Initial data from an early clinical trial in patients with advanced ovarian and other cancers found a potential oral therapy, COTI-2, to be safe at varying doses, supporting a more advanced Phase 2 trial in these people, Critical Outcome Technologies announced.

“We are encouraged to see these PK [pharmacokinetic] data from our Phase 1 trial in gynecological malignancies,” Alison Silva, president and chief executive officer of Critical Outcome Technologies, said in a press release. “These promising PK signals … reinforce our commitment to the continued advancement of COTI-2 through clinical development.

COTI-2 is a novel small molecule that acts on the TP53 gene – a major tumor suppressor protein. TP53 is often mutated in cancer and contributes to metastasis and drug resistance in these cells. COTI-2 is designed to act on mutated p53 to make it function more as a normal, wild-type protein, helping to suppress cancer growth and spread.

The Phase 1 study (NCT02433626) is assessing the safety and tolerability of COTI-2 in patients with advanced and recurrent gynecologic cancers, and head and neck cancers. The trial, which began in late 2015 and ends in December 2018, also aims to identify the maximum tolerated dose for further Phase 2 studies.

Secondary endpoints included patients’ clinical response and progression-free survival.

The trial has recruited 24 patients with ­several different types of cancer — including ovarian, fallopian tube, endometrial, and cervical cancer — all in advanced stages (recurrent, metastatic, or unresectable). Patients received escalating doses of COTI-2 — from 0.25 mg/kg to 1.7 mg/kg — administered orally in four-week cycles of five treatment days per week. All doses tested, including the highest dose of 1.7 mg, were safe and well-tolerated.

Pharmacokinetic data showed the therapy was rapidly absorbed, taking eight to 10 hours for its peaks to drop to half once administered — a measure known as half-life. This pharmacokinetic profile is in agreement with the therapeutic dynamics shown in preclinical studies for gynecological cancers.

The therapy is continuously eliminated from the body, with total clearance taking approximately one week.

Patients with head and neck squamous cell carcinoma are still being enrolled, and top-line results are expected in late 2018.

The Phase 1 trial is being conducted at the MD Anderson Cancer Center at the University of Texas (Houston) and the Lurie Cancer Center at Northwestern University in Chicago, and both are enrolling patients. Those interested can find more information on the study’s clinical trials.gov page.

“We look forward to updating you on further progress in this trial as we continue to analyze secondary and exploratory endpoint data from the gynecological arm and enroll patients in the head and neck squamous cell carcinoma (HNSCC) expansion arm,” Silva added.

“As part of our analyses, we found the half-life of COTI-2 was substantially longer than other treatments targeting mutant p53,” said Richard Ho, the company’s chief scientific officer. “Combined with our data suggesting rapid absorption and lack of long-term drug accumulation, our findings support the potential for daily oral dosing of COTI-2, a crucial advantage for our compound.”