Cotinga Pharmaceuticals is seeking approval from the U.S. Food and Drug Administration (FDA) to expand its ongoing Phase 1 trial of COTI-2 to include combination therapies and a broader spectrum of cancer types.
The clinical trial (NCT02433626) is currently assessing the safety and tolerability of COTI-2 in patients with head and neck squamous cell carcinoma (HNSCC) and gynecological cancers. The company now plans to explore the experimental therapy alone or in combination with standard of care chemotherapeutics in multiple solid tumors.
Specifically, Cotinga hopes to expand the gynecological cancers part of the study to evaluate COTI-2 in combination with Avastin (bevacizumab) and Taxol (paclitaxel) or doxorubicin. In addition, COTI-2 will be tested in combination with Platinol (cisplatin) in HNSCC and other solid tumors.
Pending FDA approval, Cotinga anticipates the trial’s protocol could be changed by May.
The decision to change the protocol was supported by positive preliminary trial data and preclinical results demonstrating COTI-2’s positive interaction with chemotherapeutic drugs.
“After close consultation with our academic collaborators and investigators, we submitted a substantially updated regulatory package to the FDA seeking approval to evaluate COTI-2 as a combination therapy in our ongoing trial,” Alison Silva, president and CEO of Cotinga Pharmaceuticals, said in a press release.
“We look forward to implementing this amendment and dosing the first patient with a combination therapy regimen in the months ahead,” she said.
COTI-2 is a small molecule that acts on 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, so that p53 does not work properly.
Preclinical studies have shown that COTI-2 restores the activity of mutant p53 and induces cancer cell death. Together with low toxicity, the findings make COTI-2 an attractive therapeutic agent for many cancer types.
Interim clinical data from the first 24 patients with advanced gynecological cancers, including ovarian, fallopian tube, endometrial, and cervical cancer, showed that the therapy was safe overall and well-tolerated.
Participants received increasing doses of COTI-2 for a total treatment period of four weeks. The doses ranged from 0.25 mg/kg to 1.7 mg/kg.
Among the 15 evaluable patients, one achieved stable disease and five had progressive disease, but did not develop new lesions. Also, one patient had reduced levels of CA-125, an ovarian cancer biomarker.
The company will continue to analyze the results from this group of patients and expects to provide an update during the first quarter of 2018.
“The encouraging data readouts from the gynecological malignancies arm and the successful dosing of the first patient in our HNSCC expansion arm reinforce our confidence in COTI‐2 as a potential treatment for a range of oncology indications,” Silva said in a different press release.
The trial, conducted at the MD Anderson Cancer Center at the University of Texas, in Houston, and the Lurie Cancer Center at Northwestern University, in Chicago, currently is enrolling patients with HNSCC.
COTI-2 has received orphan drug designation by the FDA for the treatment of ovarian cancer.