- |||||||||| CSF1R Targeting T Cell Engaging Bispecific Antibodies Enable Safe and Efficient Immunotherapies in Acute Myeloid Leukemia (Marriott Grand Ballroom 8-9 (Marriott Marquis San Diego Marina)) - Nov 6, 2024 - Abstract #ASH2024ASH_1636;
While the use of T cell engaging bispecific antibodies (TCE) targeting B cell lineage antigens such as CD19 (Blinatumomab) or CD20 (Epcoritamab, Glofitamab, Mosuenetuzumab) have induced strong and long-lasting response rates in B cell malignancies (Falchi, Vardhana et al...Early clinical trials of CD33-TCE (JNJ-67571244, AMG330) or CD123-TCE (Vibecotamab) have shown modest clinical activity (response rates ranging between 0 to 16,6%) and a high degree of treatment-emergent adverse events (TEAE) (Ravandi, Bashey et al...In summary, we could show the safety and efficacy of CSF1R-TCB in preclinical in vitro and in vivo models and demonstrate the superior safety profile of CSF1R-TCB compared to CD33-TCB in CB-humanized mouse models. In cell line-derived xenograft models of AML, CSF1R-TCB induced anti-leukemia activity, warranting further preclinical and clinical investigations.
- |||||||||| eluvixtamab (AMG 330) / Amgen, Actimmune (interferon gamma-1 b) / Clinigen, Amgen
Sting Activation Improves T-Cell Engaging Immunotherapy of Acute Myeloid Leukemia (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2489;
The beneficial effect of physiological cGAMP in enhancing AMG 330-mediated cytotoxicity was accompanied by the pronounced expression of effector cytokines and an overall cytotoxic T-cell phenotype. We established a key role for interferon gamma in AMG 330-mediated cytotoxicity of AML cells and in rendering AML cells responsive to STING agonism.
- |||||||||| eluvixtamab (AMG 330) / Amgen, Blincyto (blinatumomab) / Astellas, Amgen
Human Plasma Cells Engineered to Produce Bi-Specific T Cell Engagers Show In Vivo Anti-Tumor Efficacy (Board No. 575) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1281;
Finally, immunocompromised mice engrafted with anti-CD19-BiTE secreting plasma cells were resistant to expansion of CD19+ patient derived leukemia, a model that mimics the use of the anti-CD19 BiTE blinatumomab as a bridge to hematopoietic stem cell transplant or potential long-term therapy. These findings support further research into genome engineered human plasma cells for use as a local delivery system of BiTEs for the treatment of leukemias, lymphomas, and possibly other cancers.
- |||||||||| eluvixtamab (AMG 330) / Amgen
STING activation improves T cell engaging immunotherapy of Acute Myeloid Leukemia (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_603;
We hypothesized that combining the CD33 BiTE construct AMG 330 with a cGAS-STING agonist has the potential to reverse immunosuppressive mechanisms and augment anti-leukemic activity...This leads to pronounced expression of effector cytokines and an overall cytotoxic T-cell phenotype, contributing to the beneficial effect of cGAMP in enhancing BiTE construct-mediated lysis. Ethics Approval Peripheral blood or bone marrow samples were collected from healthy donors and patients with acute myeloid leukemia at initial diagnosis, relapse, or complete remission after written informed consent was received in accordance with the Declaration of Helsinki and approval was granted by the Institutional Review Board of the Ludwig-Maximilian-Universität (Munich, Germany, reference number: 216-08).
- |||||||||| eluvixtamab (AMG 330) / Amgen
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Jun 2, 2022
P1, N=96, Terminated,
Ethics Approval Peripheral blood or bone marrow samples were collected from healthy donors and patients with acute myeloid leukemia at initial diagnosis, relapse, or complete remission after written informed consent was received in accordance with the Declaration of Helsinki and approval was granted by the Institutional Review Board of the Ludwig-Maximilian-Universität (Munich, Germany, reference number: 216-08). N=256 --> 96 | Trial completion date: Aug 2023 --> Dec 2021 | Recruiting --> Terminated | Trial primary completion date: Aug 2023 --> Dec 2021; Amgen strategic business decision to cancel following portfolio review, re-prioritization.
