lenalidomide

P1, N=30, Recruiting, Oncotherapeutics | Not yet recruiting --> Recruiting | Initiation date: Jan 2024 --> Dec 2022

Our data suggest that reduced CSN5 expression leads to abnormalities in the ubiquitination cycle of CRL4A, resulting in the inhibition of LEN-mediated degradation of IKZF1 and IKZF3. These findings delineate an additional mechanism of LEN resistance in MM cells and may contribute to the development of alternative therapeutic strategies to overcome LEN resistance.

P2, N=76, Active, not recruiting, Seoul National University Hospital | Recruiting --> Active, not recruiting

P1/2, N=17, Active, not recruiting, Hackensack Meridian Health | Trial completion date: Nov 2024 --> Sep 2025 | Trial primary completion date: Nov 2024 --> Sep 2025

P1/2, N=237, Recruiting, Hoffmann-La Roche | Trial completion date: Nov 2027 --> Oct 2030 | Trial primary completion date: Nov 2025 --> Oct 2028

P1/2, N=60, Recruiting, Enterome | Trial completion date: Sep 2029 --> May 2032 | Trial primary completion date: Jun 2025 --> May 2026

The complete response rate was 25.0% and 42.9% in the lenalidomide 15- and 20-mg cohorts, respectively. Due to acceptable toxicity and preliminary efficacy, the lenalidomide 20-mg dose was selected for further investigation.

Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.

P2, N=61, Active, not recruiting, Omar Nadeem, MD | Recruiting --> Active, not recruiting | Trial completion date: Mar 2029 --> Dec 2030 | Trial primary completion date: Mar 2026 --> Dec 2026

P1/2, N=543, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting

P1, N=25, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

In summary, we report the involvement of ADAR1-regulated dsRNA-sensing in modulating lenalidomide sensitivity in MM. These findings highlight a novel RNA-related mechanism underlying lenalidomide resistance and underscore the potential of targeting ADAR1 as a novel therapeutic strategy.

P2, N=34, Not yet recruiting, Northwestern University

P3, N=128, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Dec 2027 --> Aug 2027

Lenalidomide, a derivative of thalidomide, is a type of immunomodulatory drug (IMiD) that has been standard therapy for multiple myeloma (MM) and other hematologic malignancies for almost two decades. In addition, treatment with IMiDs is also associated with an increased risk for myelodysplastic neoplasms (MDS), squamous cell carcinoma of the skin, and, less frequently, acute lymphoblastic leukemia (ALL). We present a case of an elderly male with MM and multiple subsequent skin cancers, who presented with pancytopenia and was diagnosed with B-lymphoblastic leukemia (B-ALL) after 10 years of maintenance lenalidomide therapy.

In the current ADVANCE study (NCT04268498), patients are randomly assigned to receive 8 cycles of carfilzomib-lenalidomide-dexamethasone with or without daratumumab (i.e. Dara-KRd versus KRd). High-dose melphalan (HDM) followed by autologous stem cell transplant (ASCT) is only offered to patients who remain MRD positive after 8 cycles with all patients transitioning to maintenance lenalidomide...Using MRD testing after completed combination therapy, patients will only be offered HDM-ASCT if they remain MRD-positive after 8 cycles; otherwise, they collected stem cells will be stored (delayed transplant) and transition to maintenance therapy. The aim of this translational effort is to define the underlying biology of sustained MRD negativity in NDMM patients.

Background and Significance : Lenalidomide (LEN) maintenance after autologous stem cell transplant (ASCT) therapy extends disease control in multiple myeloma (McCarthy PL, et al...EHA 2024 abstr 958).The IBEX trial, described herein, is a Phase II trial designed to evaluate the combination of IBER and subcutaneous DARA (IBER+DARA(SC)) as maintenance therapy in myeloma pts who remain MRD(+) following ASCT.Study Design and Methods : The primary objective is to assess the efficacy of post-ASCT IBER+DARA(SC) maintenance as reflected by capacity to induce MRD(-) responses using the commercially available ClonoSEQ assay with a 10-5 sensitivity...Subcutaneous DARA is weekly for cycles 1-2, every other week for cycles 3-6, then monthly thereafter, following the DARA schedule currently being used in the S1803 trial. Patients will be treated for up to 2 years on this study (26 cycles of therapy).This study is registered with ClinicalTrials.gov : ID NCT06107738

P2, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2027

P3, N=436, Active, not recruiting, Assistance Publique - Hôpitaux de Paris | Trial primary completion date: Jul 2024 --> Jul 2026

P3, N=395, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jan 2027 --> Jan 2026

P2, N=21, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P3, N=500, Recruiting, Genmab | Trial completion date: Jun 2030 --> Oct 2030 | Trial primary completion date: Nov 2029 --> Oct 2030

P2, N=25, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Nov 2024 | Trial primary completion date: Jun 2025 --> Nov 2024

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.

P3, N=1080, Recruiting, Genmab | Trial completion date: May 2037 --> Nov 2037 | Trial primary completion date: May 2037 --> Nov 2037

P2, N=622, Recruiting, Genmab | Trial completion date: Nov 2032 --> Jun 2031 | Trial primary completion date: Nov 2032 --> Jun 2031

P3, N=247, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

These interactions are crucial for the observed inhibitory activity. Molecular dynamics simulation revealed the binding event of the most active compound with class I histone deacetylase and the stability of the complex in a biological environment.

P1, N=18, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2026 --> Feb 2025 | Trial primary completion date: Oct 2026 --> Feb 2025

P1/2, N=68, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Sep 2024 --> Dec 2024

P2, N=20, Recruiting, University of Alabama at Birmingham | Trial primary completion date: Jan 2025 --> Jan 2026

P2, N=35, Active, not recruiting, Weill Medical College of Cornell University | Trial primary completion date: Sep 2024 --> Feb 2025

The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma. Blocking MHC-I or depleting T cells alleviates the defective erythropoiesis of PRCA, suggesting that the interaction between erythroid cells with elevated MHC-I and T cells in the bone marrow might contribute to PRCA. Taken together, our study implicates a mechanism underlying lenalidomide-induced PRCA in treating cancer patients.

P1/2, N=142, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Sep 2024 --> Mar 2025

Teclistamab (Tec), a bispecific antibody (BsAb) targeting BCMA, shows promise in refractory MM and, when combined with daratumumab (Tec-Dara), may help eliminate residual disease...Prior therapy exclusions apply, except for limited doses of dexamethasone, bortezomib, cyclophosphamide, lenalidomide, or daratumumab...The study seeks to determine if AHCT can be deferred in patients achieving MRD negativity after Dara-VRd without compromising the chance of reaching and sustaining MRD negativity, and whether post-AHCT Tec-Dara can enhance sustained MRD negativity rates compared to post-AHCT Dara-R in MRD-positive patients. The study is currently open for enrollment at multiple sites in the US.

P=N/A, N=15, Recruiting, Bristol-Myers Squibb

P=N/A, N=100, Recruiting, Peking University People's Hospital

P1/2, N=53, Recruiting, Beijing Mabworks Biotech Co., Ltd. | Phase classification: P1b/2 --> P1/2 | Trial primary completion date: May 2024 --> Jan 2024

P3, N=168, Recruiting, Beijing Mabworks Biotech Co., Ltd. | Trial primary completion date: Mar 2024 --> Mar 2025

P2, N=54, Completed, Amgen | Active, not recruiting --> Completed

P2, N=44, Recruiting, Zhejiang Cancer Hospital | Not yet recruiting --> Recruiting

P1, N=18, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=40 --> 18