Sarclisa (isatuximab-irfc)

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

P2, N=16, Active, not recruiting, Intergroupe francophone du myelome | Recruiting --> Active, not recruiting

P1, N=90, Completed, Sanofi | Active, not recruiting --> Completed

P2, N=49, Recruiting, UNC Lineberger Comprehensive Cancer Center | Not yet recruiting --> Recruiting

P2, N=39, Not yet recruiting, Oncotherapeutics | Initiation date: Dec 2023 --> Mar 2024

P3, N=411, Not yet recruiting, University of Heidelberg Medical Center

P1, N=30, Recruiting, Elvira Umyarova | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, Elvira Umyarova

P1/2, N=424, Recruiting, Celgene | Trial completion date: Jul 2026 --> Nov 2026 | Trial primary completion date: Nov 2023 --> Nov 2026

P2, N=29, Active, not recruiting, Jacob Laubach, MD | Recruiting --> Active, not recruiting | N=43 --> 29 | Trial completion date: Mar 2024 --> Jan 2029 | Trial primary completion date: Dec 2023 --> Sep 2025

P2, N=198, Recruiting, Arbeitsgemeinschaft medikamentoese Tumortherapie

Although the SLAMF7-targeting antibody elotuzumab has no single- agent activity, there is clinical synergy between elotuzumab and immunomodulatory drugs in patients with relapsed/refractory disease. Daratumumab and isatuximab are CD38-targeting antibodies which have single-agent activity and a favorable safety profile, which make these agents an attractive component of combination regimens...All therapeutic antibodies may interfere with assessment of complete response. Next-generation Fc-engineered monoclonal antibodies are in development with the potential to further improve the outcome of patients with MM.

P1, N=177, Active, not recruiting, Pfizer | Phase classification: P1a/1b --> P1 | Trial completion date: Mar 2025 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024

P2, N=50, Active, not recruiting, EMN Research Italy | Trial primary completion date: Mar 2025 --> Nov 2023

P2, N=5, Active, not recruiting, OHSU Knight Cancer Institute | Recruiting --> Active, not recruiting | N=44 --> 5

P1/2, N=197, Recruiting, Sanofi | N=123 --> 197 | Trial completion date: Nov 2028 --> Dec 2027 | Trial primary completion date: Nov 2028 --> Dec 2027

P3, N=791, Active, not recruiting, Intergroupe Francophone du Myelome | Recruiting --> Active, not recruiting

P1, N=317, Recruiting, Regeneron Pharmaceuticals | Phase classification: P1b --> P1

Qualitative interviews among individuals with RRMM provided insight into the challenges but also hope associated with chronic management of their condition. Treatment with isatuximab regimens was perceived as logistically manageable with few side effects. Though some individuals felt their long-term experience with MM made the coaching less impactful, coaching was generally perceived as a positive experience, with many individuals self-reporting benefits related to health behaviors and outcomes.

Background: Continuous lenalidomide in combination with dexamethasone (Rd), with bortezomib and dexamethasone (VRd) or, more recently, with daratumumab and dexamethasone (DRd) is the standard first-line (1L) therapy for transplant-ineligible multiple myeloma (MM) patients (pts)...Selinexor is a first-in-class, oral, XPO1 inhibitor indicated for use in combination with bortezomib and dexamethasone (SVd) in adults with relapsed and refractory (RR) MM who have received at least one prior line...Anti-CD38-based regimens approved in 2L+ RR MM, ie, daratumumab + Vd (DVd), daratumumab + carfilzomib + dexamethasone (DKd), and isatuximab + Kd (IKd) report the lowest PFS HRs vs Vd for LEN-refractory pts... This is the first two-step approach NMA linking the disconnected networks of treatments available for LEN-refractory pts using efficacy results for this subgroup from their respective RCTs. Excluding anti-CD38-based regimens, which are unlikely to be used in a 2L+ setting with DRd increasingly prescribed in 1L, SVd is the most efficacious treatment option for LEN-refractory pts among commonly used combinations such as PVd, Kd, and pomalidomide-based regimens, with a reduction of 48% in the risk of progression vs Vd. Moreover, among the regimens included in the OS network, SVd had the largest OS improvement vs Vd.

