP1903. Altogether, our data indicate that the inclusion of the iC9 suicide gene may result in a safe CAR-T cell product, even when manufacturing starts from biological materials characterized by heavy leukemia blast contamination.
Clinical • Journal
|
CD19 (CD19 Molecule)
|
rimiducid (AP1903)
3years
[VIRTUAL] EXPLORING A SAFETY SWITCH IN NKG2D AND BCMA CAR NK-92MI IMMUNOTHERAPY (IMW 2021)
In order to obtain a safe allogeneic immunotherapy, CAR NK-92MI cells expressing a suicide gene therapy have been generated (99.9% purity) being susceptible to death (near 99% death) upon induction with Rimiducid (AP1903)... CAR NK-92MI effectors expressing single and dual CARs have been generated and they all show higher in vitro antitumor efficacy against different MM targets compared to parental NK-92MI cells. In vivo experiments show the inefficacy of irradiated CAR NK-92MI cells as therapeutic strategy in our MM model, leading to the necessity of a combination with a safety switch to ensure an effective and safe off-the-shelf NK immunotherapy for MM treatment.
Clinical • IO biomarker
|
CD19 (CD19 Molecule) • CASP9 (Caspase 9) • NKG2D (killer cell lectin like receptor K1)
|
rimiducid (AP1903)
over3years
T-Cell Therapy for Advanced Breast Cancer (clinicaltrials.gov)
P1, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=36 --> 186
Clinical • Enrollment closed • Enrollment change
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSLN (Mesothelin)
|
HER-2 negative • MSLN expression
|
cyclophosphamide intravenous • rimiducid (AP1903)
over3years
T-Cell Therapy for Advanced Breast Cancer (clinicaltrials.gov)
P1, N=36, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jun 2022
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSLN (Mesothelin)
|
HER-2 negative • MSLN expression
|
cyclophosphamide intravenous • rimiducid (AP1903)
over3years
[VIRTUAL] EXPLORING A SAFE AND EFFECTIVE 'OFF-THE-SHELF' CELL-BASED IMMUNOTHERAPY FOR THE TREATMENT OF MULTIPLE MYELOMA USING NON-IRRADIATED CAR NK-92MI CELLS (EHA 2021)
To settle these drawbacks, CAR NK-92 MI cells expressing suicide gene therapy have been generated (99.8% purity, Figure 1C) and it has been demonstrated that cells can be rapidly eliminated in vitro upon induction with Rimiducid (AP1903)...The co-expression of both CARs results in cytotoxic coverage against different MM targets. In vivo, these data show the futility of irradiation as an NK-92 CAR treatment strategy in our MM model and the further need of combinations with iCasp9 safety switch to ensure the safety and efficacy of the therapy.
IO biomarker
|
CD19 (CD19 Molecule) • NKG2D (killer cell lectin like receptor K1)
|
rimiducid (AP1903)
almost4years
Overcoming target epitope masking resistance that can occur on low-antigen-expresser AML blasts after IL-1RAP chimeric antigen receptor T cell therapy using the inducible caspase 9 suicide gene safety switch. (PubMed, Cancer Gene Ther)
We confirmed that the expression of IL-1RAP CAR by an IL-1RAP+ leukemic cell, by decreasing the membrane availability of the targeted antigen, can induce resistance while a high epitope density maintains sensitivity to CAR T cells. Moreover, the presence of the iCASP9/Rimiducid suicide system safety switch makes this immunotherapy approach safe for application in a future phase 1 clinical trial.
