Mundipharma EDO GmbH (EDO) has begun a US Phase 1/2 clinical study for tinostamustine (EDO-S101) in patients with advanced solid tumors at Stanford University, Cedars Sinai Medical Center (Los Angeles) and The Mayo Clinic (Scottsdale). The news follows the announcement last year of the first-in-human study for tinostamustine in relapsed/refractory hematological malignancies.
The initial phase of the new study has been designed to determine the safety, tolerability, maximum dose and optimal dosing schedule of tinostamustine as a single agent in patients with solid tumors, who have progressed after at least one line of therapy and no other standard therapy with proven clinical benefit is available. It will also investigate the pharmacokinetic profile. The study will then expand to evaluate toxicity and response rates in selected relapsed/refractory solid tumors including: small cell lung cancer (SCLC); soft tissue sarcoma (STS) or non-KIT gastrointestinal stromal tumors (GIST); triple negative breast cancer (TNBC); and ovarian cancer.
Although an effective option for some cancer patients, traditional DNA-damaging therapies have certain limitations which can result in resistance, for example, a failure to gain access to the DNA strands to break them or an inability to counteract the DNA repair mechanisms within cancer cells.
Tinostamustine (EDO-S101) is an AK-DACi (a first-in-class alkylating deacetylase inhibiting molecule) that, in preclinical studies, has been shown to improve access to the DNA strands within cancer cells, break them and counteract damage repair. Preclinical studies suggest that these complementary and simultaneous modes of action have the potential to overcome resistance.,
Preclinical experiments in solid tumors show that tinostamustine exhibits efficacy in most SCLC cell lines, including those that are resistant to doxorubicin., Activity has also been established in
preclinical studies for STS, TNBC and ovarian cancer.
Dr. Thomas Mehrling, CEO of EDO said: “Following the initial Phase 1 study in hematological malignancies, I am delighted that EDO is now embarking on a further clinical trial in solid tumors. People with advanced solid tumors can become resistant to treatment and often have a relatively poor chance of survival. Breaking through resistance is essential if we are to continue to address unmet needs in oncology. This is a key step in the investigation of a first-in-class treatment, which we hope will prove a vital addition for patients with limited current options.”