Phase 1b Success: NGC-Cap Recommended for Phase 2 in Advanced Cancer Patients

Processa Pharmaceuticals, Inc., a clinical-stage pharmaceutical company, has announced the successful completion of the safety tolerability evaluation in its Phase 1b trial of Next Generation Capecitabine (NGC-Cap). The Phase 1b trial data has led to the selection of two dosage regimens for the upcoming Phase 2 trial, which will focus on advanced or metastatic breast cancer, following FDA's agreement that the Phase 1b data can be used to support the trial's design.

NGC-Cap is a combination therapy involving PCS6422 and capecitabine, a precursor to the cancer drug 5-FU. The treatment involves a single dose of PCS6422 administered 12-24 hours before a seven-day course of capecitabine, followed by a seven-day drug-free period. The Phase 1b trial evaluated various doses of capecitabine, ranging from 75 mg once daily to 225 mg twice daily.

The drug exposure to 5-FU for patients who received NGC-Cap treatment was significantly higher, 2-10 times more, than that of the FDA-approved capecitabine. Of the 18 patients who participated in the trial across four different dosing regimens, 16 completed at least two cycles of NGC-Cap. Notably, only one patient (6%) experienced a mild case of hand-foot-syndrome (HFS), a common side effect associated with 5-FU metabolite fluoro-beta-alanine (FBAL). This lower incidence of HFS is attributed to PCS6422's ability to inhibit the metabolism of 5-FU to FBAL, resulting in a significantly lower rate compared to FDA-approved capecitabine, where more than 50% of patients developed HFS.

In terms of myelosuppression, a condition that involves the decrease of cells that fight infections and help in clotting, the incidence rate for patients on the high dose of NGC-Cap (225 mg BID) was approximately 71%, with severe myelosuppression occurring in about 57% of the patients. This rate is comparable to the 80% rate reported for capecitabine. However, the rate of severe myelosuppression after the high dose of NGC-Cap was higher than the 3% rate reported for capecitabine. For the lower dose of NGC-Cap (150 mg BID), the incidence of myelosuppression was 33%, with no severe cases reported, which is lower than the rates associated with capecitabine.

Although the Phase 1b trial's primary objective was not to evaluate efficacy, preliminary data indicated that 80% of the 11 cancer patients who received one of the two highest doses of NGC-Cap showed a positive response. One patient had a partial response, and three demonstrated stable disease. Two additional patients are expected to become eligible for an efficacy evaluation by the end of the first quarter of 2024.

Processa's President of Research and Development, David Young, expressed gratitude to the participants of the trial and highlighted the significance of the findings. He noted that NGC-Cap was better tolerated than existing FDA-approved capecitabine, despite providing a greater exposure to the cancer-treating metabolite 5-FU. This suggests that NGC-Cap could potentially deliver more 5-FU to cancer cells, enhancing its cancer-killing effect.

Dr. Young further stated that NGC-Cap may offer a better efficacy profile with fewer side effects than currently prescribed capecitabine. If confirmed in subsequent studies, this could enable more patients to receive optimal doses of NGC-Cap without the need to reduce dosage or discontinue therapy due to tolerability issues. The Phase 1b trial data and FDA feedback have facilitated the development of a more efficient Phase 2 and 3 strategy, which is expected to lead to a higher likelihood of FDA approval as the company advances into advanced or metastatic breast cancer trials.

The Phase 1b study was a dose-escalation trial that aimed to assess the overall safety, pharmacokinetics, and anti-tumor activity of capecitabine in combination with PCS6422 (NGC-Cap) in 18 patients with advanced GI cancer. The primary goal was to estimate the recommended Phase 2 dose and the maximum tolerated dose. The most common adverse events related to treatment were myelosuppression, GI-related adverse events, and mucositis.

NGC-Cap is a novel approach to chemotherapy that combines the administration of PCS6422, an irreversible DPD enzyme inhibitor, with low doses of the widely used chemotherapy drug Capecitabine. Processa Pharmaceuticals is focused on developing Next Generation Chemotherapy (NGC) drugs to improve the safety and efficacy of cancer treatment. The company's approach leverages its Regulatory Science Approach and experience in defining Optimal Dosage Regimens for FDA approvals, aiming to provide better therapy options and increase the probability of FDA approval for its NGC drugs.

Processa Pharmaceuticals is currently developing three next-generation chemotherapy oncology treatments, including NGC-Cap, which is intended to treat a variety of cancers. The company's NGC drugs are modifications of existing FDA-approved oncology drugs, designed to alter metabolism and distribution while maintaining the existing mechanisms of killing cancer cells. The expected advantages of Processa's NGCs include fewer side effects, more significant cancer response, and a greater number of patients benefiting from each NGC drug.