lenalidomide

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

P2, N=37, Recruiting, David Bond, MD | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=150, Completed, Peter MacCallum Cancer Centre, Australia | Unknown status --> Completed

After four cycles of cyclophosphamide, bortezomib, and dexamethasone therapy, he achieved a partial response, followed by complete hematologic response (CR) post eight cycles of lenalidomide, dexamethasone, and bortezomib therapy...Following failure of >4 lines of therapy, he received chimeric antigen receptor T (CAR-T) cell therapy (ciltacabtagene autoleucel) for salvage...This case report highlights MM management complexities in CHIP presence, suggesting potential utility of HSCT and CAR-T cell therapy. Prospective studies are necessary to evaluate the safety and efficacy of these therapies in myeloma patients with concurrent CHIP, aiming to optimize treatment strategies and improve outcomes in this challenging clinical context.

P3, N=660, Completed, Fondazione EMN Italy Onlus | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Jul 2024

P3, N=520, Not yet recruiting, GlaxoSmithKline

Background: Ciltacabtagene autoleucel (cilta-cel) demonstrated superior progression-free survival (PFS) and overall survival compared to standard of care (SOC; pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone) in patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior lines of therapy (LOTs) in the phase 3 CARTITUDE-4 trial. The increase in the TTNT and sustained benefits in PROs, along with prolonged survival, support cilta-cel as a new SOC treatment for MM patients who are refractory to lenalidomide and have received 1-3 prior LOTs. Importantly, with ~3 years of follow-up, a single infusion of cilta-cel provided patients with a longer delay in worsening of MM related symptoms, functional impacts, and GHS/QoL. The totality of clinical and patient-reported evidence demonstrates the significant benefit of cilta-cel.

Background: High dose melphalan and ASCT, followed by lenalidomide (len) maintenance, improves progression-free survival (PFS) in MM but is generally not curative. In newly-diagnosed MM patients with <CR after induction, belamaf every 3 months in conjunction with ASCT and len maintenance appears feasible (at 1.9 mg/kg starting dose), with expected reversible ocular toxicities, and so far has promising rates of sCR, MRD-negativity, and PFS. Accrual and follow-up are ongoing.

MRD testing was performed at 100 days post-autologous stem cell transplant (ASCT) (n=39) and/or after one year of lenalidomide (len) maintenance (n=33)...However, these findings are based on preliminary data from a small cohort, requiring further validation in larger studies. Future research will focus on enhancing sensitivity and validating these findings in a broader patient population.

ViPOR-P is safe without notable additional toxicity, especially neutropenia and neuropathy, compared to ViPOR, and DL3 was identified as the RP2D. Most AEs were hematologic and manageable with G-CSF with rare febrile neutropenia observed. Fixed-duration ViPOR-P x 6C without maintenance resulted in durable CRs, especially in pts with non-GCB DLBCL by IHC and ABC DLBCL by RNA-seq, including refractory and post-CAR-T pts.

This study demonstrates that the ALR regimen has high rates of durable complete and molecular responses, and is feasible as a time-limited initial therapy for patients with both TP53 wild type and mutant MCL. The ALO regimen is feasible with encouraging initial safety and efficacy. MRD and cfDNA analyses provide real-time and non-invasive monitoring of molecular response and mutational evolution, which warrants further evaluation in response-adapted strategy.

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. Isa-VRd followed by Isa-Rd led to greater depth of response of MRD-neg over time, with higher rates of MRD-neg at both the end of initiation and during maintenance compared with the control arm. Results from these analyses continue to demonstrate higher rates of sustMRD-neg over time at 10-5 and 10-6 sensitivity thresholds, and more pts retained MRD-neg status through maintenance phase. More pts had positive-to-negative conversions with Isa-VRd vs VRd, with conversion events increasing over the maintenance period.

