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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

5550 - First-in-human study of the monopolar spindle 1 (Mps1) kinase inhibitor BAY 1161909 in combination with paclitaxel in subjects with advanced malignancies

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Clinical Research

Tumour Site

Presenters

Patricia Lorusso

Citation

Annals of Oncology (2018) 29 (suppl_8): viii133-viii148. 10.1093/annonc/mdy279

Authors

P. Lorusso1, S.P. Chawla2, J. Bendell3, A.F. Shields4, G. Shapiro5, P. Rajagopalan6, C. Cyris7, I. Bruns8, J. Mei8, F. Souza8, D. Rasco9, J.P. Eder1, A.W. Tolcher10

Author affiliations

  • 1 Yale Cancer Center, Yale University School of Medicine, 06520-8028 - New Haven/US
  • 2 Oncology, Sarcoma Oncology Research Center, 90403 - Santa Monica/US
  • 3 Gi Oncology Research, Sarah Cannon Research Institute/Tennessee Oncology, 37923 - Nashville/US
  • 4 Department Of Medicine, Karmanos Cancer Institute, 48201-2013 - Detroit/US
  • 5 Medical Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 6 Clinical Pharmacology, Bayer HealthCare Pharmaceuticals Inc, New York/US
  • 7 Clinical Statistics, Bayer HealthCare Pharmaceuticals Inc, New York/US
  • 8 Translational Medicine Oncology, Bayer HealthCare Pharmaceuticals Inc, New York/US
  • 9 Medical Oncology, START, San Antonio/US
  • 10 Clinical research, South Texas Accelerated Research Therapeutics (START) *Current affiliation: NEXT OncologyTM, 78229 - San Antonio/US
More

Resources

Abstract 5550

Background

Mps1 is a serine threonine kinase and a core component of the spindle assembly checkpoint. Two potent, selective, and orally active Mps1 inhibitors -- BAY 1161909 (BAY; lead compound) and BAY 1217389 -- have shown improved efficacy in combination with paclitaxel (Pac) in xenograft models, including Pac-insensitive and acquired resistance models. We report here on the safety, tolerability, and maximum tolerated dose (MTD) of the lead compound BAY in combination with Pac.

Methods

Subjects with advanced malignancies (solid tumors) and refractory to standard therapy were eligible. BAY was administered twice daily (BID) in a 2-days on/5-days off dosing schedule in combination with weekly IV Pac starting at 75 mg/m2 (Pac-75), and then at 90 mg/m2 (Pac-90). The dose of BAY was doubled in sequential cohorts until the MTD was reached. Pharmacokinetic analyses were done to determine exposure of BAY and Pac.

Results

A total of 37 patients were enrolled and treated in the Pac-75 cohort and 32 in the Pac-90 cohort, with median age 60 in both groups. Breast, NSCLC, and ovarian adenocarcinomas were the most common cancers. The majority of patients (53.6%) had >3 prior lines of anticancer therapy. BAY exposure generally increased in a dose proportional manner and did not affect Pac exposure. In BAY plus Pac-75 cohorts, 16% of patients had grade (G) 3 BAY-related adverse events (AEs), with no G4/G5 events. In the Pac-90 cohorts, 28% of patients had G3 events, one G4 and no G5 BAY-related events. The most common treatment emergent AEs were fatigue (44.9%), anemia (39.1%), alopecia (37.7%), diarrhea (34.8%) and nausea (33.3%). In 35 evaluable patients from the BAY plus Pac-75 group, there were 5 (14%) PRs, 11 SD,17 PD, and 2 patients not determined. In 28 evaluable patients in the BAY plus Pac-90 group, there were 4 (14%) PRs, 13 SD, and 11 PD. Six of 9 patients with a PR had prior Pac. One dose limiting toxicity (ALT increased) was reported in the BAY 180 mg BID plus Pac-90 dose cohort. The MTD was determined as BAY 90 mg BID plus Pac-90.

Conclusions

BAY in combination with Pac demonstrated good tolerability with manageable AEs and preliminary evidence of efficacy. Study with the follow-up compound BAY 1217389 is ongoing.

Clinical trial identification

NCT02138812.

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Editorial Acknowledgement

Disclosure

P. Rajagopalan, C. Cyris, I. Bruns, J. Mei, F. Souza: Employment: Bayer. All other authors have declared no conflicts of interest.

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