Hanmi Pharmaceutical's New Drug Demonstrates Excellent Efficacy in Research Presented at European Society for Medical Oncology

Hanmi Pharm Headquarters Exterior (Photo by Hanmi Pharm)

[Asia Economy Reporter Chunhee Lee] Research results on the excellent efficacy of the anticancer new drugs 'Belvarafenib' and 'Poziotinib,' licensed out by Hanmi Pharmaceutical, were presented at the European Society for Medical Oncology (ESMO).

Hanmi Pharmaceutical announced on the 23rd that major research results of anticancer new drugs developed and licensed out by Hanmi, including Belvarafenib and Poziotinib, were presented at the 2021 European Society for Medical Oncology (2021 ESMO Virtual Congress), held online from the 16th to the 21st. Hanmi Pharmaceutical has licensed Belvarafenib to Genentech, a Roche affiliate, and Poziotinib to Spectrum Pharmaceuticals in the United States.

At this ESMO, clinical results of Belvarafenib, a selective RAF mutation inhibitor developed by Hanmi Pharmaceutical, led by Professor Taewon Kim of the Department of Oncology at Seoul Asan Medical Center, were disclosed. The study confirmed improved safety and antitumor effects through a phase 1b clinical trial combining Belvarafenib with a MEK inhibitor (Cobimetinib) in patients with solid tumors harboring RAF or RAS mutations.

RAS is an oncogenic tumor gene protein that plays an important role in growth, proliferation, and apoptosis in normal cells but can cause uncontrolled proliferation of tumor cells when mutated. RAF is a downstream signaling protein of RAS that mediates intracellular signal transduction.

According to the results of this study involving a total of 118 patients, the tolerability of the combination therapy was excellent, and safety was consistent with that of each individual drug. Most notably, promising antitumor effects were observed in N-RAS (RAS subtype) and B-RAF (RAF subtype) melanomas as well as B-RAF class 2/3 (atypical) mutation cancers.

Among 19 patients with N-RAS mutant melanoma, 5 (26.3%) showed partial response (PR), and 8 (42.1%) achieved stable disease (SD). All patients who showed partial response had a history of prior immunosuppressive therapy. The median progression-free survival (PFS) was 7.3 months.

Among 5 patients with B-RAF atypical mutation melanoma, 3 (60%) showed partial response, and 2 achieved stable disease. Both patients with B-RAF atypical mutation non-small cell lung cancer showed partial response.

Adverse reactions included dermatitis (52.5%), diarrhea (28.0%), rash (27.1%), and increased creatine phosphokinase (CPK) levels (25.4%). More than half of the patients experienced temporary discontinuation of Belvarafenib or MEK inhibitor, but permanent discontinuation was rare. No pharmacokinetic interactions between the two drugs were observed.

Meanwhile, Spectrum Pharmaceuticals announced additional clinical data from cohort 4 of the global ZENITH20 clinical trial for Poziotinib, which is being developed as a lung cancer drug. This clinical trial was listed in the latest clinical research list of ESMO.

Poziotinib was designated as a fast-track development drug by the U.S. Food and Drug Administration (FDA) earlier this year, and a new drug application (NDA) is expected to be submitted to the FDA by the end of this year.

The phase 2 ZENITH20 trial for non-small cell lung cancer patients is divided into seven cohorts. The presented results are from cohort 4, which involves patients with HER2 exon 20 insertion mutations who have no prior treatment history.

Poziotinib 16 mg was administered orally once daily, allowing dose interruptions and reductions due to toxicity, and patients were followed for 24 months. The primary endpoint was objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by an independent central review committee (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and safety.

According to the study results, among 48 patients, the ORR was 44%, with one patient achieving complete remission (CR) of non-small cell lung cancer. Tumor reduction was observed in 42 patients (88%). Secondary endpoints recorded a DCR of 75%, median DoR of 5.4 months, and median PFS of 5.6 months.

The most common treatment-related grade 3 or higher adverse events (AEs) were rash (35%), stomatitis (20%), diarrhea (14%), and paronychia (8%). The safety profile was manageable and similar to other second-generation tyrosine kinase inhibitors (TKIs). Spectrum is also conducting patient enrollment and clinical trials for a study administering Poziotinib 8 mg twice daily.

Another partner of Hanmi Pharmaceutical, Anetex, also disclosed interim results of a phase 1 clinical trial at this ESMO, confirming the safety, tolerability, and antitumor effects of the oral anticancer drug 'Oraxol' developed by Hanmi Pharmaceutical in combination with a PD-1 immune checkpoint inhibitor in patients with advanced solid tumors.

Sechang Kwon, President of Hanmi Pharmaceutical, said, “The innovative anticancer drugs licensed out by Hanmi Pharmaceutical are progressing smoothly based on encouraging clinical results. We will do our best to rapidly commercialize innovative new drugs for patients suffering from cancer.”