Understanding the implication of increasing MRD burden is particularly relevant in patients with NDMM treated with quadruplet therapy (QUAD, consisting of a PI, an IMiD, an anti-CD38 mAb and dexamethasone) and autologous stem cell transplantation (ASCT), since most will reach MRD negativity...Among the 19 patients with MRD-P, 12 (63%) were on observation at time of MRD-P, 2 were receiving single agent lenalidomide, 5 were receiving a QUAD, 17 (89%) had previously obtained MRD negativity at <10-5 including 10 (53%) who had also achieved MRD negativity at 10-6...Outcomes of patients with MRD-P are similar to those of patients with IMWG-defined PD. These findings challenge the paradigm of IMWG-defined PD and paraprotein measurability as minimal parameters for change in therapy and introduction of agents with new mechanisms of action.

Pts were assigned 1:1 to cilta-cel or SoC (pomalidomide, bortezomib, and dexamethasone [PVd]/daratumumab, pomalidomide, and dexamethasone [DPd]). At 33.6-mo median follow-up in CARTITUDE-4, cilta-cel vs SoC significantly increased overall MRD-negativity rates >3-fold in the ITT set, with pts achieving MRD negativity rapidly post cilta-cel. The prognostic value of MRD-negative ≥CR at mo 12 was shown, as median PFS was >3 years in pts with MRD-negative ≥CR at mo 12, regardless of tx. These data further underscore the benefit of cilta-cel, which led to significant >3-fold increases vs SoC in rates of MRD-negative ≥CR at any time and at mo 12, and sustained MRD negativity.

Fixed-duration ViPOR x 6C without maintenance achieved CR in 100% and uMRD in 97% of MCL pts, with ongoing CR in 95% and 73% of TN and R/R pts, respectively, and only 1 R/R pt receiving consolidative allo-HSCT. This includes blastoid, TP53 mutated, and post-BTKi high-risk subsets. ViPOR with a 12d VEN ramp-up on C2 is safe in MCL pts of all ages without significant TLS or febrile neutropenia.

Median prior lines of therapy was 3 (range 2–12), 18 (38%) pts received prior lenalidomide–based therapy, 7 (15%) pts received prior chimeric antigen receptor T-cell therapy (CAR-T), and 4 (9%) received prior CD20 TCE therapy. AZD0486 offers high response rates in pts with R/R FL at target doses ≥2.4 mg. Responses were durable. 2SUD allows safe administration of the target dose up to at least 15 mg.

The presence of both high CTC and HRCA identifies a group of patients with an overall dismal outcome. The addition of daratumumab to VRd induction/consolidation and R maintenance improves outcome in NDMM patients with high-risk disease defined by high CTC, leading to higher rates of deep and sustained MRD-neg and better PFS.

D-VRd resulted in significantly higher rates of overall and sustained MRD negativity at both 10–5 and 10–6 sensitivity thresholds versus VRd at all timepoints in TIE and transplant-deferred patients with NDMM. This deeper response translated into significant improvements in overall PFS in the D-VRd group. Of patients who achieved MRD-negativity (10–5) with D-VRd, >80% were alive and progression-free at 54 months.

For patients (pts) with R/R FL, rituximab + lenalidomide (R2) is an approved and widely accepted regimen based on results from the AUGMENT trial (overall response rate [ORR], 78%; complete response [CR] rate, 34%; estimated 2-y progression-free survival [PFS], 58%). With more than 2 y of follow-up, fixed-duration epcoritamab + R2 continued to show deep and durable responses (CR rate, 87%; estimated 24-mo DOCR, 75%) in pts with R/R FL, irrespective of high-risk features. Considering limitations of cross-trial comparisons, these results (estimated 2-y PFS, 70%) compare favorably with those reported for R2 alone in the AUGMENT trial (estimated 2-y PFS, 58%). The depth of responses was underscored by MRD negativity in 88% of evaluable pts.

In preclinical studies, lenalidomide has been shown to induce cytotoxicity in ABC DLBCL cells by inhibiting NF-κB signaling and a synergistic effect is seen when B-cell receptor signaling is inhibited by the BTK inhibitor ibrutinib. The results of the BGB-3111-110 study demonstrated that the RP2D of zanubrutinib 160 mg twice daily plus lenalidomide 25 mg once daily had a manageable safety profile and promising efficacy in patients with R/R DLBCL. Similar efficacy was observed across DLBCL subtypes; ORR was numerically higher in the ABC subtype. Further molecular analysis is ongoing.

