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- | SAR442257 / Sanofi
Journal, IO biomarker, Trispecific: A CD38/CD3xCD28 trispecific T-cell engager as a potentially active agent in multiple myeloma patients relapsed and/or refractory to anti-CD38 monoclonal antibodies. (Pubmed Central) - Dec 12, 2024
While complete CD38 loss is not observed upon relapses after treatment with anti-CD38 monoclonal antibodies (mAb), there is downregulation of surface CD38 expression and decreased number and function of NK cells, which renders these patients resistant to retreatment with anti-CD38 mAb. Here, we provide preclinical evidence that RRMM patients previously exposed to anti-CD38 mAb could benefit from T-cell-based immunotherapy that depend less on CD38 antigen density and NK-cell activity, such as the novel CD38/CD3xCD28 trispecific T-cell engager, SAR442257.
- SAR442257 / Sanofi
First-in-Human Phase 1 Study of SAR442257 in Patients with Relapsed/Refractory Multiple Myeloma and Non-Hodgkin Lymphoma (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5617;
P1
Conclusion : This Phase 1 study of SAR'257 showed an anti-tumor response in a small number of pts from the rrMM and rrNHL cohorts. Due to safety concerns, in particular high rates of EBV and CMV reactivation and recurrent episodes of CRS in the higher dose levels, the study was terminated during dose escalation.
- Multiple Myeloma Persister Cells Surviving Bispecific Antibodies and CAR-T Cells Exhibit New CD45+ Expression (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5377;
Conclusion : These data support that (1) CD45 expression increases at the RNA and protein level on MM persisting after TCRT, (2) this is caused by a soluble factor secreted by stimulated T cells, and (3) LAG-3 may be a potential target for post-TCRT MM. The CD45+LAG-3+ phenotype aligns with previous reports of an immunosuppressive response cancer cells may use to provide protection from T cell attack.
- | SAR442257 / Sanofi
Trial completion date: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - Aug 1, 2024
P1, N=47, Active, not recruiting, Sponsor: Sanofi
The CD45+LAG-3+ phenotype aligns with previous reports of an immunosuppressive response cancer cells may use to provide protection from T cell attack. Trial completion date: Aug 2024 --> Mar 2025
- | SAR442257 / Sanofi
Preclinical, Journal, IO biomarker, Trispecific: Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma. (Pubmed Central) - May 24, 2024
inhibitor, was able to mitigate this effect and restore sensitivity to SAR442257 in these experiments. In conclusion, SAR442257 has high potential for enhancing TC cytotoxicity by co-targeting CD38 and CD28 on MM and CD3/CD28 on T cells.
- | SAR442257 / Sanofi
Trial completion date: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - Apr 17, 2024
P1, N=47, Active, not recruiting, Sponsor: Sanofi
In conclusion, SAR442257 has high potential for enhancing TC cytotoxicity by co-targeting CD38 and CD28 on MM and CD3/CD28 on T cells. Trial completion date: Apr 2024 --> Aug 2024
- | SAR442257 / Sanofi, Darzalex (daratumumab) / J&J
Preclinical, Journal, IO biomarker, Trispecific: Ex Vivo Efficacy of SAR442257 anti-CD38 Trispecific T Cell Engager in Multiple Myeloma Relapsed After Daratumumab and BCMA Targeted Therapies. (Pubmed Central) - Feb 29, 2024
My-DST is capable of measuring T cell-dependent killing using the MM patient's own bone-marrow derived T cells. SAR442257 shows promise for MM and may be best suited for patients declared resistant to both CD38 mAbs and BCMA targeted therapy.
- || SAR442257 / Sanofi
Enrollment closed, Trial completion date: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - Feb 23, 2024
P1, N=47, Active, not recruiting, Sponsor: Sanofi
SAR442257 shows promise for MM and may be best suited for patients declared resistant to both CD38 mAbs and BCMA targeted therapy. Recruiting --> Active, not recruiting | Trial completion date: Apr 2026 --> Apr 2024
- SAR442257 / Sanofi
The CD38/CD3xCD28 Trispecific Antibody (SAR442257) Potentially Represents a Novel Therapeutic Strategy for Peripheral T-Cell Lymphomas (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_5823;
SAR 442257 also induced CD25 and CD69 expression on normal T-cells suggesting efficient T-cell activation, (data not shown). Conclusion Altogether, this study shows that 1) most PTCL cells express at least CD28 or CD38, and 2) SAR 442257 can efficiently kill malignant PTCL cells, while ensuring effective T-cell activation; In view of these results, clinical investigation of SAR442257 in PTCL is warranted.
- SAR442257 / Sanofi, Sarclisa (isatuximab-irfc) / Sanofi
A CD38/CD28xCD3 Trispecific T-Cell Engager (TCE) As a Potentially Active Agent for the Treatment of Older Patients with Acute Myeloid Leukemia (AML) (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_5607;
While isatuximab-driven ADCC in AML cell lines and primary samples is dependent on CD38 density in tumor cells, the CD38/CD28xCD3 TCE exerted its anti-tumor efficacy regardless of CD38 density. Thus, AML patients expressing both high and low/heterogenous levels of CD38 could benefit from T cell based immunotherapeutic strategies targeting CD38.
