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
5638 - Incidence of Vascular Thromboembolism Events in Cancer Patients Receiving Immunotherapy: A Single Institution Experience.
Presenter: Laura Gutiérrez Sainz
Session: Poster Display session 1
Resources:
Abstract
5182 - High Incidence of Venous Thromboembolic Events (VTE) in Patients with Diffuse Large B-Cell Lymphoma.
Presenter: Alaa Abufara
Session: Poster Display session 1
Resources:
Abstract
1504 - Weight Loss over Time in Non-Small Cell Lung Cancer: Results from a Landmark Analysis of 800+ Prospectively-Treated Patients
Presenter: Jennifer Le-rademacher
Session: Poster Display session 1
Resources:
Abstract
3972 - The prognostic significance of preoperative nutritional status in resected pancreatic ductal adenocarcinoma (PDAC).
Presenter: Salvatore Paiella
Session: Poster Display session 1
Resources:
Abstract
2313 - Impact of Timing and Technique of Gastrostomy Placement on the Outcome of Patients (pts) with Head and Neck Cancer (HNC)
Presenter: M Julia Lostes Bardaji
Session: Poster Display session 1
Resources:
Abstract
5219 - Clinical & nutritional determinants of quality of life in patients with incurable cancer
Presenter: Louise Daly
Session: Poster Display session 1
Resources:
Abstract
4075 - Loss of skeletal muscle mass during palliative chemotherapy is a poor prognostic factor in patients with advanced gastric cancer
Presenter: In Gyu Hwang
Session: Poster Display session 1
Resources:
Abstract
4159 - Impact of nutritional derangement on treatment outcome in advanced non-small-cell lung cancer (A-NSCLC) patients (pts).
Presenter: Ilaria Trestini
Session: Poster Display session 1
Resources:
Abstract
1210 - Sarcopenia and pretreatment anemia as prognostic factors for patients with localized muscle invasive bladder cancer treated by neoadjuvant chemotherapy and radical cystectomy
Presenter: Emilien Billon
Session: Poster Display session 1
Resources:
Abstract
2490 - Gender effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of anamorelin (ANAM) in healthy volunteers and cancer patients with cachexia
Presenter: Stein Kaasa
Session: Poster Display session 1
Resources:
Abstract