A new study is looking into the safety, tolerability, and preliminary efficacy of ZB131 in patients with advanced solid tumors.
The first patient has been dosed with ZB131 in a phase 1/2 study investigating the agent’s safety, tolerability, and preliminary efficacy in those with solid tumors who are non-responsive to or are ineligible for standard-of-care therapy, according to an announcement by ZielBio, Inc.1
ZB131, a monoclonal antibody, has a high affinity and specificity for a cell surface protein known as cancer specific plectin (CSP). CSP has been identified in a wide range of cancers, with a poor prognosis and tumors that aggressive.
"Having the first patient dosed in the ZB131 trial represents an important milestone for the company and for unserved patients, including those with cholangiocarcinoma, pancreatic, and ovarian cancers," said Kimberly Kelly, PhD, founder and chief executive officer of ZielBio, in a press release. "These types of cancers are difficult to treat with current therapies, but preclinical research suggests that ZB131 is able to bind to CSP located on the surface of cancer cells, resulting in profound tumor regression."
In the phase 1/2, first-in-human, open-label, dose-escalation study (NCT05074472), ZB131 will be administered by intravenous infusion at increasing dose levels with a starting dose of 3 mg/kg once weekly. The maximum dose that will be administered is 15 mg/kg once weekly.2
The primary end point of the phase 1 portion of the study is safety and tolerability. The phase 2 primary end point is establishing the recommended phase 2 dose. Upon determining the RP2D in phase 2, the trial will begin enrolling patients with cholangiocarcinoma, pancreatic cancer, and ovarian cancers for the dose-expansion stage.
A total 37 patients will be included in the study. To be eligible, patients must have a histological or cytological diagnosis of advanced solid tumors. All patients must also have an ECOG performance status of 0 to1; locally advanced, recurrent, or metastatic neoplastic disease; a life expectancy of ≥ 3 months; adequate laboratory values; and adequate hepatic function.
In the event that patients have undergone major surgery within 4 weeks of screening in the study, radiotherapy within 2 weeks, or have not recovered from radiation-related toxicities, they will be excluded from the study. Prior treatment with anti-cancer therapy, active central nervous system (CNS) metastases, and primary CNS malignancy are also grounds for exclusion from the study.
The study does not require screening for Hepatitis B or Hepatitis C. However, patients who received a live vaccine within 6 weeks of the first dose of ZB131 or a COVID-19 vaccine within 1 week of the first dose of ZB131 are not permitted to enroll. The study also excluded individuals with a history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis that requires steroid treatment, history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 6 months of study screening, and other conditions that may interfere with ZB131 treatment.
Patients who meet the inclusion criteria are actively being recruited at 3 centers in Texas and Virginia.
"The beginning of our clinical trial is an important step toward our goal of designing and offering safer, better therapies for patients who need them," said Brian Schwartz, MD, chief medical officer of ZielBio, in the press release.1 "By identifying new targets for treatment, we are expanding what is possible for the future of patient care and delivering new hope to a group of individuals who have not responded to or qualified for treatments previously."
1. ZielBio Announces first patient dosed in phase 1/2 clinical trial of ZB131, its novel monoclonal antibody targeting cancer specific plectin. News release. ZielBio, Inc. February 15, 2022. Accessed February 17, 2022. https://prn.to/3JAk2vf
2. A phase 1/2, first-in-human, open label, dose escalation study of a CSP targeting functional antibody in solid tumors. Clinicaltrials.gov. Accessed February 17, 2022.