Abstract 4264
Background
The novel multi-action alkylating deacetylase inhibitor tinostamustine (EDO-S101) has been shown in preclinical studies to improve drug access to DNA strands within cancer cells, break them, and counteract damage repair. Preclinical activity has been seen in models of solid tumours including sarcoma, small cell lung cancer, breast cancer, and ovarian cancer.
Methods
Patients (pts) with advanced solid tumours were recruited to an open-label phase I/II study to investigate the safety, pharmacokinetics and efficacy of tinostamustine (NCT03345485) using a standard 3 + 3 design. Six ascending cohorts received 60–100 mg/m2 tinostamustine IV over 30 or 60 minutes.
Results
The safety population contained 22 pts who had received a median of 5 lines of prior systemic therapy ± radiotherapy (mean ± SD age 59.7 ± 11.1 years, 40.9% male, 77.3% Caucasian, 22.7% Asian). Pts received a (mean ± SD) cumulative tinostamustine dose of 407.3 ± 218.44mg/m2 and spent 10.4 ± 8.6 weeks on therapy. All pts experienced ≥1 treatment-emergent adverse event (TEAE), the majority of which were mild or moderate in nature (nausea, 18/22 pts; QTc prolongation, 13/22 pts; thrombocytopenia, 12/22 pts; anaemia, 10/22 pts; lymphopenia, 9/22 pts; fatigue, 8/22 pts; vomiting and leukopenia, both 7/22 pts). Nausea and vomiting were well managed with antiemetics. Five pts experienced ≥1 serious TEAE, 3 of whom withdrew from the study. Only one pt experienced a clinically significant dose-limiting toxicity of Grade 3 QTc-prolongation following 100mg/m2 tinostamustine IV over 60 minutes. The RP2D is 80 mg/m2 IV over 60 minutes, which resulted in mean ± SD Cmax 1540 ± 852ng/ml and AUC0–t 1700 ± 913ng*h/ml on Days 15–16. Overall, 1/22 pts (diagnosis: endometrial cancer) achieved a partial response and 8/22 pts stable disease (SD); 4/8 pts who received the RP2D achieved SD.
Conclusions
Tinostamustine was generally well tolerated in patients with advanced solid tumours and limited treatment options. The phase II portion of this study will further investigate the efficacy of the RP2D of 80 mg/m2 tinostamustine IV over 60 minutes in SCLC, triple-negative breast cancer, soft tissue sarcoma, ovarian cancer, and endometrial cancer. Funding: Mundipharma EDO GmbH.
Clinical trial identification
NCT03345485.
Editorial acknowledgement
Editorial support (in the form of writing assistance, collating author comments, grammatical editing and referencing) was provided by Sarah Birch, PhD, at Makara Health Communications Ltd., UK and was funded by Mundibiopharma Ltd.
Legal entity responsible for the study
Mundipharma EDO GmbH.
Funding
Mundipharma EDO GmbH.
Disclosure
M. Loeffler: Full / Part-time employment: Mundipharma EDO. D. Remmy: Full / Part-time employment: Mundipharma EDO. T. Mehrling: Leadership role, Full / Part-time employment: Mundipharma EDO. S. Kummar: Advisory / Consultancy: Mundipharma EDO. All other authors have declared no conflicts of interest.
Resources from the same session
2831 - Interleukin-6 as a Predictive Marker for Early Response to Induction Chemotherapy in Acute Myeloblastic Leukaemia
Presenter: Salah Khallaf
Session: Poster Display session 1
Resources:
Abstract
6014 - Impact of FLT3-ITD mutation on post-transplant outcome of adult AML is modified by the concomitant NPM1 mutation and pre-transplant remission status: A report from Taiwan Bone Marrow Transplant Registry (TBMTR)
Presenter: Su-peng Yeh
Session: Poster Display session 1
Resources:
Abstract
2914 - Efficacy endpoints studied in clinical trials for early-onset leukaemia
Presenter: Dylan Said
Session: Poster Display session 1
Resources:
Abstract
4691 - High triglyceride is a major risk factor of DIC and differentiation syndrome in acute promyelocytic leukemia
Presenter: Tomohiro Yamakawa
Session: Poster Display session 1
Resources:
Abstract
4395 - DREAMM 4: A Phase I/II single-arm open-label study to explore safety and clinical activity of belantamab mafodotin (GSK2857916) administered in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM)
Presenter: Suzanne Trudel
Session: Poster Display session 1
Resources:
Abstract
2808 - A Phase 1 Study of HMPL-523, a Selective Oral Anti-Spleen Tyrosine Kinase Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Nathan Fowler
Session: Poster Display session 1
Resources:
Abstract
4403 - A Phase 1 Study of HMPL-689, a Selective Oral Phosphoinositide 3-Kinase-Delta Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Jonathon Cohen
Session: Poster Display session 1
Resources:
Abstract
3357 - A global patient-driven Facebook study in a very rare sarcoma: Health-related quality of life in Epithelioid Hemangioendothelioma (EHE) patients
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
2475 - Qualitative study of patients’ experiences of living with and beyond a soft tissue sarcoma diagnosis: the impact of sarcoma specialist services
Presenter: Ana Martins
Session: Poster Display session 1
Resources:
Abstract
2640 - Health-related quality of life issues of patients affected by desmoid-type fibromatosis; experiences from two countries
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract