Sarclisa (isatuximab-irfc)

Isatuximab and therapeutics directed against each of the other six new HCL targets are currently in clinical use to treat other disorders. Consequently, leveraging the JunD-RhoH axis has identified a battery of therapies that could be repurposed as new means of treating relapsed or refractory HCL.

P2, N=75, Recruiting, Canadian Myeloma Research Group | Not yet recruiting --> Recruiting

P=N/A, N=50, Recruiting, Pack Health | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Oct 2024 --> Aug 2025

P2, N=40, Recruiting, Goethe University | Not yet recruiting --> Recruiting

Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM)...Prior therapies included: pomalidomide (33%), daratumumab (25%), and isatuximab (4%)...Common grade ≥3 adverse events were neutropenia (33%); infections, any (33%); lung infection (27%); hypophosphatemia (19%); and thrombocytopenia (15%). Elo-PVd is one of the first trials of a quadruplet regimen in relapsed/refractory MM incorporating a monoclonal antibody to show efficacy across diverse prior treatments, including triple class exposed with prior anti-CD38 monoclonal antibody.

The instantaneous change in serum M-protein level was found to be associated with PFS in the final joint model. Using model simulations, we retrospectively supported the Isa 10 mg/kg weekly for 4 weeks, then biweekly (QW/Q2W) dosing regimen of the ICARIA-MM phase III pivotal study, and validated it using the same phase III pivotal study data.

Pts received Isa (10 mg/kg IV) in the Isa-VRd arm and bortezomib (1.3 mg/m2 SC), lenalidomide (25 mg PO), and dexamethasone (20 mg IV/PO) in both arms. More pts had positive-to-negative conversions with Isa-VRd vs VRd, with conversion events increasing over the maintenance period. These data support the benefit of Isa in addition to VRd as initiation therapy, as well as the addition of Isa to Rd during maintenance in transplant-ineligible pts with NDMM.

P2, N=40, Not yet recruiting, Goethe University

P=N/A, N=586, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | N=1200 --> 586

This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes. The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.

P1/2, N=258, Recruiting, Sanofi | N=197 --> 258

She received therapy with rituximab, bortezomib, prednisone, and darbepoetin alfa with partial to no response. After repeated insurance denials for daratumumab, isatuximab was obtained from the manufacturer through their CareASSIST program. Following the completion of 2 cycles of isatuximab (8 doses), significant and sustained red cell recovery was observed.

P1, N=189, Terminated, Pfizer | Active, not recruiting --> Terminated; A business decision was made by Pfizer to terminate the study. Termination was not due to any safety concerns, requests from regulatory authorities, changes to the benefit/risk profile or any new concerns regarding the investigational product.

This systematic review examines the available clinical data on CD34+ cell mobilization, collection, and engraftment in multiple myeloma patients treated with the anti-CD38 monoclonal antibodies daratumumab and isatuximab in clinical trials and in real life...Most studies documented lower circulating CD34+ cells after mobilization compared to controls, leading to higher plerixafor requirements...Overall, anti-CD38 monoclonal antibodies appear to interfere with CD34+ cell mobilization, without consistently leading to significant clinical consequences. Further research is needed to elucidate the underlying mechanisms and define optimal mobilization strategies in this patient population.

P2, N=40, Not yet recruiting, University of Utah

P2; Trial completion date: Sep 2027 --> Jul 2026 | Trial primary completion date: Sep 2026 --> Jun 2026

P1, N=11, Active, not recruiting, Emory University | Trial completion date: Sep 2026 --> Nov 2024 | Trial primary completion date: Sep 2025 --> Nov 2024

P1, N=11, Active, not recruiting, Emory University | Recruiting --> Active, not recruiting | N=25 --> 11

P3, N=534, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | Trial primary completion date: May 2024 --> Nov 2024

P2, N=52, Recruiting, Jacob Laubach, MD | Active, not recruiting --> Recruiting | N=29 --> 52

P1, N=317, Recruiting, Regeneron Pharmaceuticals | Trial completion date: Aug 2032 --> Jan 2033

P1/2, N=197, Recruiting, Sanofi | Trial completion date: Dec 2027 --> Mar 2028 | Trial primary completion date: Dec 2027 --> Jun 2027

Fab' fragments from Obinutuzumab (OBN) and Isatuximab (ISA) were employed in the synthesis of anti-CD20 (Fab'OBN-MORF1) and anti-CD38 (Fab'ISA-MORF1) bispecific engagers...Pretreatment of patient cells with gemcitabine or ricolinostat markedly increased cell surface CD20 and CD38 expression, respectively...Our findings demonstrate DFMT's potential in personalized CLL therapy. Further research is needed to validate these outcomes in a larger number of patient samples and to explore DFMT's applicability to other malignancies.

P=N/A, N=50, Recruiting, Pack Health | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Aug 2023 --> Oct 2024

P1/2, N=424, Active, not recruiting, Celgene | Recruiting --> Active, not recruiting

P2, N=61, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2025 --> Apr 2030

P1, N=56, Completed, Sanofi | Active, not recruiting --> Completed

P3, N=411, Recruiting, University of Heidelberg Medical Center | Not yet recruiting --> Recruiting

P1, N=83, Active, not recruiting, Thomas Martin, MD | Recruiting --> Active, not recruiting

P1, N=15, Terminated, Washington University School of Medicine | Trial completion date: Nov 2028 --> Mar 2024 | Active, not recruiting --> Terminated; Decision made to not move forward with Phase II portion of trial

P3, N=337, Active, not recruiting, Sanofi | Trial primary completion date: Jun 2028 --> Nov 2030

P2, N=46, Recruiting, Intergroupe Francophone du Myelome | Trial completion date: May 2025 --> Mar 2026 | Trial primary completion date: May 2025 --> Mar 2026

In conclusion, [68 Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [68 Ga]Ga-AJ206-PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.

P1, N=6, Not yet recruiting, NYU Langone Health | Trial completion date: Jul 2026 --> Jan 2027 | Initiation date: Jan 2024 --> Jul 2024 | Trial primary completion date: Jul 2025 --> Jan 2026

The escape in the second treatment cycle was prevented by the pretreatment of cells with Ad35K++. Overall, our data demonstrate that Ad35K++ and rILYd4 are efficient co-therapeutics of daratumumab and isatuximab, specifically in multi-cycle treatment regimens, and could be used to improve treatment of multiple myeloma.

P2, N=50, Not yet recruiting, Massachusetts General Hospital | Initiation date: Nov 2023 --> Jun 2024

P2, N=39, Recruiting, Divaya Bhutani | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: May 2024 --> Mar 2025

P1, N=1, Terminated, Washington University School of Medicine | Trial completion date: Mar 2027 --> Jan 2024 | Active, not recruiting --> Terminated; Low accrual

P2, N=53, Recruiting, Medical College of Wisconsin | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025

P1, N=56, Active, not recruiting, Sanofi | Phase classification: P1b --> P1

P1, N=15, Active, not recruiting, Washington University School of Medicine | Phase classification: P1/2 --> P1 | Trial completion date: Dec 2023 --> Nov 2028

P3, N=337, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting