Villejuif, 3 june 2016
Two promising early trials presented at ASCO 2016
Gustave Roussy early trials are conducted by the Drug Development Department (DITEP). «Our mission is to offer access to new agents to patients in whom therapy has failed» states Professor Jean-Charles Soria, Head of the Department. DITEP currently has 15 early trials in Haematology ongoing.
The promising results of two of these will be presented on Friday 3rd and Monday 6th June.
The first uses an approach combining a targeted therapy with known therapies in refractory and/or relapsed multiple myeloma. The second examines a new immunotherapeutic agent in T-cell lymphoma. «Of the main priority areas currently under development in Haematology, immunotherapy is clearly one of the two key approaches, the other being epigenetics» comments Dr. Vincent Ribrag, DITEP Haematologist.
Evaluating the synergistic effects of a new targeted therapy administered in conjunction with two known therapies in relapsed multiple myeloma
Triple combinations (Bortezomib, Thalidomide/Lenalidomide, and Dexamethasone) have increased life expectancy. Despite continuing substantial increases in efficacy, 50% of patients will have progressive disease within the 2 years following their first treatment. The duration of response to second-line drugs is shorter. This disease, for which life expectancy is increasing in parallel with advances in therapy, is tending to become a chronic condition.
More than 100,000 individuals are now living with myeloma in the United States. New drugs such as plitidepsin, acting on new molecular pathways, are being offered in early trials for patients who have refractory disease or are in relapse.
In a phase I clinical trial conducted by DITEP, the activity and safety profile of plitidepsin combined with bortezomib and dexamethasone (two drugs which are currently indicated in treatment of multiple myeloma), were studied in patients with relapsed and/or refractory myeloma. Plitidepsin represents a new therapeutic class, targeting the eEF1A2 protein which is overexpressed in myeloma.
Previous pre-clinical and phase 1/2 clinical trials of plitidepsin combined with known therapies (bortezomib/lenalidomide and dexamethasone) had shown promising results. This trial’s objective was to determine the recommended dose in use, the pharmacokinetics and the safety profile of the combination therapy.
Drs. Vincent Ribrag and Jean-Marie Michot, DITEP Haematologists, are co-authors of a presentation of the early results of the trial, APL-A-012-13, in 20 patients. The objective response rate is 56%, including 2 complete responses (11%) and 4 very good partial responses (22%). This trial established a recommended dose in use of 5 mg/m2 for plitidepsin administered every 4 weeks in combination with dexamethasone 40 mg and bortezomib 1.3 mg/m2 on a day 1, 4, 8 and 11 schedule.
> Read the abstract: Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma.
Study of a new antibody directed against CD70
T-cell lymphoma is a very specific entity amongst the non-Hodgkin’s lymphomas (NHL). Epidemiologically, its distribution is uneven: whereas it comprises 10% of NHL in the “West” (United States and Europe), it constitutes 25% in the “East” (Asia). Unfortunately, its prognosis is much worse than that of B-cell lymphomas. Novel chemotherapies for it are very much hoped for.
In another phase I study, Dr. Vincent Ribrag is presenting efficacy and safety data on ARGX-110. This antibody targets CD70, an antigen expressed on the cell surface in some malignant disorders (T-cell lymphomas in particular).
It has been tested in 9 patients with CD70-positive T-cell lymphoma and has displayed safety in use and anti-tumour biological activity manifest as a reduction in biomarkers (circulating tumour clone). These data are in favour of clinical development of ARGX-110 in T-cell lymphoma.
> Read the abstract: Clinical response observed in a phase i study in t cell lymphoma patients treated with anti-cD70 simple antibody™ argx-110.