pomalidomide

P2, N=38, Completed, Mayo Clinic | Active, not recruiting --> Completed

P1/2, N=101, Active, not recruiting, University of Chicago | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=54, Completed, Amgen | Active, not recruiting --> Completed

P1, N=9, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 9

Background: Ciltacabtagene autoleucel (cilta-cel) demonstrated superior progression-free survival (PFS) and overall survival compared to standard of care (SOC; pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone) in patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior lines of therapy (LOTs) in the phase 3 CARTITUDE-4 trial. The increase in the TTNT and sustained benefits in PROs, along with prolonged survival, support cilta-cel as a new SOC treatment for MM patients who are refractory to lenalidomide and have received 1-3 prior LOTs. Importantly, with ~3 years of follow-up, a single infusion of cilta-cel provided patients with a longer delay in worsening of MM related symptoms, functional impacts, and GHS/QoL. The totality of clinical and patient-reported evidence demonstrates the significant benefit of cilta-cel.

Pts were assigned 1:1 to cilta-cel or SoC (pomalidomide, bortezomib, and dexamethasone [PVd]/daratumumab, pomalidomide, and dexamethasone [DPd]). At 33.6-mo median follow-up in CARTITUDE-4, cilta-cel vs SoC significantly increased overall MRD-negativity rates >3-fold in the ITT set, with pts achieving MRD negativity rapidly post cilta-cel. The prognostic value of MRD-negative ≥CR at mo 12 was shown, as median PFS was >3 years in pts with MRD-negative ≥CR at mo 12, regardless of tx. These data further underscore the benefit of cilta-cel, which led to significant >3-fold increases vs SoC in rates of MRD-negative ≥CR at any time and at mo 12, and sustained MRD negativity.

Tal-DP exhibits a deep, long-term impact on efficacy through complementary mechanisms of action and may be especially beneficial in pts with prior BsAb exposure, who typically have unfavorable BL immune profiles. Ongoing analyses of tec-DP from MajesTEC-2 (NCT04722146) will be presented.

P1, N=290, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Sep 2024 --> Aug 2025

P3, N=650, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Oct 2025 --> Feb 2026

P1/2, N=32, Not yet recruiting, University of Aarhus

P3, N=222, Recruiting, Stichting European Myeloma Network | Active, not recruiting --> Recruiting | N=109 --> 222

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=174, Terminated, Amgen | Phase classification: P1/2 --> P1

P1, N=184, Recruiting, Genentech, Inc. | Trial completion date: Jul 2025 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Jan 2026

The original molecular glue degraders (thalidomide, lenalidomide, and pomalidomide) are known to bind to cereblon (CRBN) and alter its surface to induce recruitment, ubiquitination, and degradation of therapeutically valuable neosubstrates (IKZF1, IKZF3, and CK1α). Herein, we describe the medicinal chemistry efforts that resulted in the discovery of SJ3149 as well as other potent and selective CK1α degraders. We report kinetic profiling and parameters of CK1α degradation, ternary complex, antiproliferative effects, in vitro ADME data, and in vivo pharmacokinetic studies with demonstrated oral bioavailability.

P3, N=109, Active, not recruiting, Stichting European Myeloma Network | Recruiting --> Active, not recruiting | N=222 --> 109

P3, N=761, Recruiting, Pfizer | Active, not recruiting --> Recruiting

Using miRNA-21 as a model, we engineered DNA hairpins labeled with JQ-1 and pomalidomide and facilitated the modular assembly of DNA-encoded pre-PROTACs through a hybridization chain reaction. The integration of near-infrared light-mediated photodynamic therapy through an upconversion nanosystem further enhanced the efficacy of the platform with potent in vivo anticancer activity. We anticipate that miRiaTAC represents a significant intersection between dynamic DNA nanotechnology and PROTAC, potentially expanding the versatility of PROTAC toolkit for cancer therapy.

P=N/A, N=586, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | N=1200 --> 586

P1/2, N=258, Recruiting, Sanofi | N=197 --> 258

P2, N=38, Active, not recruiting, Mayo Clinic | Trial completion date: Oct 2025 --> Oct 2024 | Trial primary completion date: Oct 2024 --> Feb 2024

P1, N=61, Completed, Amgen | Phase classification: P1b --> P1

P3, N=440, Not yet recruiting, Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

These observations imply that Pomalidomide treatment influences the T-cell repertoire, particularly in the CD4 + subpopulation during the later stages of treatment, raising speculation about the potential involvement of these lymphocyte expansions in mechanisms related to antitumor immunity.

P4, N=70, Recruiting, Beijing Chaoyang Hospital, Capital Medical University; Beijing Chaoyang Hospital, Capital Medical University

P1/2, N=300, Recruiting, Karyopharm Therapeutics Inc | Active, not recruiting --> Recruiting

P3, N=761, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P1, N=114, Completed, Celgene | Active, not recruiting --> Completed

P1/2, N=30, Active, not recruiting, Joseph Tuscano | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

P1/2, N=316, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Jul 2024

P2, N=120, Active, not recruiting, Zhejiang DTRM Biopharma | Recruiting --> Active, not recruiting

Vactosertib is a safe therapeutic that demonstrates tumor-intrinsic activity and can overcome immunosuppressive challenges within the tumor microenvironment to reinvigorate T-cell fitness. Vactosertib offers promise to improve immunotherapeutic responses in heavily-pretreated MM patients refractory to conventional agents.

Persons with myeloma were randomized to receive an anti-TIGIT (T cell immunoreceptor) or anti-LAG3 (lymphocyte activation gene) antibody followed by combination with pomalidomide and dexamethasone ( NCT04150965 ). Anti-TIGIT responders had higher CD226 expression, natural killer cell activation and lower CD112 expression. These data demonstrate the clinical activity of TIGIT-LAG3 blockade and identify pathway-specific response correlates in myeloma.

P3, N=450, Recruiting, Kite, A Gilead Company | Not yet recruiting --> Recruiting

P2, N=60, Active, not recruiting, Tel-Aviv Sourasky Medical Center | Trial completion date: Oct 2024 --> Sep 2029 | Trial primary completion date: Sep 2024 --> Mar 2026

P1/2, N=43, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P2, N=60, Active, not recruiting, Tel-Aviv Sourasky Medical Center | Recruiting --> Active, not recruiting

P1, N=167, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P2, N=120, Recruiting, Zhejiang DTRM Biopharma | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

P2, N=18, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting

P2, N=78, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P2, N=34, Recruiting, Emory University | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025