Clinical • Journal • CAR T-Cell Therapy • IO biomarker
|
CD19 (CD19 Molecule) • CASP9 (Caspase 9)
|
CD19 expression
|
rimiducid (AP1903)
4years
Safety Study of Gene Modified Donor T-cells Following TCR Alpha Beta Depleted Stem Cell Transplant (clinicaltrials.gov)
P2, N=193, Active, not recruiting, Bellicum Pharmaceuticals | Trial completion date: Dec 2021 --> Feb 2033
Clinical • Trial completion date
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD4 (CD4 Molecule)
|
CaspaCIDe DLI (rimiducid activated rivogenlecleucel) • rimiducid (AP1903)
4years
[VIRTUAL] Phase I Study of Adoptive Immunotherapy with HA-1-Specific CD8+ and CD4+ Memory T Cells for Children and Adults with Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Trial in Progress (ASH 2020)
We developed a transgene with 4 components: 1) a high-affinity T-cell receptor (TCR) specific for the hematopoietic-restricted minor H antigen, HA-1 that is presented on HLA-A*02:01; 2) a CD8 co-receptor to enhance function of the class I-restricted TCR in CD4+ T cells so they promote cytotoxic CD8+ T cell function and survival; 3) an inducible caspase-9 safety switch, which can be triggered by the drug rimiducid in case of in vivo toxicity; and 4) a CD34-CD20 epitope to facilitate selection of the engineered product during manufacturing and track HA-1 TCR T cells in the recipient...Fludarabine lymphodepletion will be used in most subjects, followed by a single T-cell infusion, with an option for a subsequent infusion(s) if the subject demonstrates an initial response without severe toxicity...The ongoing phase I trial is actively recruiting patients. Development of T-cell immunotherapy targeting other minor H antigen/HLA combinations is also underway to increase the broad applicability of minor H antigen-targeted T-cell immunotherapy.
Clinical • P1 data • IO biomarker
|
CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • CD34 (CD34 molecule) • CASP9 (Caspase 9)
|
fludarabine IV • rimiducid (AP1903)
4years
[VIRTUAL] Preclinical Development of Inducible MyD88/CD40 (iMC)-Enhanced Chimeric Antigen Receptor Natural Killer (GoCAR-NK) Cells to Target BCMA+ Tumors (ASH 2020)
Activated NK cells were transduced with retrovirus encoding an optimized iMC and IL-15-expressing BCMA CAR construct (iMC-BCMA.z-IL15) where iMC signaling could be activated by exposure to rimiducid (Rim), a small molecule dimerizing ligand...iMC/IL-15-enhanced BCMA GoCAR-NK cells proliferation was associated with improved control of tumor outgrowth in mice challenged with BCMA+ myeloma cells. Summary: These results indicate that the synergistic activity of iMC signaling combined with transgenic IL-15 production can enhance BCMA-specific CAR-NK cytotoxicity, cytokine production, long-term proliferation and persistence and may improve overall anti-tumor efficacy of a potential OTS cell therapy for the treatment of myeloma.
Preclinical
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • NCAM1 (Neural cell adhesion molecule 1) • CSF2 (Colony stimulating factor 2) • CD40 (CD40 Molecule) • GLI2 (GLI Family Zinc Finger 2) • IL21 (Interleukin 21)
|
rimiducid (AP1903)
4years
[VIRTUAL] Safety and Antitumor Effects of CD19-Specific Autologous Chimeric Antigen Receptor-Modified T (CAR-T) Cells Expressing the Inducible Caspase 9 Safety Switch (iC9-CAR19 T Cells) in Adult Acute Lymphoblastic Leukemia (ALL) (ASH 2020)
Though most patients with CRS or ICANS experience toxicities that can be managed with supportive care including corticosteroids and tocilizumab, 46% experience grade 3-4 CRS and 13% experience grade 3 ICANS (Maude SL et al N Engl J Med 2018; 37:439)...Subjects underwent lymphodepletion with fludarabine and cyclophosphamide and CAR-T cells were subsequently infused at one of two dose levels (DL1: 5 x 105 CAR-T cells/kg; DL2: 1 x 106 CAR-T cells/kg)...The recommended phase 2 cell dose, 1 x 106 transduced cells/kg is being tested in an expansion cohort. A dose finding study to determine the effects of rimiducid on CRS/ICANS grade, CAR-T cell persistence and cytokine levels is being conducted among expansion cohort patients who experience CRS/ICANS not responding to standard supportive care.
Clinical
|
CD19 (CD19 Molecule) • CASP9 (Caspase 9)
|
fludarabine IV • Actemra IV (tocilizumab) • cyclophosphamide intravenous • rimiducid (AP1903)