- |||||||||| eluvixtamab (AMG 330) / Amgen
Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Feb 25, 2022
P1, N=256, Recruiting,
N=256 --> 96 | Trial completion date: Aug 2023 --> Dec 2021 | Recruiting --> Terminated | Trial primary completion date: Aug 2023 --> Dec 2021; Amgen strategic business decision to cancel following portfolio review, re-prioritization. Trial completion date: Feb 2023 --> Jun 2023 | Trial primary completion date: Feb 2023 --> Jun 2023
- |||||||||| Review, Journal: CD33-Targeted Therapies: Beating the Disease or Beaten to Death? (Pubmed Central) - Dec 16, 2021
Gemtuzumab ozogamicin was the first and only CD33-directed antibody-drug conjugate to be US Food and Drug Administration approved for AML...Promising new strategies include cellular therapy mechanisms and linker molecules. This is an exciting target that requires a considerable amount of precision to yield clinical benefit.
- |||||||||| T Cell Engaging Bispecific Antibodies Produce Durable Response in Mesothelin-Positive Patient-Derived Xenograft Models of Pediatric AML (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2843;
Antibody single-chain variable region (scFv) sequences derived from amatuximab recognizing MSLN and from either blinatumomab or AMG330 targeting CD3 were used to engineer and express two MSLN/CD3-targeting BsAbs: MSLN AMA -CD3 L2K and MSLN AMA -CD3 AMG respectively...Chemotherapy (DA) consisted of 3 doses of 1.5 mg/kg daunorubicin iv and 5 doses of 50 mg/kg cytarabine ip...Conclusion These data validate the efficacy of MSLN-targeting BsAbs in PDX models with endogenous MSLN expression. Because prior MSLN-directed therapies appeared safe in humans, MSLN-targeting BsAbs could be ideal immunotherapies for MSLN-positive pediatric AML patients.
- |||||||||| eluvixtamab (AMG 330) / Amgen
Evolving Exhaustion of T Cells during the Course of the Disease in AML Can be Abrogated By CD33 BiTE® Construct Mediated Cytotoxicity (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2730;
Additionally, T-cell function was assessed after stimulation with 1) CD3/CD28 beads; 2) AMG 330, a CD33/CD3 specific BiTE ® construct, after incubation with OCI-AML3 target cells; or 3) AMG 330 in an autologous ex vivo long-term culture system after incubation with primary AML cells (pAML)...These observations may highlight the significant role of the AML target cells in shaping a T-cell response. To this end, we will further analyze the longitudinal communication between T cells and their corresponding AML blasts.
- |||||||||| eluvixtamab (AMG 330) / Amgen
Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Oct 21, 2021
P1, N=256, Recruiting,
To this end, we will further analyze the longitudinal communication between T cells and their corresponding AML blasts. Trial completion date: Aug 2022 --> Feb 2023 | Trial primary completion date: Aug 2022 --> Feb 2023
- |||||||||| eluvixtamab (AMG 330) / Amgen
Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Jun 3, 2021
P1, N=256, Recruiting,
Trial completion date: Aug 2022 --> Feb 2023 | Trial primary completion date: Aug 2022 --> Feb 2023 Trial completion date: Feb 2025 --> Aug 2022 | Trial primary completion date: May 2023 --> Aug 2022
- |||||||||| eluvixtamab (AMG 330) / Amgen
Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Nov 16, 2020
P1, N=256, Recruiting,
N=20 --> 1 | Trial completion date: Mar 2022 --> Oct 2020 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2022 --> Oct 2020; Amgen Decision Trial completion date: Jun 2024 --> Feb 2025 | Trial primary completion date: Sep 2022 --> May 2023
- |||||||||| eluvixtamab (AMG 330) / Amgen
Enrollment change, Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Jun 29, 2020
P1, N=256, Recruiting,
Not yet recruiting --> Recruiting N=100 --> 256 | Trial completion date: May 2021 --> Jun 2024 | Trial primary completion date: May 2021 --> Sep 2022
- |||||||||| AMG 330 / Amgen, Blincyto (blinatumomab) / Astellas, Amgen, amatuximab (MORAb-009) / Eisai
Mesothelin Targeting Bites for Pediatric AML: In Vivo Efficacy and Specificity (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5655;
1H), suggesting that IgG BiTE was far more efficacious than canonical BiTEs (P<0.01) . Taken together, these data indicate that MSLN-targeting BiTEs could be used as novel immunotherapy for pediatric AML with MSLN expression.
