pomalidomide

P3, N=117, Active, not recruiting, European Myeloma Network B.V. | Recruiting --> Active, not recruiting | N=222 --> 117

P=N/A, N=34, Recruiting, Peking University Third Hospital

P2, N=26, Completed, AIDS Malignancy Consortium | Trial completion date: Jan 2026 --> Apr 2025 | Active, not recruiting --> Completed

In the present study, we established a modular synthetic platform to systematically generate a set of PROTAC degrader candidates consisting of the CK1δ-specific inhibitor scaffold, alkyl and PEG linker motifs with various lengths, and Cereblon (CRBN)-engaging pomalidomide and thalidomide derivatives as E3 ligase binders. The most potent PROTAC P1d inhibits the phosphorylation of downstream substrates through CK1δ/ε degradation. We establish the requirement of CUL4ACRBN and the proteasome for the P1d-mediated degradation of CK1δ/ε.

Treatment regimens comprised lenalidomide (n = 36) or thalidomide (n = 15) with daratumumab, and pomalidomide (n = 2) with isatuximab. Most patients (n = 38) received frontline therapy, and all were given thromboprophylaxis according to guidelines, mainly aspirin (73%)...Given the limited number of patients and thrombotic events, and the cytokine data available for only two VTE cases, these associations should be regarded as exploratory and interpreted with caution. Overall, these exploratory findings warrant validation in larger, independent cohorts and may help generate hypotheses on how inflammatory signatures influence thrombotic risk and prophylaxis efficacy in MM patients receiving IMiD/anti-CD38-based regimens.

Mechanistically, TPM3-TRKA degradation by compound 9 was dependent on CRBN-mediated polyubiquitination and proteasomal degradation; accordingly, it was hindered by inhibitors of the proteasome (MG132) or Cullins (MLN4924), by dominant negative Cullin 4A mutant, and by free pomalidomide. Finally, a compound 9 derivative, compound 20, induced in vivo degradation of TMP3-TRKA in KM12 cells mouse xenografts. In conclusion, our study indicated that PROTAC-mediated degradation is an efficient strategy to intercept RET and TRKA oncogenic signaling.

P3, N=614, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.

Given the immune-enhancing effects and excellent safety profile, pomalidomide should be further investigated as an immune-enhancing strategy for an HIV cure.

P3, N=419, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2036 --> Apr 2029

P2, N=200, Not yet recruiting, GlaxoSmithKline

P2, N=208, Active, not recruiting, GlaxoSmithKline | Trial completion date: Feb 2029 --> Mar 2027 | Trial primary completion date: Feb 2029 --> Apr 2025