Patients (aged ≥18 years) with a confirmed MM diagnosis receiving all ixazomib-based regimen as 2nd-line and above therapy (RR-MM), or as a 1st-line therapy (ND-MM) will form group one and TCR-MM patients' refractory to at least one IMiD (lenalidomide, pomalidomide or thalidomide), one PI (bortezomib, ixazomib, or carfilzomib) and one anti-CD-38 monoclonal antibody (daratumumab and isatuximab) will form group two. Descriptive statistics will be used for the analyses. Our findings will also help clinicians in making strategic decision about more apt positioning of ixazomib in the treatment algorithm of MM.

This MAIC analysis demonstrated a significant benefit in PFS and a positive trend in the improvement of OS with IsaKd compared with that with DRd. These findings with a longer follow-up were consistent with the previous analyses conducted with a follow-up of 2 years. These data highlight the therapeutic potential of IsaKd, a lenalidomide-free regimen, in RRMM patients receiving one to three prior LoT compared with a lenalidomide-based regimen.

Treatment regimens in the RWD sources included various combinations of PIs (carfilzomib- and bortezomib-based regimens were each used by 43% and 15% of patients, respectively), IMiDs (lenalidomide- and pomalidomide-based regimens were used by 9% and 41% of patients, respectively), and mAbs (daratumumab- and isatuximab-based regimens were used by 32% and 1% of patients, respectively), among other agents (eg, selinexor-based regimens were used by 5% of patients). 66, respectively). CONCLUSIONSAmong BCMA-naïve patients who resemble those enrolled in the MM-3 trial, those treated with ELRA exhibit significantly longer PFS and OS compared with real-world treatments.

Introduction: Findings from a previously conducted matching-adjusted indirect comparison (MAIC) between isatuximab plus pomalidomide and dexamethasone (IsaPd) and daratumumab plus pomalidomide and dexamethasone (DaraPd) among relapsed and/or refractory multiple myeloma (RRMM) patients receiving at least two prior lines of therapy (LoT) including lenalidomide and a proteasome inhibitor (PI) demonstrated a significantly better overall survival (OS) and a positive trend for progression-free survival (PFS), overall response rate (ORR), and very good partial response or better (≥VGPR) rates with IsaPd than that with DaraPd, with a similar safety profile for both treatments [Leleu X et al, Value in Health 2022; 25(1): S39]. This MAIC analysis demonstrated a significant benefit in OS and a positive trend in the improvement of PFS, ORR, and ≥VGPR in favor of IsaPd compared with DaraPd. These findings were consistent with the previous MAIC with a longer follow-up data (present analysis used a maximum follow-up of 4. 5 years of OS data from both trials, whereas the previous analysis used a follow-up of 3 years from ICARIA and unknown from APOLLO), which highlights the therapeutic potential of IsaPd in RRMM, particularly for patients who become refractory to lenalidomide and a PI.

We review common toxicities associated with agents approved for RRMM in the past 5 years, including the anti-CD38 monoclonal antibody isatuximab, the antibody-drug conjugate belantamab mafodotin, the bispecific antibody teclistamab, the chimeric antigen receptor (CAR) T cell products idecabtagene vicleucel and ciltacabtagene autoleucel, the selective inhibitor of nuclear export compound selinexor, and the drug-peptide conjugate melflufen, as well as toxicities associated with emerging agents for RRMM including additional bispecific antibodies, the BCL-2 inhibitor venetoclax, and the cereblon E3 ligase modulators iberdomide and mezigdomide. We searched the published literature using PubMed, plus congress abstracts, for the above list of drug names or classes and 'myeloma.' Optimal management of toxicities associated with these recently approved and emerging therapies will be critical in maximizing clinical benefit and aiding widespread adoption in routine clinical practice. We summarize current recommendations and guidelines and provide expert insights into supportive care requirements.

This study demonstrates that stem cell collection is feasible after prolonged induction with isatuximab-RVd without collection failures and might be further explored as induction therapy.

P3, N=307, Completed, Sanofi | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Nov 2023