Abstract 3787
Background
XZP-3287 is a novel selective inhibitor of cyclin-dependent kinases 4/6 (CDK 4/6). Preclinical data suggested a comparable antitumor activity with Palbociclib and Abemaciclib, and a more favourable safety profile of mild myelosupression. A continuous dosing schedule (28days/cycle) is adopted in this first-in-human study to achieve sustained target inhibition.
Methods
The study is designed as an accelerated titration followed by a standard 3 + 3 dose escalation. Eligible patients are those with locally advanced or metastatic solid tumours, and who have progressed despite of refractory to standard therapy or no standard-of-care therapy is available.
Results
16 subjects were enrolled in this study by April 1, 2019. The DLT evaluation in 320mg QD dose group was completed. No DLT or drug related serious adverse event (SAE) was observed from 20mg QD to 320mg QD dose groups. The drug related adverse events (AE) were mainly CTCAE grade 1 and 2, and reversible. Drug-related AEs (≥10%) were diarrhea (31.3%), leucopenia (31.3%), blood creatinine increased (25%), anemia (18.8%), neutropenia (18.8%), vomiting (18.8%), ALT increased (12.5%), thrombocytopenia (12.5%), blood alkaline phosphatase increased (12.5%) and hyperuricaemia (12.5%). Myelosuppression was observed from 160mg QD level. A negative correlation was showed between the AUC/Cmax of steady state and the maximum percentage decrease from baseline of neutrophil/platelet counts (r=-0.57 to-0.48), which was consistent with pharmacological effects of CDK4/6 inhibition. Furthermore, clinical activity was observed at low and not yet optimal dose levels. Among 7 efficacy evaluable subjects, 3 achieved SD , and 4 experienced PD. 1 SD patient in 240mg QD dose group had sustained SD for over 8 months and the target lesions was reduced by 23.7% from baseline which previously treated by chemotherapy, The latest data (Apr.30.) showed that, all the 3 patients in 320mg QD dose group achieved SD (2 patients exhibited tumor shrinkage by 10.9% and 8.3% respectively). These data will be update at annual meeting.
Conclusions
This study demonstrated that single-agent XZP-3287 was well tolerated and showed the CDK4/6 inhibition activity in human.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Xuanzhu Biopharmaceutical Ltd.
Funding
Xuanzhu Biopharmaceutical Ltd.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4732 - Progesterone Receptor Isoform Ratio Dictates Antiprogestins/Progestins Effects on Metastatic Breast Cancer Models
Presenter: Maria Abascal
Session: Poster Display session 2
Resources:
Abstract
5737 - PAM50 and CGH-array genomic characterization of HER2-Equivocal Breast Cancers defined by the 2018 ASCO/CAP recommendations.
Presenter: Carine Ngo
Session: Poster Display session 2
Resources:
Abstract
1096 - OncotypeDX® predictive nomogram for recurrence score output: a machine learning system based on quantitative immunochemistry analysis - ADAPTED01
Presenter: Fabio Marazzi
Session: Poster Display session 2
Resources:
Abstract
5426 - Geriatric parameters predict both disease-related and patient-reported outcomes in older patients with breast cancer
Presenter: Willeke van der Plas-Krijgsman
Session: Poster Display session 2
Resources:
Abstract
5865 - Patients with a 21-gene assay in South East London differ from the TAILORx trial population
Presenter: Charalampos Gousis
Session: Poster Display session 2
Resources:
Abstract
1312 - Predictive tools in adjuvant breast cancer – what is the standard of evidence supporting their utility? A literature review examining validation of Adjuvant!, Cancermath and NHS Predict
Presenter: Alice Loft
Session: Poster Display session 2
Resources:
Abstract
2445 - Oncologic outcome of invasive lobular carcinoma: Is it different from that of invasive ductal carcinoma?
Presenter: Hee Jun Choi
Session: Poster Display session 2
Resources:
Abstract
2476 - Pathologic response and survival efficacy in patients with initial nodal involvement after neoadjuvant chemotherapy in early breast cancer
Presenter: SERAFIN MORALES Murillo
Session: Poster Display session 2
Resources:
Abstract
3761 - Chemotherapy-induced amenorrhea: prognostic impact on premenopausal Egyptian patients with breast cancer
Presenter: Khaled Abdel Karim
Session: Poster Display session 2
Resources:
Abstract
4687 - Predicting the presence of breast cancer using circulating small RNA in the serum
Presenter: Yumiko Koi
Session: Poster Display session 2
Resources:
Abstract