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
4250 - Phase II study of avelumab in combination with cetuximab as a rechallenge strategy in pre-treated RAS wild type metastatic colorectal cancer patients: CAVE (cetuximab-avelumab) Colon.
Presenter: Erika Martinelli
Session: Poster Display session 2
Resources:
Abstract
5234 - The ORCHESTRA trial; A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).
Presenter: Lotte Bakkerus
Session: Poster Display session 2
Resources:
Abstract
5294 - EMERGE: Epigenetic Modulation of the Immune Response in Gastrointestinal cancers
Presenter: Elizabeth Cartwright
Session: Poster Display session 2
Resources:
Abstract
913 - Phase III, international, multicenter, randomized, open-label trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) alone for surgically resected pancreatic adenocarcinoma (APACT): subgroup analyses
Presenter: Margaret Tempero
Session: Poster Display session 2
Resources:
Abstract
1668 - FOLFIRINOX in locally advanced (LA) and borderline resectable (BR) pancreatic adenocarcinoma : update of the AGEO cohort.
Presenter: Edouard Auclin
Session: Poster Display session 2
Resources:
Abstract
2559 - Impact of adjuvant treatment with nab-paclitaxel and gemcitabine (nab-P+GEM) vs gemcitabine alone (GEM) on health-related quality of life (QoL) in patients (pts) with surgically resected pancreatic adenocarcinoma (PA) in the Adjuvant Pancreatic Adenocarcinoma Clinical Trial (APACT)
Presenter: Hanno Riess
Session: Poster Display session 2
Resources:
Abstract
4897 - Early detection of pancreatic ductal adenocarcinoma using methylation signatures in circulating tumor DNA
Presenter: Xiao-ding Liu
Session: Poster Display session 2
Resources:
Abstract
1755 - Evaluation of minimal important difference (MID) for the European Organisation for Research and Treatment of Cancer (EORTC) Pancreatic Cancer Module (PAN26) in patients with surgically resected pancreatic adenocarcinoma
Presenter: Michele Reni
Session: Poster Display session 2
Resources:
Abstract
2876 - Multispectral analysis of lymphocyte complexity in periampullary adenocarcinoma
Presenter: Sebastian Lundgren
Session: Poster Display session 2
Resources:
Abstract
1902 - Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)
Presenter: Jae Ho Jeong
Session: Poster Display session 2
Resources:
Abstract