P1/2, N=84, Recruiting, Zhejiang ACEA Pharmaceutical Co. Ltd. | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Mar 2025 --> Dec 2026

Based on the results of this systematic review, BCMA-directed therapies such as CAR-T cell therapy and bispecific antibodies demonstrate promising efficacy among patients with anti-CD38 refractory disease. However, additional evidence from randomized clinical trials is necessary to establish best practice guidelines.

P2, N=221, Completed, GlaxoSmithKline | Active, not recruiting --> Completed

The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein)...A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

Vactoserib, a TGF-β 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.

P1, N=31, Completed, TeneoFour Inc. | Recruiting --> Completed | N=80 --> 31 | Trial completion date: Aug 2024 --> Jul 2023 | Trial primary completion date: Jan 2024 --> May 2023

P2, N=221, Active, not recruiting, GlaxoSmithKline | Trial completion date: Aug 2023 --> Jul 2024

CD38 knock-out CAR NK cells also demonstrated significantly higher levels of NK activation markers in co-cultures with both untreated and αCD38-treated MM cell lines. These NAM-cultured NK cells with the combined genetic approach of CD38 knockout and addition of CD38 CAR represent a promising immunotherapeutic tool to target MM.

Finally, we observed proliferation of CD34+CD38- progenitor cells, which might be relevant for lymphocyte proliferation and function, and additionally supporting potential modulating effect. Further analyses are being done to validate these findings.

ISB 1442 has 2 Fab domains binding to distinct CD38 epitopes that do not compete functionally with daratumumab. Treatment with ISB 1442 was well tolerated at the dose levels evaluated. The observed clinical CRS events were moderate and potentially related to macrophage activation following ISB 1442 administration. Updated clinical, biomarker and PK data will be presented for this ongoing study.

SAR442257 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) SAR442257 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.