NCT04594005

CDK4/6 Tumor, Abemaciclib, Paclitaxel

Completed Phase 1, PHASE2 Last updated 18 December 2024

What this trial tests

Phase 1, PHASE2 trial testing abemaciclib+paclitaxel in Tumors in 30 participants. Completed in 10 August 2024.

Timeline

25 February 2021

Primary endpoint
16 July 2024

10 August 2024

Quick facts

Lead sponsor	Yonsei University
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	25 February 2021
Primary completion	16 July 2024
Estimated completion	10 August 2024
Sites	1 location across South Korea

Drugs / interventions tested

• abemaciclib+paclitaxel — full drug profile →

Conditions studied

• Tumors — all drugs for Tumors →

Sponsor

Yonsei University

Who can join

19 and older, any sex, with Tumors. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Cyclin D-dependent kinases (CDKs) are often activated in human cancer owing to various genetic and epigenetic events. This affects regulatory pathways, and it results in uncontrolled proliferation due to loss of checkpoint integrity. Most tumors show increased activity of CDKs, and this permits escape from senescence during the evolution of malignancy.

Among them, cyclin D-CDK4/6-INK4 pathway alterations accelerate G1 progression which provides proliferative and survival advantage to cancer. Therefore, preclinical data demonstrated inhibition of cyclin D-dependent kinase activity have therapeutic benefit. CDK4/6 controls entry into cell cycle progression by regulating Retinoblastoma protein (Rb). The majority of human cancers are known to retain wild-type Rb. In addition, CDK4 amplification and mutations also noted in several tumors. In Rb retained tumors, CDK 4/6 inhibitors reduced Rb phosphorylation and induced G1 arrest. In previous study, CDK4/6 inhibitor showed antitumor activities in Rb-positive breast and colon cancer cell lines. Rapid tumor regression was also noticed in mouse xenograft model. In CDK4 amplified sarcoma cell lines, knockdown of CDK4 inhibited cancer cell proliferation.

Cyclin D1 acts with CDK4 and CDK6 to phosphorylate Rb and promote cell-cycle progression, and CDK4/6 inhibitor might be effective for the patients with CCND1/2/3 amplification/mutation or CDK 4/6 amplification. Therefore, basket trial (NCT03310879) is ongoing for the patients with genomic alterations in CCND1, CDKN2A, or CDK4. Amplification/mutation of CCND1/2/3 and CDK4/6 occurs in approximately 15-30% of various solid tumors; sarcoma, GBM, melanoma, gem cell tumor, and gynecologic tumors Regarding the more potent synergistic effect, paclitaxel demonstrated a rationale for promising combination partner with CDK 4/6 inhibitors. In non-small cell lung cancer cell lines, synergistic anti-tumor activities were reported with paclitaxel combination. Corollary, we planned to conduct the phase Ib/II trial of abemaciclib and paclitaxel combination in CDK4/6 pathway activated tumors as one subgroup of multi-arms in ongoing basket trial.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Programmed cell death in tumor immunity: mechanistic insights and clinical implications.
   Wang M, Yu F, Zhang Y, Li P. · · 2023 · cited 26× · PMID 38283351 · DOI 10.3389/fimmu.2023.1309635
2. Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.
   Sager RA, Backe SJ, Ahanin E, Smith G, et al · · 2022 · cited 26× · PMID 35264774 · DOI 10.1038/s41585-022-00571-8
3. Chemotherapy-Induced Alopecia by Docetaxel: Prevalence, Treatment and Prevention.
   Perez AM, Haberland NI, Miteva M, Wikramanayake TC. · · 2024 · cited 11× · PMID 39330051 · DOI 10.3390/curroncol31090423
4. Recent Developments in Targeting the Cell Cycle in Melanoma.
   Hung C, Nguyen TTT, Poulikakos PI, Polsky D. · · 2025 · cited 4× · PMID 40282469 · DOI 10.3390/cancers17081291
5. Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma.
   Heumann P, Albert A, Gülow K, Tümen D, et al · · 2024 · cited 4× · PMID 38730642 · DOI 10.3390/cancers16091690
6. An open-label, phase IB/II study of abemaciclib with paclitaxel for tumors with CDK4/6 pathway genomic alterations.
   Kim KH, Park C, Beom SH, Kim MH, et al · · 2025 · cited 3× · PMID 39874900 · DOI 10.1016/j.esmoop.2024.104106
7. Sleepyhead, deadly awakening: the dynamics of metastatic organotropism, tumor dormancy and therapeutic implications.
   Sarkar S, P K S. · · 2025 · PMID 41404065 · DOI 10.3389/fonc.2025.1701031