Imbruvica (ibrutinib)

P=N/A, N=55, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Jun 2026 --> Dec 2026

Our findings reveal a reciprocal regulatory relationship between FAK and ROR1, with both proteins enriched in CLL cells that have exited the lymph nodes. Given defactinib's favorable safety profile in solid tumor trials, combining FAK inhibition with BTK inhibitors could enhance therapeutic efficacy by limiting leukemic clone adaptability and addressing resistance and relapse. While anti-ROR1 therapies showed limited efficacy as monotherapy in CLL trials, targeting multiple nodes of this regulatory network may prove more effective.

This premilinary in vitro data suggest a trend toward ibrutinib resistance in Oxphos-type cell lines. More research is warranted both in preclinical models as well as in clinical datasets.

The patient developed persistent severe thrombocytopenia despite multiple lines of therapy, including corticosteroids, intravenous immunoglobulin, rituximab, splenectomy, and thrombopoietin receptor agonists. Subsequent treatments with ibrutinib and a venetoclax-based regimen failed to improve platelet counts and were discontinued due to worsening cytopenia...Refractory thrombocytopenia in CLL should be approached as a manifestation of complex disease biology rather than an isolated complication. This single observation indicates that in TP53 aberrant cases with multi-mechanism thrombocytopenia, disease-directed targeted therapy may contribute significantly to platelet recovery.

The model was further validated by assessing responses to conventional therapies, including ibrutinib and venetoclax. In conclusion, this 3D spheroid model captures key functional aspects of B-T interactions in CLL, maintaining the dynamic interactions between malignant B cells and their autologous immune components, partially reproducing microenvironmental features, and offering a promising platform for preclinical therapeutic evaluation.

P2, N=112, Active, not recruiting, Incyte Corporation | Trial completion date: Sep 2027 --> Nov 2026 | Trial primary completion date: Sep 2027 --> Nov 2026

P2, N=66, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

P1, N=33, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027

The results confirm watch-and-wait as standard of care for early-stage CLL patients, especially in high-risk CLL characterized by del(17p) and/or mutated TP53. EudraCT Number: 2013-003211-22.

Ca2+-flux and cell viability assays using patient-derived BCRs expressed in murine B-cells confirmed reduced ibrutinib efficacy in IGLV3-21R110 cases, especially regarding inhibition of antigen-stimulated signaling. In summary, IGLV3-21R110 is an independent prognostic factor for shorter EFS in early-stage CLL and reduces ibrutinib effectiveness clinically and in vitro.

P1/2, N=87, Active, not recruiting, Kerry Rogers | Trial completion date: Apr 2026 --> Apr 2027

Combination treatment with BTK inhibitor ibrutinib improves anti-tumor efficacy of oHSV in both human GBM12 xenograft and syngeneic murine GSC005 models...Further analysis shows that BTK inhibition, with or without IDO inhibition, promotes the formation of tumor-infiltrating tertiary lymphoid structures (TLS) during intratumoral oHSV treatment, subsequently remodeling T cell, NKT cell, and monocyte-macrophage populations. These results indicate that BTK inhibition exerts multifaceted effects in enhancing the anti-tumor efficacy of oHSV therapy.