Cosela (trilaciclib)

More recently, the development of short-acting CDK4/6 inhibitors, particularly trilaciclib, has provided the first clinically approved example of pharmacologic myeloprotection in small-cell lung cancer...Cyclotherapy should not be regarded as a failed hypothesis prematurely tested, but as an evolving paradigm requiring refined biological stratification and temporal optimization. Properly implemented, it may redefine cytoprotection and expand the therapeutic latitude of modern oncology.

SCLC therapy has shifted from uniform cytotoxic treatment to a tiered, mechanism-driven algorithm that incorporates PD-L1 blockade, targeted cytotoxics, myeloprotection and refined radiotherapy, raising long-term survival above 20% in selected populations. From a European-practice perspective, current best practice is platinum-etoposide plus a PD-L1 inhibitor for treatment-naïve ES-SCLC, thoracic consolidation radiotherapy in selected responders, lurbinectedin or DLL3-directed clinical trials at relapse, and durvalumab consolidation after chemoradiation in LS-SCLC. Outstanding challenges include a low absolute survival gain from chemo-IO, the absence of validated predictive biomarkers, lineage plasticity, and unequal global access to new agents.

P3, N=120, Recruiting, Pharmacosmos A/S | Not yet recruiting --> Recruiting | Initiation date: Mar 2026 --> Jun 2026

On the basis of 110 ns MD simulations, it was concluded that trilaciclib, tucatinib and olmutinib can be considered candidate inhibitors for HsFN3K inhibition. These drugs are expected to have favourable in-vitro and in-vivo activity inhibiting HsFN3K on the basis of our results. The online version contains supplementary material available at 10.1007/s40203-026-00635-2.

P2, N=49, Recruiting, The First Affiliated Hospital of Xiamen University | Not yet recruiting --> Recruiting | Trial completion date: May 2027 --> Dec 2027 | Initiation date: Jun 2025 --> Dec 2025 | Trial primary completion date: Jun 2026 --> Mar 2027

P2, N=30, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=100, Recruiting, Hebei Medical University Fourth Hospital

P3, N=120, Not yet recruiting, Pharmacosmos A/S

Here, in four randomized clinical trials, we show that the CDK4/6 inhibitor trilaciclib, given in conjunction with a variety of chemotherapeutic regimens and across diverse populations of patients with cancer, mitigates chemotherapy-related expansion of CH clones with mutations in DNA damage response genes, including TP53. This finding was also observed in a syngeneic mouse model of TP53-mutant CH, demonstrating that CDK4/6 inhibition blocks platinum-induced TP53 competitive repopulation through promoting hematopoietic stem and progenitor quiescence and decreasing the stemness advantage of TP53-mutant clones. This represents a proof of concept for a potential pharmacologic strategy to block chemotherapy-induced expansion of preleukemic TP53-mutant clones.

The primary endpoint is overall response. Key secondary endpoints include progression-free survival, duration of response, and overall survival.Clinical trial registration: www.clinicaltrials.gov identifier is NCT06027268.

P=N/A, N=80, Not yet recruiting, Shengjing Hospital of China Medical University; Shengjing Hospital of China Medical University

P2, N=196, Not yet recruiting, Dongguan People's Hospital; Dongguan People's Hospital