The study will be conducted in two parts. The first part of the study will focus on determining the safety, tolerability, maximum dose, and optimal dosing schedule of tinostamustine as primary objectives. The drug will be evaluated as a single agent in patients with solid tumors that have progressed after at least one line of therapy and where there is no other therapy available.
This part of the trial will also determine how the drug behaves in the body, and how gene expression changes in tumors that respond to tinostamustine.
The second part of the study will evaluate toxicity and response rates in selected relapsed/refractory solid tumors, primarily in triple negative breast cancer, ovarian cancer, small cell lung cancer (SCLC), and a few others. The primary goals will be assessing the objective response rate (ORR) and clinical benefit rate (CBR).
It will also determine the drug’s safety, progression-free survival, overall survival, and duration of response.
“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,” Thomas Mehrling, chief executive officer of Mundipharma EDO, said in a press release.
“People with advanced solid tumors can become resistant to treatment and often have a relatively poor chance of survival,” he said. “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.”
Tinostamustine is a first-in-class alkylating deacetylase inhibiting molecule (AK-DACi) that has been shown in preclinical studies to improve access to the DNA strands within cancer cells, breaking and counteracting repair mechanisms.
Studies have suggested that these complementary, simultaneous modes of action could potentially overcome resistance, which can happen with traditional DNA-damaging therapies.
In these studies, preclinical experiments in solid tumors have also reportedly shown that tinostamustine is active against TNBC and ovarian cancer.
Because triple negative breast cancer is not a good candidate for hormone therapy or HER2-targeted therapies, tinostamustine could hold significant therapeutic potential. TNBC tends to be more aggressive than other types of breast cancer, and is more likely to spread beyond the breast tissue (metastasize) and recur after treatment.