- |||||||||| AMG 330 / Amgen, Blincyto (blinatumomab) / Astellas, Amgen, 4-1BB agonist mAb / Amgen
Impact of p53 Knock-Down on T-Cell Proliferation and T-Cell Mediated Cytotoxicity Against AML Cell Lines Mediated By a CD33 Specific BiTE® Antibody Construct (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_2084;
Proof of concept was shown by Blinatumomab, a CD19xCD3 BiTE® antibody construct, for treatment of r/r B-cell precursor ALL...HD T cells and murine Ba/F3 cells (transduced with CD33 and CD86) were cocultured at an E:T ratio of 1:10 in presence of 5 ng/ml AMG 330 or control BiTE®in the lower compartment...Bulk RNA sequencing of p53 kd AML cell lines compared to p53 wt revealed downregulation of a co-stimulatory ligand 4-1BBL with log2 fold change of - 0.33, -0.30, -0.39 in Molm-13, MV4-11 and OCI-AML3, respectively...We will also characterize primary patient samples for their T-cell-inhibiting capacities, e.g . p53-mutated disease.
- |||||||||| AMG 330 / Amgen
Journal, Myeloid-derived suppressor cells: CD33/CD3-bispecific T-cell engaging (BiTE®) antibody construct targets monocytic AML myeloid-derived suppressor cells. (Pubmed Central) - Oct 28, 2019
This finding was corroborated in experiments showing that adding MDSCs into co-cultures of T- and AML-cells reduced AML-blast killing, while IDO inhibition promotes AMG 330-mediated clearance of AML-blasts. Taken together, our results suggest that AMG 330 may achieve anti-leukemic efficacy not only through T-cell-mediated cytotoxicity against AML-blasts but also against CD33 MDSCs, suggesting that it is worth exploring the predictive role of MDSCs for responsiveness towards an AMG 330-based therapy.
- |||||||||| eluvixtamab (AMG 330) / Amgen
Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Oct 3, 2019
P1, N=70, Recruiting,
Taken together, our results suggest that AMG 330 may achieve anti-leukemic efficacy not only through T-cell-mediated cytotoxicity against AML-blasts but also against CD33 MDSCs, suggesting that it is worth exploring the predictive role of MDSCs for responsiveness towards an AMG 330-based therapy. Trial completion date: Jan 2020 --> Mar 2021 | Trial primary completion date: Jan 2020 --> Mar 2021
- |||||||||| AMG 330 / Amgen
Journal: Bifunctional PD-1 x αCD3 x αCD33 fusion protein reverses adaptive immune escape in acute myeloid leukemia. (Pubmed Central) - Jul 19, 2019
The CD33-targeting bispecific T-cell engager (BiTE) AMG 330 proved to be highly efficient in mediating cytolysis of acute myeloid leukemia (AML) cells in vitro and in mouse models...We conclude that our molecule preferentially targets AML cells, whereas high-affinity blockers, such as clinically approved anti-cancer agents, also address PD-L1 non-AML cells. By combining the high efficacy of T-cell engagers with immune checkpoint blockade in a single molecule, we expect to minimize irAEs associated with the systemic application of immune checkpoint inhibitors and suggest high therapeutic potential, particularly for patients with relapsed/ refractory AML.
- |||||||||| eluvixtamab (AMG 330) / Amgen
Enrollment change, Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Dec 20, 2018
P1, N=70, Recruiting,
By combining the high efficacy of T-cell engagers with immune checkpoint blockade in a single molecule, we expect to minimize irAEs associated with the systemic application of immune checkpoint inhibitors and suggest high therapeutic potential, particularly for patients with relapsed/ refractory AML. N=50 --> 70 | Trial completion date: May 2020 --> Jan 2020 | Trial primary completion date: May 2020 --> Jan 2020
- |||||||||| eluvixtamab (AMG 330) / Amgen
Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Oct 29, 2018
P1, N=50, Recruiting,
N=50 --> 70 | Trial completion date: May 2020 --> Jan 2020 | Trial primary completion date: May 2020 --> Jan 2020 Trial completion date: Jun 2019 --> May 2020 | Trial primary completion date: Jun 2019 --> May 2020
- |||||||||| eluvixtamab (AMG 330) / Amgen
Trial completion date, Trial primary completion date: A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies (clinicaltrials.gov) - Jun 20, 2018
P1, N=50, Recruiting,
Trial completion date: Jun 2019 --> May 2020 | Trial primary completion date: Jun 2019 --> May 2020 Trial completion date: Jun 2018 --> Jun 2019 | Trial primary completion date: Jun 2018 --> Jun 2019
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