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W. Lam
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-025 - DREAM - A Phase 2 Trial of DuRvalumab with First Line chEmotherApy in Mesothelioma with a Safety Run In (ID 4412)
14:30 - 14:30 | Author(s): W. Lam
- Abstract
Background:
Immunotherapy is active in malignant pleural mesothelioma (MPM). Durvalumab is a human monoclonal antibody directed against the programmed cell death ligand 1 (PD-L1). We hypothesize that the addition of durvalumab to first-line chemotherapy improves 6-month progression free survival (PFS6).
Methods:
DESIGN: Open-label, single arm, multi-centre, phase 2 trial with a safety run in. ELIGIBILITY: Adults with MPM starting first-line cisplatin and pemetrexed. ENDPOINTS: PFS6 (primary) and objective tumour response rate using modified RECIST for MPM and modified immune-related response criteria; adverse events and overall survival. Tertiary correlative objectives include associations between potential predictive/prognostic biomarkers and clinical outcomes. TREATMENT: Durvalumab 1125mg (dose to be confirmed in safety run-in), cisplatin (75mg/m[2]) and pemetrexed (500mg/m[2]) 3-weekly for a maximum of 6 cycles, followed by durvalumab alone until progression or for a maximum of an addition of 12 cycles. STATISTICS: 6 participants in an initial safety run-in using a 3+3 design, will be included in the total sample size of 54 evaluable participants, consisting of 31 recruited in stage 1, and another 23 in stage 2. The null hypothesis is that the true PFS6 rate is 45%, in keeping with standard therapy and would be considered not worthy of further evaluation. The two-stage design provides greater than 90% power with a one-sided type I error rate of 5% if the true PFS6 rate is 65% (alternate hypothesis). ASSESSMENT: CT scans 6-weekly for the first 30 weeks, then 9-weekly until disease progression. Translational research blood collections: baseline, cycle 2 and 3.
Results:
Central ethics submission has been completed and recruitment will be updated.
Conclusion:
DREAM is an investigator-initiated cooperative-group trial led by ALTG, in collaboration with NHMRC Clinical Trials Centre, University of Sydney, with support from Astra-Zeneca.
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P2.06-026 - A Phase II Trial of the Oral FGF Receptor Inhibitor AZD4547 as 2nd or 3rd Line Therapy in Malignant Pleural Mesothelioma - Trial in Progress (ID 4417)
14:30 - 14:30 | Author(s): W. Lam
- Abstract
Background:
Dysregulation of the fibroblast growth factor (FGF) pathway is observed in a variety of cancers, including mesothelioma. FGF-9 is significantly over-expressed in mesothelioma and our pre-clinical data demonstrates that inhibition of FGF receptor (FGFR)-mediated signalling in vitro results in anti-proliferative and pro-apoptic activity. FGFR-targeted tyrosine kinase inhibitors strikingly reduce tumour burden in three separate murine models of mesothelioma. AZD4547 is a potent and selective oral FGFR-1,2, and 3 tyrosine kinase inhibitor that inhibits FGFR-related signal transduction pathways which makes AZD4547 appropriate to test in MPM in the context of strong preclinical rationale.Common side effects include dry mouth, mucositis and dermatological toxicity. Serious side effects include ophthalmological toxicity, such as Retinal Pigmented Epithelium Detachment (RPED), conjunctivitis and corneal atrophy, hyperphosphatemia leading to cardiac mineralisation and renal failure.
Methods:
The study is an open-label single centre phase II trial of single-agent oral AZD4547 in patients with confirmed, measurable MPM who have progressed after 1[st] or 2[nd] line chemotherapy. Key inclusion/exclusion criteria include ECOG performance status 0-1; adequate organ function; and drug-specific ophthalmological and cardiac exclusion criteria. The primary endpoint is 6 month progression-free survival (PFS-6), with secondary end points of objective tumour response (modified RECIST), PFS, overall survival, toxicity and treatment duration. We will enrol 26 patients in the first of 2 stages (Simon 2-stage design). If more than 7 of the first 26 have PFS >6 months, we will continue to a total of 55 patients. Observing a total of 50 progression events will provide 90% power to identify a 6 month PFS of >45%. Correlative biomarkers including immunological biomarkers from blood and pleural fluid will also be collected. These will be correlated with disease activity, effects of study drug and clinical outcomes to detect any biomarkers and potential predictive biomarkers.
Results:
As of 1[st] July 2016, 7 patients have been enrolled and recruitment is ongoing. There have been no grade 3 or 4 toxicities and no cardiac or ophthalmological toxicities. Main toxicities are grade 1 mucositis and dry mouth. 1 patient had hyperphosphatemia which resolved with dietary modification.
Conclusion:
AZD4547 is well tolerated with no grade 3 or 4 toxicities shown at this stage in a small number of patients. Recruitment commenced in April 2016 and stage 1 is projected to be completed by April 2017.
