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.

Tumor progression was suppressed in two patients, in whom clonal expansion of memory- and effector-phenotype CD8+ T cells was observed, along with activation of the IFN-γ signaling pathway. Here, we show that iPSC-iNKT cells are safe and possess therapeutic potential as an immunotherapy for solid tumors.

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.

P1/2, N=130, Recruiting, Kyushu University | N=96 --> 130 | Trial completion date: Jun 2027 --> Mar 2029 | Trial primary completion date: Dec 2026 --> Dec 2028

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

P2, N=30, Recruiting, NKGen Biotech, Inc.

P=N/A, N=46, Recruiting, The First Affiliated Hospital of Zhejiang University School of Medicine; The First Affiliated Hospital of Zhejiang University School of Medicine

P2, N=15, Active, not recruiting, Weill Medical College of Cornell University | Trial completion date: Sep 2027 --> Jan 2028 | Trial primary completion date: Sep 2025 --> Jan 2026

P1/2, N=24, Completed, Dragonfly Therapeutics | Recruiting --> Completed | N=242 --> 24 | Trial completion date: Nov 2027 --> Aug 2025

When compared to a CD3 bispecific with the same c-Met binder, ABBV-303 drove lower levels of inflammatory cytokines at equivalent levels of tumor cell killing and enhanced tolerance of normal cells expressing c-Met, consistent with the natural tendency of NK cells to preferentially react with stressed or cancer cells as compared to normal, healthy tissue. Together, this study showed that ABBV-303 is effective at driving anti-tumor immunity against a wide range of c-Met expressing tumors.

P1, N=27, Terminated, AbbVie | N=192 --> 27 | Trial completion date: Jan 2028 --> Oct 2025 | Recruiting --> Terminated | Trial primary completion date: Jan 2028 --> Oct 2025; Strategic considerations