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Clinical Trial Summary

HyPeR is a multi-centre Phase 1 Dose Escalation Study of Guadecitabine (SGI-110) a Second Generation Hypo-Methylating Agent in Combination with Pembrolizumab (MK3475) in Patients with Refractory Solid Tumours. The investigators will be investigating the safety and toxicity of the combination.

Clinical Trial Description

This is a phase I trial of the combination of the hypo-methylating agent guadecitabine and an anti-PD1 antibody (anti- programmed cell death protein 1) pembrolizumab. Patients will receive subcutaneous guadecitabine daily on Days 1-4 of each 21-day cycle. Patients will receive pembrolizumab intravenously once per 21-day cycle: on Day 8 of Cycle 2 and on Day 1 of each cycle from Cycle 3 onwards. The rational for this design is that this pre-loading with Guadecitabine will sensitise the tumour to Pembrolizumab through the re-expression of genes that enhance tumour recognition, the increase in density of tumour infiltrating T-cells and stimulation of the adaptive immune response. In Part A (Dose Escalation) the investigators will investigate escalating doses of Guadecitabine in combination with Pembrolizumab. Patients with advanced solid tumours will be recruited in cohorts of 3 to 6 patients to investigate the combination of 200 mg of pembrolizumab, administered as an intravenous injection, with escalating doses of guadecitabine, administered via a subcutaneous injection, once a day for 4 days (Days 1-4). Guadecitabine dosing will start at 45mg/m2 but can be decreased to 30mg/m2 in the event of toxicities or increased to 60mg/m2 in the absence of toxicities. Once the maximum tolerated dose is reached (or under the advice from the Safety Review Committee) patients will be enrolled to the dose expansion phase (Part B). Part B (Dose Expansion): 20 patients will be recruited to Part B to further explore the safety and activity of the combination of guadecitabine and pembrolizumab. This cohort will include, but not be limited to patients with: castration resistant prostate cancer (CRPC), non-small cell lung cancer (NSCLC) and possibly other solid tumours based on emerging anti-tumour activity data from Part A and any other relevant preclinical or clinical published data. Approximately 30 to 35 patients will be entered into this trial, 6 to 12 patients in Part A and 20 patients in Part B. The anticipated accrual rate of the dose escalation phase will involve approximately 3 patients per month across 2 centres. Accrual rates could be higher or lower but this estimate takes into consideration that the first patient on an escalation cohort should complete Cycle 2 Day 15 prior to accrual of further patients in the cohort. Accrual in the expansion phase is estimated at 2-4 patients per month across 2 centres. It is expected that the duration of recruitment will be 12-24 months. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT02998567
Study type Interventional
Source Royal Marsden NHS Foundation Trust
Status Active, not recruiting
Phase Phase 1
Start date January 26, 2017
Completion date June 2021

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