FDA Grants Fast Track Designation to ONC-392 for mNSCLC


Fast track designation has been granted by the FDA to ONC-392, an anti-CTLA-4 monoclonal antibody used for the investigational treatment of patients with metastatic non–small cell lung cancer.

The FDA has been granted fast track designation to ONC-392, a next-generation anti-CTLA-4 monoclonal antibody, for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) who have had disease progression on prior anti-PD-L1 therapy, according to a press release by ONcoC4, Inc.1

ONC-392 has the ability to preserve the CTLA-4 immune checkpoint function. The agent does not cause lysosomal degradation of CTLA-4, according to the developer. Currently, the agent is being evaluated in the phase 1 PRESERVE-001 clinical trial as monotherapy and with anti-PD-1 standard of care therapy in patients with advanced solid tumors including NSCLC.1,2

In the first-in-human, open-label phase 1A/1B study (NCT04140526), investigators are assessing the safety, pharmacokinetics, and efficacy of ONC-392 as a single-agent and in combination with pembrolizumab. (Keytruda) in patients with advanced solid tumor and NSCLC.2

In the first of 3 experimental arms, patients will receive single-agent ONC-391 by intravenous (IV) infusion, once every 21 days. In another arm, ONC-392 will be combined with IV pembrolizumab 200 mg per cycle, once every 21 days. In the third experimental arm, patients will be treated with ONC-392 in combination with osimertinib (Tagrisso) administered orally at 80 mg, once daily.

The coprimary end points of the study include the number of patients who experience a dose-limiting toxicity, determining the maximum-tolerated dose of ONC-392, determining the recommended phase 2 dose of the agent, and safety determined by the rate of treatment-related adverse events. The study will also investigate secondary end points including the serum half-life of ONC-392, the serum half-life of ONC-392 in combination with pembrolizumab, objective response rate, progression-free survival, and overall survival.

For enrollment, patients in part A are required to have a histologic or cytologic diagnosis of progressive and metastatic NSCLC, carcinoma, or sarcoma, or progressive and locally advanced disease that is not amenable to local therapy. For inclusion in part B, patients must have an advanced or metastatic solid tumor for which pembrolizumab is the standard of care therapy. Finally, for inclusion in part C, patients must have pancreatic cancer, triple-negative breast cancer, NSCLC, melanoma, Merkel cell carcinoma, head and neck cancer, ovarian cancer, and other solid tumors.

All patients enrolled in the study must have measurable disease, an ECOG performance score ≤ 2, adequate baseline laboratory tests, and adequate organ function.

Patients are ineligible for the study if they have been previously treated with an investigational therapy or device, had chronic steroid therapy at doses higher than 10 mg daily, or if they have comorbidities that may interfere with study treatment.

With a fast track designation, the developer of ONC-392 will get an expedited review of applications submitted to the FDA. The designation is intended for therapies will the potential to fill unmet medical needs.

“We are grateful for the Fast Track designation for ONC-392, which underscores the unmet need for new treatment options for patients with PD-L1-resistant NSCLC,” said Yang Liu, PhD, co-founder, chief executive officer, and chief scientific officer of OncoC4, in a press release. “We look forward to more frequent interactions with the FDA to accelerate our clinical development path as we seek to bring this promising drug candidate to patients as expeditiously as possible. Our phase 1b dose-expansion study is ongoing for multiple indications, including PD-L1-resistant NSCLC, with pivotal studies being planned in the near term.”


1. OncoC4 Announces fast track designation granted by the u.s. fda for onc-392 monotherapy in PD(L)1-resistant NSCLC. News release. April 26, 2022. Accessed April 26, 2022.

2. Safety, PK and efficacy of ONC-392 in monotherapy and in combination of anti-PD-1 in advanced solid tumors and NSCLC (PRESERVE-001). Clinicaltrials.gov. Updated January 11, 2022. Accessed April 26, 2022. https://bit.ly/3rWbybl

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