pomalidomide

P3, N=795, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jun 2027 --> Apr 2026

P=N/A, N=100, Recruiting, Nanjing University School of Medicine

P1, N=33, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Jun 2022 --> Jun 2025 | Trial primary completion date: Jun 2022 --> Dec 2024

P=N/A, N=27, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting

P2, N=53, Completed, Celgene | Trial primary completion date: Nov 2018 --> Sep 2023

P2, N=67, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Mar 2024 --> Jun 2024 | Trial primary completion date: Mar 2024 --> Jun 2024

P2, N=52, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Jun 2022 --> Jun 2025 | Trial primary completion date: Jun 2022 --> Dec 2024

P2, N=43, Recruiting, Andrew Yee, MD | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2024 --> May 2025

Here, we demonstrated that next-generation immunomodulators called cereblon E3 ligase modulators (CELMoDs), as well as lenalidomide and pomalidomide, expanded Th1-like Vδ2+ γδ T cells from PBMCs in the presence of zoledronic acid (ZA). ZA but not these immunomodulatory drugs upregulated BTN3A1 in monocytes. These results suggest that immunomodulatory drugs and ZA have cooperative roles in expansion of Th1-like Vδ2+ γδ T cells, and provide the important knowledge for clinical application of human Vδ2+ γδ T cells as effector cells.

The most frequently used regimens were Seli-Pomalidomide-dexamethasone(dex) or Seli-Carfilzomib-dex (Seli-Kd) in the del17p group and Seli-Kd in the OHRC and standard-risk groups. Interestingly, our data suggest that Seli is a particularly effective bridging modality for patients preparing for CAR-T cell therapies in our population. Further investigation into this population is warranted, including in earlier lines of therapy, in hopes of seeing a more durable response.

Preclinical studies of mezigdomide have demonstrated its anti-proliferative and apoptotic effects in MM, along with its immune-stimulatory effects and its synergistic activity with other antimyeloma agents, including in lenalidomide-/pomalidomide-resistant MM cell lines and mouse xenograft models. Early-phase clinical trial data indicate notable activity in heavily pretreated patients with RRMM, including those with triple-class-refractory disease, together with a tolerable and manageable safety profile. This review summarizes current preclinical and clinical findings with mezigdomide and its potential future roles in the treatment of MM.

P1, N=289, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2024 --> Aug 2025

P1, N=270, Recruiting, TeneoOne Inc. | Trial completion date: Nov 2028 --> Jul 2031

P1/2, N=300, Active, not recruiting, Karyopharm Therapeutics Inc | Phase classification: P1b/2 --> P1/2 | N=518 --> 300 | Trial completion date: Jan 2025 --> Apr 2027 | Trial primary completion date: Jan 2025 --> Apr 2027

P1/2, N=32, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

Multi-agent regimens incorporating immunomodulatory (IMiD®) agents such as thalidomide, lenalidomide, and pomalidomide have become the preferred standard of care for the treatment of patients with multiple myeloma (MM), resulting in improved survival outcomes. Here, we discuss AEs associated with pomalidomide and present five clinically relevant hypothetical case studies in patients with RRMM to provide scenario-driven guidance regarding treatment selection and AE prevention and management in the clinical setting. Lastly, as new treatment approaches continue to be explored in MM, we also discuss novel cereblon E3 ligase modulator (CELMoD™) agents including iberdomide (CC-220) and mezigdomide (CC-92480).

P1/2, N=61, Recruiting, Omar Nadeem, MD | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

P1, N=242, Completed, Janssen Research & Development, LLC | Active, not recruiting --> Completed

P2, N=29, Active, not recruiting, Emory University | Trial completion date: Aug 2024 --> Mar 2026 | Trial primary completion date: Jul 2024 --> Mar 2025

To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.

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

Based on the cocultures, adding pomalidomide significantly promoted IFN-γ and TNF-α secretion (P < .05). Based on the above clinical and in vitro studies demonstrating the co-administration of pomalidomide with CAR-T cell treatment demonstrated favorable tolerability and therapeutic effectiveness in RRMM or B-cell leukemia/lymphoma.

P2, N=141, Recruiting, Karyopharm Therapeutics Inc | Phase classification: P2b --> P2

P1, N=182, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Dec 2024 --> Jul 2025

P3, N=587, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Oct 2026 --> Dec 2028

P1, N=101, Completed, Pfizer | Active, not recruiting --> Completed

P1/2, N=56, Active, not recruiting, Cristina Gasparetto | Trial completion date: Jan 2023 --> Jan 2025

P2, N=17, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=190 --> 17

P1, N=140, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jun 2024 --> Oct 2024

P3, N=495, Terminated, Oncopeptides AB | Completed --> Terminated; Sponsor assessed all endpoints and collected Overall Survival data for another two years following the primary completion date of 03Feb2021.

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

P2, N=21, Recruiting, Peking University People's Hospital | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Aug 2023 --> Jul 2024

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

P2, N=54, Active, not recruiting, Amgen | Trial completion date: Dec 2025 --> Oct 2024

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

P=N/A, N=50, Not yet recruiting, FengYan Jin

P3, N=466, Not yet recruiting, Celgene

P2, N=43, Recruiting, Shanxi Bethune Hospital

P3, N=492, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P3, N=265, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

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

Cereblon-targeting degraders, including immunomodulatory imide drugs lenalidomide and pomalidomide alongside cereblon E3 ligase modulators like iberdomide and mezigdomide, have demonstrated significant anti-myeloma effects...Despite their evident efficacy, approximately 5% to 10% of MM patients exhibit primary resistance to lenalidomide, and resistance commonly develops over time. Understanding the intricate mechanisms of action and resistance to this drug class becomes imperative for refining and advancing novel therapeutic combinations.