pomalidomide

Herein, we report the synthesis of lenalidomide (63% overall yield) and pomalidomide (62% overall yield) using an integrated continuous flow platform with residence times of 42 minutes and 52 minutes, respectively. The products are obtained without the need for column chromatography, and both immunomodulatory imide drugs (IMiDs) can be accessed from a common intermediate through our developed route. Furthermore, we explore the synthesis of CRBN ligand-linkers under continuous flow, affording a series of derivatives with diverse properties in yields exceeding 90%.

P1/2, N=53, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P2, N=67, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

P3, N=228, Recruiting, Qilu Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

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

While ELO alone has shown modest single agent activity, combination with immunomodulatory drugs (IMIDs), such as lenalidomide and pomalidomide (POM), has proven beneficial in treating MM. NK cells exposed to the TCSCTX or CTX+POM from MM cells potentiated NK cell cytotoxicity of MM cells and induced expression of PD-L1 and CD47 on MM cells. Dual targeting of PD-L1 and CD47 using anti-PD-1 and an anti-CD47 antibody significantly enhanced NK cytotoxicity and secretion of anti-tumour effector molecules, TNF-α and granzyme B. These findings support the addition of CTX to ELO-containing MM regimens and provide a rationale for combining POM with immune checkpoint blockade to maximise NK cytotoxicity against MM.

P2/3, N=147, Active, not recruiting, AbbVie Deutschland GmbH & Co. KG | Recruiting --> Active, not recruiting

P2/3, N=322, Active, not recruiting, Celgene Corp. | Recruiting --> Active, not recruiting

P1/2, N=76, Recruiting, AbbVie Deutschland GmbH & Co. KG

P2/3, N=315, Not yet recruiting, Regeneron Pharmaceuticals Inc.

Combining WZ811 with anti-MM agents showed synergism with doxorubicin, dexamethasone, bortezomib, lenalidomide, and pomalidomide, while antagonism was observed with carfilzomib, supporting the clinical assessment of WZ811 in MM.  KEY MESSAGES: WZ811 reduced the viability of myeloma primary cells and cell lines. WZ811 eliminated the MM stem cell-like side population. WZ811 synergized with DOX, DEX, BTZ, LEN, and POM.

P2, N=80, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Feb 2028 | Initiation date: Jan 2026 --> Apr 2026 | Trial primary completion date: Feb 2026 --> Feb 2028