everolimus

P1, N=40, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business decision and not related to safety concerns

In the present study, we investigated whether combining reduced-dose 177Lu-CD25 Ab radioimmunotherapy (RIT) with molecularly targeted inhibitors of ALK (crizotinib) or mTOR (everolimus) could enhance antitumor efficacy while minimizing systemic toxicity. These findings demonstrate that targeted inhibition of ALK or mTOR synergizes with CD25-directed 177Lu RIT to enhance therapeutic efficacy without increasing toxicity. This combinatorial approach enables radiation-dose reduction while preserving antitumor potency, supporting further preclinical and translational development of 177Lu-CD25-based combination RIT for ALCL and other CD25-expressing malignancies.

P=N/A, N=410, Not yet recruiting, Cook Research Incorporated

P1/2, N=38, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

PRRT combined with everolimus-based immunosuppression has demonstrated controllable safety and preliminary antitumor activity in patients with relapsed NETLM after LT who have been strictly screened, but myelosuppression requires close monitoring and timely symptomatic treatment.

Through an extensive screening process, we identified everolimus and auranofin as inhibitors of PCK1...Interestingly, we also found PCK1 and Cyclin D3 interaction in pancreatic cancer, similar to that in breast cancer, but not in liver cancer. Thus, the results may resolve the puzzle for the role of PCK1 in tumor-promoting or -suppressive role in different cancer types.

P3, N=1069, Active, not recruiting, Eisai Inc. | Trial completion date: Mar 2026 --> Mar 2027

P4, N=80, Not yet recruiting, Dana-Farber Cancer Institute

Long-term exposure to calcineurin inhibitors and mammalian targets of rapamycin inhibitors (mTORis) is thought to support expansion of Breakpoint cluster region-Abelson 1 (BCR::ABL1)-positive hematopoietic clones, but the clinical evidence base is still limited...In view of tacrolimus-related neurotoxicity six months post-transplant, dose reduction was undertaken, and everolimus was introduced...After clinical stabilization, Imatinib 400 mg daily was initiated, alongside pre-emptive reduction of tacrolimus, guided by weekly trough monitoring...Although rare, post-transplant CML warrants high clinical suspicion, routine blood count surveillance, and reflex BCR::ABL1 testing of unexplained leukocytosis. Careful adjustment of immunosuppression allows effective tyrosine kinase inhibitor therapy without compromising graft integrity, but multi-center registries are essential to refine preventative and therapeutic strategies.

This finding suggests that tasquinimod, an S100A9 inhibitor, could be a viable therapeutic option. Furthermore, the interaction between MMP11 and COL16A1 in stroma-rich regions suggests that cancer-associated fibroblasts may contribute to improved outcomes. Our study underscores the critical role of spatial gene expression analysis in elucidating the tumor microenvironment and its impact on prognosis in patients undergoing E+L treatment, thereby opening new avenues for targeted interventions.

P=N/A, N=20, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2028

Patients treated with everolimus had a median PFS of 5 (95% CI: 0.3-10) months, and chemotherapy with streptozocin and 5-fluorouracil resulted in a median PFS of 8 (95% CI: 5-11) months. Re-introduction of PRRT with 2 additional cycles had reduced efficacy compared with the initial treatment. PFS was short in non-somatostatin receptor-based therapies like everolimus and chemotherapy.