362PD - TAX-TORC: An investigator initiated phase I study combining the dual mTORC1/2 inhibitor AZD2014 in combination with weekly paclitaxel in high-grade...

Date 09 October 2016
Event ESMO 2016 Congress
Session Developmental therapeutics
Topics Clinical research
Basic Scientific Principles
Presenter Udai Banerji
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors U. Banerji1, B. Basu2, J.F. Spicer3, R. Wilson4, E. Hall1, R. Sundar1, S. Kumar5, Y. Wu3, V. Coyle4, S. Carreira1, M. Parmar1, J.C. Dawes1, S. Banerjee1, J.S. de Bono1
  • 1Drug Development Unit, Institute of Cancer Research ICR, SM2 5PT - London/GB
  • 2Oncology, Addenbrooke's Hospital University of Cambridge Hospitals, CB2 0QQ - Cambridge/GB
  • 3Department Of Medical Oncology, King's College London Guy's Hospital, SE1 9RT - London/GB
  • 4Centre For Cancer Research And Cell Biology, Queen's University Belfast, BT9 7JL - Belfast/GB
  • 5Oncology, Addenbrooke's Hospital University of Cambridge Hospitals, Cambridge/GB

Abstract

Background

We previously evaluated the tolerability of AZD2014 administered with weekly paclitaxel in 2 intermittent schedules. Based on the preliminary activity and preclinical data, we aimed to confirm tolerability in high-grade serous ovarian cancer (HGSOC), document preliminary efficacy and evaluate biomarkers of resistance and sensitivity.

Methods

Patients with HGSOC were treated with oral AZD2014 (50mg BD) for 3 days on/4 days off with weekly paclitaxel (80mg/m2) for 6 weeks of a 7 week cycle. Archival tumour samples are being assessed by targeted next-generation sequencing to identify potential biomarkers of sensitivity and resistance. Circulating plasma DNA assessments are being performed at baseline, at the end of cycle 1, at maximum response and at relapse.

Results

Currently 20/25 patients have been recruited with a median age of 67 years. The median number of previous treatments is 3 and 18/20 patients (90%) were platinum resistant or refractory prior to trial entry. Nineteen of the twenty patients (95%) received prior paclitaxel, of whom 3/20 (15%) received weekly paclitaxel. All 20 patients were assessed for toxicity; the most common grade 3-4 toxicities seen were vomiting (3/20), diarrhoea (2/20) and respiratory infections (2/20). There were 2 cases of pneumonitis (grades 1 and 3) and one case of bowel perforation which occurred at the site of metastatic infiltration, in the context of a rapidly reducing CA125 response. Twelve patients were evaluable for RECIST response at the end of cycle 1, after 6 weeks of combination therapy, 7/12 (58%) showed a partial response. Of 14 patients with evaluable CA125, 10 (71%) had a 50% reduction in baseline values. Of the patients that had previously received weekly paclitaxel, 2/3 (67%) had a CA125 response of greater than 50%. Biomarker analysis will be presented as the trial data matures.

Conclusions

The combination of the AZD2014 and paclitaxel is tolerable in patients with HGSOC. This schedule has shown promising preliminary efficacy in a population of patients pre-treated with a paclitaxel-containing regimen.

Clinical trial identification

EudraCT#2012-003896-20

Legal entity responsible for the study

Institute of Cancer Research and Royal Marsden NHS Foundation Trust

Funding

ECMC and AstraZeneca

Disclosure

All authors have declared no conflicts of interest.