P2, N=210, Recruiting, Shaperon | Not yet recruiting --> Recruiting

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

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

P2/3, N=230, Recruiting, MediciNova | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2/3, N=230, Recruiting, MediciNova | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=50, Active, not recruiting, MediciNova | Phase classification: P1b/2a --> P1/2

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=56, Not yet recruiting, Hospices Civils de Lyon

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

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.

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

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

P2, N=43, Recruiting, Shanxi Bethune Hospital

P2, N=120, Not yet recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group

Collectively, our results show the successful IL-10 encapsulation, slow release to prolong its biological half-life and reduce inflammatory cytokines IL-6 and TNF production in vitro and in mice. Our results serve as proof of concept to further explore the therapeutic prospective of encapsulated IL-10 for biomedical applications, including inflammatory diseases.

P1, N=56, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=99 --> 56

In orthotopic and lung metastatic breast cancer models, FTF-BL-CP produced notable therapeutic benefits of retarding tumor growth, extending survivals, and inhibiting lung metastasis. Therefore, this ECM-trapping strategy provides an encouraging possibility of prolonging tumor retention to potentiate the antitumor immunity for anticancer immunotherapy.

P2, N=190, Recruiting, Mayo Clinic | Trial primary completion date: Mar 2024 --> Nov 2024

P2, N=120, Recruiting, VA Office of Research and Development | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

P1, N=67, Recruiting, Exeliom Biosciences

P2, N=26, Active, not recruiting, AIDS Malignancy Consortium | Recruiting --> Active, not recruiting

Thalidomide and its analogs are molecular glues (MGs) that lead to targeted ubiquitination and degradation of key cancer proteins via the cereblon (CRBN) E3 ligase...In this platform, automated, high throughput, and nano scale synthesis of hundreds of pomalidomide-based MGs was combined with rapid phenotypic screening, enabling an unprecedented fast identification of potent CRBN-acting MGs...This revealed E14 as a potent MG degrader targeting IKZF1/3, GSPT1 and 2 with profound effects on a panel of cancer cells. In a more generalized view, integration of automated, nanoscale synthesis with phenotypic assays has the potential to accelerate MGs discovery.

While cereblon-modulating agents, such as pomalidomide and lenalidomide, have been found to improve the immune profile, the efficacy of their impact in combination with other treatments is yet unknown. The prognostic significance for the number of immune markers is only seen in the PVd arm and none of these immune markers exhibit prognostic values in the Vd arm. This study demonstrates the importance of the immunomodulatory effects and the therapeutic benefit of adding pomalidomide to Vd treatment.

Pomalidomide, a widely used E3 ligase recruiter in PROTACs, can independently degrade other proteins, including zinc-finger (ZF) proteins, with vital roles in health and disease...Modifications of appropriate size on the C5 position reduced off-target ZF degradation, which we validated through target engagement and proteomics studies. By applying these design principles, we developed anaplastic lymphoma kinase oncoprotein-targeting PROTACs with enhanced potency and minimal off-target degradation.

P2/3, N=230, Recruiting, MediciNova | Phase classification: P2b --> P2/3

P=N/A, N=150, Active, not recruiting, Celgene | Recruiting --> Active, not recruiting

P=N/A, N=600, Recruiting, Celgene | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

CD3 expression was a good predictor for tumor progression for five months in recurrent GBM patients treated with MN-166 and TMZ. T cell infiltration within GBM tumors has been an active area of research with the success of immune checkpoint blockade (ICB) therapies in other cancers. Moreover, MN-166 has been shown to impact immune suppressive myeloid cells, which are linked to the immune suppressive tumor microenvironment and a resistance mechanism to ICB.

Here, we develop several PROTAC molecules by covalently linking the antibiotic trimethoprim (TMP) to pomalidomide, a ligand for the E3 ligase, Cereblon...Finally, we show multiplexed regulation with another known degron-PROTAC pair, as well as reversible protein regulation in a rodent model of metastatic cancer, demonstrating the formidable strength of this system. Altogether, TMP PROTACs are a robust approach for selective and reversible degradation of eDHFR-tagged proteins in vitro and in vivo.

P2, N=145, Completed, The Cleveland Clinic | Active, not recruiting --> Completed

P2, N=45, Terminated, Oncotherapeutics | Unknown status --> Terminated; Lack of enrollment

A good example is the use of immunomodulatory drugs (IMiDs, lenalidomide [LEN] & pomalidomide [POM]) for the treatment of multiple myeloma (MM) which are now standard-of-care, but their use is frequently complicated by neutropenia because of neutrophil maturation impairment. We present a multiomic atlas of normal myelopoiesis which we believe will provide an important resource for the study or normal and perturbed neutrophil development. We use this platform to study IMiD-induced neutropenia and identify two aberrant cellular progenitor populations (aberrant myeloid precursors & erythroid progenitors) with distinct molecular properties as the likely cause of myelosuppression.

We included all pts with ≥2 paired bone marrow samples before and after an IMiD-based treatment (lenalidomide [LEN], thalidomide [T], pomalidomide [POM]) (baseline and relapse samples) and analyzed the patterns of molecular lesions of 42 CRBNPGs (based on Sievers et al. Notably, new/enriched mutations in other genes, beyond CRBNPGs, with known roles as MM drivers cannot be excluded as alternative explanations for these relapses. Additional and more complex, genomic or non-genomic, mechanisms may account for relapse from IMiD-based regimens.

The incubation of erythrocytes from symptomatic DBA patients with antioxidant N-acetylcysteine in vitro led to normalization of ROS levels in erythrocytes. Similarly, the treatment of Rpl5- and Rps19-haploinsufficienct MEL cells with a pro-inflammatory cytokine inhibitor pomalidomide, resulted in the amelioration of oxidative DNA damage (assessed by the presence of 8-oxoguanine, 8-oxoG) and reduction of p53 activation...The potential link between oxidative damage, inflammatory cytokines, and cancer risk in DBA also deserves further research. Grant support: The Ministry of Education, Youth and Sports of the Czech Republic (8F20005), European Union - Next Generation EU, Program EXCELES (LX22NPO5102); Internal grant of Palacky University (IGA_LF_2023_002).

Our results confirm the efficacy of the long-term oral pomalidomide administration (4 mg/day) after BCMA CAR T-cell infusion in patients with R/R MM. Notably, this combination regieme reduced the recurrence rate and prolonged progression-free survival for R/R MM patients, providing a promising option for treating R/R MM. In addition, oral administration of pomalidomide did not significantly prolong the persistence of BCMA CAR T-cells in vivo.

P1, N=9, Completed, Nanexa AB | Initiation date: May 2023 --> Nov 2022

P2, N=75, Completed, Xalud Therapeutics, Inc. | Active, not recruiting --> Completed

P1, N=9, Completed, Nanexa AB | Recruiting --> Completed | Initiation date: Nov 2022 --> May 2023 | Trial primary completion date: Jun 2023 --> Sep 2023

P2; Trial primary completion date: Aug 2023 --> Jul 2024