GEMMK
Research type
Research Study
Full title
A phase I study to assess the safety and tolerability of pembrolizumab in combination with fixed rate gemcitabine chemotherapy in patients with leiomyosarcoma and undifferentiated pleomorphic sarcoma
IRAS ID
209543
Contact name
Dr Robin Jones
Contact email
Sponsor organisation
The Royal Marsden NHS Foundation Trust
Eudract number
2016-004092-45
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Soft tissue sarcomas (STS) are a group of rare mesenchymal neoplasms affecting all ages. STS most commonly present as localised disease but despite surgery and adjuvant treatment more than half of patients will develop recurrent or metastatic disease. Leiomyosarcoma (LMS), a malignancy of smooth muscle, is one of the most common STS and undifferentiated pleomorphic sarcoma (UPS) is a common sarcoma sub-type with aggressive symptoms.
Recent studies have demonstrated reasonable sensitivity of LMS to gemcitabine monotherapy with an objective response rate of 8-19%. However the overall survival is still only about 12 months which illustrates the critical clinical need for improved therapies for advanced STS and sarcoma in general.
In this study we propose to combine the immune synapse checkpoint inhibitor with the cytotoxic and immune modulating agent, gemcitabine. It is hoped that this dual immunomodulatory approach will enhance the effect of pembrolizumab on PD-L1 expressing LMS and UPS, leading to a safe treatment with patient outcomes.
This is a two part, phase I, single centre dose escalation and dose expansion study in the total of 30 patients with newly diagnosed metastatic or inoperable LMS and UPS. There will be approximately 12 patients in the dose-escalation cohort (part A) and the starting dose will be a fixed dose rate (FDR) gemcitabine of 800 mg/m2 on day 1 and 8 of 21 days cycles in combination of 200 mg of pembrolizumab given as an infusion on day 1 every 3 weeks. The MTD cohort (part B) will then be expanded to a total of 12 patients in order to further evaluate the safety and tolerability of that dose as well as to preliminarily assess response to therapy.
The study is sponsored by Royal Marsden NHS Foundation trust and the funding for the study is provided by Merck Sharp & Dohme Limited.
REC name
London - Chelsea Research Ethics Committee
REC reference
17/LO/0767
Date of REC Opinion
22 Jun 2017
REC opinion
Further Information Favourable Opinion