1st Patient Dosed in Phase 1/2 Trial of COTI-2 Plus Chemo for Gynecological and Other Solid Cancers

A first patient has been given a combination of an investigational therapy, COTI-2, plus standard-of-care chemotherapy in an expanded Phase 1b/2a trial for gynecological and other solid tumors, Cotinga Pharmaceuticals, the potential treatment’s developer, announced.

The clinical trial (NCT02433626) was first designed to evaluate the safety and efficacy of COTI-2 alone in advanced and recurrent gynecologic and head and neck cancers. But after preliminary trial data and preclinical results showing COTI-2’s positive interaction with chemotherapeutic drugs, the company expanded the trial to include combinations of COTI-2 and standard of care chemotherapies.

“We are pleased with the progress we have made in dosing of cohort 1 patients in our COTI-2 plus cisplatin combination trial,” Alison Silva, Cotinga’s president and CEO, said in press release. “We are hopeful that combining existing chemotherapy regimens with COTI-2 could be a potential treatment.”

COTI-2 is a small molecule that acts on the mutated p53 protein to prevent tumor progression. p53 is a natural tumor suppressor that cells use to prevent uncontrolled cell growth. But in over 50 percent of all cancers, the gene that encodes this protein is mutated, preventing p53 from working properly.

Preclinical studies have shown that COTI-2 restores the workings of mutant p53 to induce cancer cell death. Together with low toxicity, the findings make COTI-2 a potentially attractive therapy for many cancer types.

The trial was initially composed of two parts, each designed to determine the best and safest dose for patients with gynecological cancers — ovarian, fallopian tube, primary peritoneal, endometrial, or cervical cancer — or for those with head and neck squamous cell carcinoma.

Interim clinical data from the trial’s first part found that COTI-2 alone is generally safe and well-tolerated. It also provided evidence of early efficacy, with one patient achieving stable disease and a second lower levels of CA-125, an ovarian cancer biomarker.

With the protocol amendment, the trial now includes a third group of patients who will receive COTI-2 in combination with Platinol (cisplatin). This part will include 30 patients with solid cancers, including ovarian, fallopian tube, primary peritoneal, endometrial, cervical, lung, pancreatic or colorectal cancer, or head and neck squamous cell carcinoma.

Patients will take COTI-2 orally, in a five-days-on, two-days-off schedule until they no longer benefit from the treatment. Platinol will be given as an infusion once every three weeks.

Safety and efficacy assessments will be performed every six weeks to determine the optimal, maximum tolerated dose of COTI-2 to be used in Phase 2 of the trial. COTI-2’s stability and overall distribution in the body will also be examined.

Eligible patients are being recruited at the study’s one site, MD Anderson Cancer Center in Houston. More information is available here.

“We remain committed to advancing the clinical development of COTI-2, and we will continue to provide key updates as the trial progresses,” Silva said.