P3, N=389, Completed, Fondazione EMN Italy Onlus | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jul 2024

Accordingly, immunotherapy-induced efficacy could be largely restored in YTHDF2-deficient T cells through combinational use of IKZF1/3 inhibitor lenalidomide in a mouse model. Thus, YTHDF2 coordinates epi-transcriptional and transcriptional networks to potentiate T cell immunity, which could inform therapeutic intervention.

P1, N=13, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=44, Not yet recruiting, Zhejiang Cancer Hospital

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

P2, N=19, Not yet recruiting, Ruijin Hospital

P2, N=26, Active, not recruiting, John Reneau | Trial completion date: Apr 2024 --> May 2025 | Trial primary completion date: Apr 2024 --> May 2025

To compare the safety and efficacy of zanubrutinib plus rituximab and lenalidomide (ZR2) and R-CHOP-like for elderly patients with newly diagnosed DLBCL, we conducted this single-center prospective study. Patients with gastrointestinal DLBCL have to be monitored closely by abdominal enhanced CT every cycle. Overall, ZR2 chemo-free regimen might be more appropriate for elderly DLBCL patients.

P2, N=80, Not yet recruiting, Navy General Hospital, Beijing

P2, N=54, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2024 --> Dec 2024

P2, N=80, Not yet recruiting, Navy General Hospital, Beijing

P3, N=650, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Oct 2025 --> Feb 2026

We showed that inducible ON (iON)-CAR T cells respond to target tumors cells in the presence of venetoclax or the BH3 mimetic navitoclax in a dose-dependent manner, while there is no impact of the drugs on equivalent second generation-CAR T cells. Finally, by fusing a degron sequence to the endodomain of the iON-CAR S-chain we generated an all-in-one ON/OFF-switch CAR, the iONØ-CAR, down-regulated by lenalidomide within 4 to 6 for functionally inactive T cells (no IFNγ production) within 24 h. We propose that our remote-control CAR designs can reduce toxicity in the clinic. Moreover, the periodic rest of iON and iONØ-CAR T cells may alleviate exhaustion and hence augment persistence and long-term tumor control in patients.

L6 exhibited the highest potency against skin cancer A431 cell line, with an IC50 of 0.19 μM compared to 1.8 μM with triapine and showed low toxicity against PNT-2 cells with an SI index of >100 μM. Also, it lowered the ERK1/2 expression, which affected the caspase 3 activity and showed higher binding affinity compared to the FDA-approved drug Lenalidomide in molecular docking studies. Our findings demonstrated the possible future anticancer drug potency of L6 in the skin cancer A431 cells.

P3, N=108, Recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2029 --> Jan 2031

P2, N=130, Recruiting, University of Heidelberg Medical Center | N=70 --> 130 | Trial completion date: Oct 2027 --> Aug 2028 | Trial primary completion date: Oct 2026 --> Feb 2027

P1, N=14, Active, not recruiting, Alliance Foundation Trials, LLC. | Trial primary completion date: Mar 2025 --> Sep 2024

P2, N=53, Recruiting, The First Affiliated Hospital of Xiamen University

P1, N=34, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=360 --> 34 | Trial completion date: Aug 2026 --> Dec 2025 | Trial primary completion date: Aug 2026 --> Feb 2024

Notably, our study identified eight drugs-Bortezomib, Midostaurin, CHIR.99021, JNK.Inhibitor.VIII, Lenalidomide, Sunitinib, GDC0941, and GW.441756-as exhibiting sensitivity toward OS. The outcomes of this investigation present an opportunity to predict the survival outcomes among individuals diagnosed with OS. Furthermore, these findings hold promise for progressing research endeavors focused on prognostic evaluation and therapeutic interventions pertaining to this particular ailment.

P2, N=120, Not yet recruiting, National Cancer Institute (NCI)

Despite application of several new drugs, such as daratumumab, bortezomib/lenalidomide/dexamethasone, in combination with hematopoietic stem cell transplantation, overall prognosis remains poor and the pathological mechanism of MM is still unknown. The present findings suggested that miR-1343-3p may regulate ATG7 and autophagy by directly targeting the 3'UTR of ATG7. To the best of our knowledge, there are no direct data showing the roles of miR-1343-3p in development of MM; however, miR-1343-3p may be considered a potential target for MM treatment.