Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 1

4264 - A Phase I study of tinostamustine in patients (pts) with advanced solid tumours

Date

28 Sep 2019

Session

Poster Display session 1

Presenters

Alain Mita

Citation

Annals of Oncology (2019) 30 (suppl_5): v159-v193. 10.1093/annonc/mdz244

Authors

A. Mita1, M. Loeffler2, N. Bui3, D. Remmy2, T. Mehrling2, M. Mita1, B.J. Rimel4, R.B. Natale1, S. Kummar5

Author affiliations

  • 1 Experimental Therapeutics, Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center, 90048 - Los Angeles/US
  • 2 Clinical Development, Mundipharma EDO GmbH, 4020 - Basel/CH
  • 3 Stanford Cancer Institute, Stanford University, 94305 - Stanford/US
  • 4 Obstetrics And Gynecology, Cedars-Sinai Medical Center, 90048 - West Hollywood/US
  • 5 Stanford Cancer Center, Stanford University, 94305 - Stanford/US
More

Resources

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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings