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Developmental therapeutics

3758 - TAX-TORC: An investigator initiated phase I study combining the dual mTORC1/2 inhibitor AZD2014 in combination with weekly paclitaxel in high-grade serous ovarian cancer


09 Oct 2016


Developmental therapeutics


Udai Banerji


Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368


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

Author affiliations

  • 1 Drug Development Unit, Institute of Cancer Research ICR, SM2 5PT - London/GB
  • 2 Oncology, Addenbrooke's Hospital University of Cambridge Hospitals, CB2 0QQ - Cambridge/GB
  • 3 Department Of Medical Oncology, King's College London Guy's Hospital, SE1 9RT - London/GB
  • 4 Centre For Cancer Research And Cell Biology, Queen's University Belfast, BT9 7JL - Belfast/GB
  • 5 Oncology, Addenbrooke's Hospital University of Cambridge Hospitals, Cambridge/GB


Abstract 3758


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.


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.


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.


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


Legal entity responsible for the study

Institute of Cancer Research and Royal Marsden NHS Foundation Trust


ECMC and AstraZeneca


All authors have declared no conflicts of interest.

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