- SAR442257 / Sanofi, Darzalex (daratumumab) / J&J, Sarclisa (isatuximab-irfc) / Sanofi
A CD38/CD28xCD3 Trispecific T-Cell Engager (TCE) As a Potentially Active Agent in Multiple Myeloma Patients Relapsed and/or Refractory (RRMM) to Anti-CD38 Monoclonal Antibodies (mAbs) (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2350;
We observed a reduction in CD38 levels in MMPC and an impaired cytotoxic activity of NK cells in RRMM patients previously exposed to anti-CD38 mAbs. We propose a second targeting of CD38 using T-cell-based immunotherapeutic agents whose efficacy depends less on CD38 antigen density, especially after longer washout periods, as a potential therapeutic strategy in the RRMM setting.
- SAR442257 / Sanofi
Pre-clinical characterization of SAR442257, a CD38xCD28xCD3 trispecific T-cell engager in relapsed/refractory multiple myeloma (In Person) - Sep 10, 2023 - Abstract #IMW2023IMW_540;
We propose a second targeting of CD38 using T-cell-based immunotherapeutic agents whose efficacy depends less on CD38 antigen density, especially after longer washout periods, as a potential therapeutic strategy in the RRMM setting. SAR442257 has increased binding capacity for RRMM due to CD38 and CD28 targets and demonstrated activity on RRMM cells as reasonable alternative for future RRMM therapy approach.
- | SAR442257 / Sanofi
Trial completion date: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - Jul 13, 2023
P1, N=57, Recruiting, Sponsor: Sanofi
SAR442257 has increased binding capacity for RRMM due to CD38 and CD28 targets and demonstrated activity on RRMM cells as reasonable alternative for future RRMM therapy approach. Trial completion date: Jun 2025 --> Apr 2026
- SAR442257 / Sanofi
SAR442257, A CD38/CD28/CD3 TRISPECIFIC ANTIBODY, POTENTIATES CAR T-CELL ACTIVITY AGAINST LARGE B-CELL LYMPHOMA (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_1690;
The CD38/CD28xCD3 trispecific antibody SAR442257 boosted CAR T-cell activity through recognition of CD38 on the tumor, costimulation of CAR T-cells, and induced fratricide of CD38+ T-cells; resulting in superior tumor cell killing. In addition, SAR442257 allowed CD19 CAR T-cells to kill CD19- /CD38+ LBCL cells.
- SAR442257 / Sanofi
SAR442257, a CD38/CD28/CD3 trispecific antibody, potentiates CAR T-cell activity against large B-cell lymphoma () - May 4, 2023 - Abstract #ICML2023ICML_468;
- | SAR442257 / Sanofi
Trial completion date: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - Jul 6, 2022
P1, N=57, Recruiting, Sponsor: Sanofi
In addition, SAR442257 allowed CD19 CAR T-cells to kill CD19- /CD38+ LBCL cells. Trial completion date: Apr 2024 --> Apr 2025
- |||| SAR442257 / Sanofi
CAR T-Cell Therapy: Congratulations Patrick and @GreenLymphoLab @MDAndersonNews @ChrisRFlowersMD Nice write up- Journal Honors Patrick Reville, MD, MPH, As Recipient of the 2022 Young Investigator Award to study Trispecific CD19-directed CAR T cells with SAR442257 https://t.co/kT9GyTUs3q (Twitter) - Jun 22, 2022
- || SAR442257 / Sanofi
After CD28 stimulation was official quasi taboo for years as a result of the TeGenero disaster, more and more companies are now pursuing this approach, e.g. $SNY -> SAR442257 (CD38/CD28XCD3), $XNCR -> B7-H3xCD28, PD-L1xCD28 etc. (Twitter) - Jun 4, 2021
- || SAR442257 / Sanofi
Trial initiation date: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - Dec 27, 2020
P1, N=57, Recruiting, Sponsor: Sanofi
Trial completion date: Apr 2024 --> Apr 2025 Initiation date: Dec 2020 --> Jul 2020
- ||| SAR442257 / Sanofi
Enrollment open: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - Aug 19, 2020
P1, N=57, Recruiting, Sponsor: Sanofi
Initiation date: Dec 2020 --> Jul 2020 Not yet recruiting --> Recruiting
- || SAR442257 / Sanofi
Trial primary completion date: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - Jun 25, 2020
P1, N=57, Not yet recruiting, Sponsor: Sanofi
Not yet recruiting --> Recruiting Trial primary completion date: May 2022 --> Jan 2024
- ||| SAR442257 / Sanofi
New P1 trial: First-in-human Single Agent Study of SAR442257 in RRMM and RR-NHL (clinicaltrials.gov) - May 26, 2020
P1, N=57, Not yet recruiting, Sponsor: Sanofi
- SAR442257 / Sanofi
CD28 expression on multiple myeloma cells enhances the cytotoxic activity of CD38/CD28xCD3 trispecific T cell engager (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_3255;
We further show that when other anti-CD38 antibodies are bound to CD38, binding of SAR442257 to tumor cells and T-cell mediated cytotoxicity are rescued by CD28 as evidenced by loss of binding and cytotoxic activity in CD28KO cells. Overall, these data show that SAR442257 is active on both CD38 high and low MM models and that CD28 expressed on MM tumor cells can be directly targeted by SAR442257, enhancing its cytotoxicity and allowing it to bind MM cells when CD38 is occupied by other anti-CD38 antibodies