Zykadia (ceritinib)

P2, N=216, Completed, Melanoma Institute Australia | Trial completion date: Dec 2025 --> Mar 2026

P1/2, N=1000, Recruiting, Oslo University Hospital HF | N=6000 --> 1000

In vivo, ceritinib suppresses tumor growth, while GLUT1 knockdown reduces its efficacy and ferroptotic response. These findings reveal a novel mechanism whereby ceritinib induces ferroptosis via GLUT1 downregulation and AMPK-dependent ferritinophagy, supporting its potential repurposing for breast cancer therapy.

Specifically, we utilized a human naïve phage display library to identify humanized monoclonal antibodies with high affinities for PD-L1, followed by constructing the single-chain variable fragments (scFvs) and chemically conjugating to ceritinib-loaded biomimetic exosomes (Cer-BEs) that were prepared via two different methods of ultrasonic extrusion and freeze-thaw...Compared to freeze-thaw, ultrasonic extrusion yielded PD-L1@Cer-BEs with smaller particle sizes, higher homogeneity, superior encapsulation efficiency and stability, enhanced anti-tumor effectiveness in vitro and vivo, indicating ultrasonic extrusion is more suitable for constructing PD-L1@Cer-BEs with desirable physicochemical properties and bioactivity. These findings not only prove the novelty and effectiveness of PD-L1@Cer-BEs targeting PDAC but also underscore the critical role of BE preparation in determining the efficacy of antibody-drug conjugate (ADC)-like targeted BEs.

Alectinib demonstrated a clear survival advantage over crizotinib, consistent with trial findings. Lorlatinib showed potential benefit over alectinib, though limited by sample size and wide confidence intervals. This study provides the largest claims-based analysis of 1 L ALK TKIs and may help guide differentiation among agents with equivalent guideline placement.

P1, N=21, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Apr 2026 --> Mar 2027

P3, N=603, Completed, Institut National de la Santé Et de la Recherche Médicale, France | Active, not recruiting --> Completed

Although FDA (Food and Drug Administration) approved inhibitors such as crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib have improved clinical outcomes, their efficacy is often challenged by resistance mechanisms, including secondary kinase domain mutations and activation of bypass pathways. Binding free energies and per-residue contributions were computed using MMGBSA. Boltz-2 machine learning platform to predict KD values and the top three hits were validated using PCA and free energy landscape.

P2, N=10, Terminated, National Cancer Institute (NCI) | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated; Inadequate accrual rate

In this phase IV open-label study, patients with ALK-positive metastatic NSCLC that progressed on first-line alectinib or ceritinib received lorlatinib 100 mg once daily. Lorlatinib continued to show clinically meaningful benefit in patients with previously treated ALK-positive metastatic NSCLC. clinicaltrials.gov identifier is NCT04362072.

Concurrent targeting of PI3K and IR/IGF-1R signaling effectively overcomes adaptive resistance in PIK3CA-mutant NSCLC, supporting the rationale for further clinical evaluation of this combined therapeutic strategy.

We report a 19-year-old male with ALK-rearranged, radioiodine-refractory PDTC who started systemic therapy with ceritinib, achieving a complete metabolic response. Treatment with the third-generation ALK inhibitor led to a deep and durable complete metabolic response, sustained for more than four years, including persistence of remission after treatment discontinuation, with minimal toxicity. This case highlights the potential role of sequential ALK inhibition to overcome acquired resistance in ALK-rearranged TC and underscores the importance of comprehensive molecular profiling to guide personalized treatment strategies in rare aggressive thyroid cancers.