Takeda’s Mobocertinib Demonstrates Robust Efficacy in EGFR Exon20 Insertion+ NSCLC with Median Overall Survival of 24 Months

May 21, 2021 /BioonBIOON/ -- Takeda Pharmaceutical (Takeda) recently announced Phase 1/2 clinical trial results of the oral targeted anti-cancer drug mobocertinib (TAK-788) for lung cancerClinical TrialLatest data from (NCT02716116). Results showed that, in adult patients with metastatic non-small cell lung cancer (mNSCLC) positive for epidermal growth factor receptor (EGFR) exon 20 insertion mutations (EGFR ex20ins+) who had previously received platinum-based chemotherapy, after more than one year (median: 14.2 months) of follow-up, mobocertinib continued to demonstrate clinically meaningful therapeutic benefits,The median overall survival (OS) was 24 months, with a 1-year survival rate of 70%.

Currently, mobocertinib is undergoing priority review by the U.S. FDA for the treatment of adult patients with metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after prior platinum-based chemotherapy and who are confirmed to be EGFR exon 20 insertion mutation-positive (EGFRex20ins+) by an FDA-approved test.FDAThe Prescription Drug User Fee Act (PDUFA) target date for this NDA has been set for October 26, 2021.

Mobocertinib is the first oral therapy specifically and selectively targeting EGFR exon 20 insertion mutations.。Currently, there are no approved targeted therapies for patients with mNSCLC harboring EGFR exon 20 insertion mutations, and current treatment regimens offer limited benefits. Mobocertinib is a small-molecule tyrosine kinase inhibitor (TKI) designed to selectively target EGFR and human epidermal growth factor receptor 2 (HER2) exon 20 insertion mutations. Notably,In the United States and China, mobocertinib has been granted Breakthrough Therapy designation for the treatment of mNSCLC with EGFR exon 20 insertion mutations.

The analysis of this phase 1/2 trial included patients with EGFR exon 20 insertion-mutated non-small cell lung cancer (EGFR ex20ins+ mNSCLC) who had previously received platinum-based chemotherapy. All patients received oral mobocertinib 160 mg once daily.

At the virtual 21st World Conference on Lung Cancer (WCLC) in 2020, hosted by the International Association for the Study of Lung Cancer (IASLC) in January this yearConferenceBased on the previously published data, the latest results show:With a median follow-up of 14.2 months, the median overall survival (OS) was 24 months.，Therapeutic responses were observed across various EGFR exon 20 insertion variants.

Other key data points were consistent with previously reported data, including a confirmed objective response rate (ORR) of 28%, a median duration of response (DoR) of 17.5 months, and a disease control rate (DCR) of 78%.

Mobocertinib Clinical Data

In this study, the observed safety profile was manageable and consistent with previous findings. Updated data showed that in patients who had previously received platinum-based chemotherapy, the most common treatment-related adverse events (TRAEs; ≥20%) were diarrhea (91%), rash (45%), paronychia (38%), decreased appetite (35%), nausea (34%), dry skin (31%), and vomiting (30%). The only Grade ≥3 TRAE (≥5%) was diarrhea (21%). Adverse events leading to treatment discontinuation (>2%) were diarrhea (4%) and nausea (4%).

Suresh S. Ramalingam, Associate Director of the Winship Cancer Institute at Emory University, stated: “The latest results from the mobocertinib phase 1/2 study show that the objective response rate, duration of response, and overall survival are highly encouraging in patients previously treated with platinum-based chemotherapy.”

TakedaTumorDr. Christopher Arendt, Director of the Treatment Center, stated: "We are pleased to add this highly promising overall survival data to the evidence demonstrating mobocertinib as an effective oral treatment option for patients with EGFR exon 20 insertion mutation-positive metastatic non-small cell lung cancer (mNSCLC) who have previously received platinum-based chemotherapy. Currently, mobocertinib is under U.S."FDApriority review, we look forward to continuing our dialogue with regulatory authorities worldwide to bring mobocertinib as a new treatment option for these patients.”

Chemical structure of mobocertinib (Image source: medchemexpress.cn)

Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 85% of lung cancer cases. Patients with EGFR exon 20 insertion mutations account for only 1–2% of NSCLC patients and have a worse prognosis compared to other EGFR mutations,There are currently no treatments available for EGFR exon 20 insertion mutations., currently available EGFR-TKIs and chemotherapy provide limited benefit to these patients.

Mobocertinib is a potent small-molecule tyrosine kinase inhibitor (TKI) specifically designed to selectively target EGFR and HER2 exon 20 insertion mutations.In 2019, the US FDA granted orphan drug designation (ODD) to mobocertinib for the treatment of lung cancer patients with HER2 or EGFR mutations (including exon 20 insertion mutations). In April 2020, the USFDAMobocertinib was granted breakthrough therapy designation for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or after platinum-based chemotherapy and harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations. In October 2020, mobocertinib was granted breakthrough therapy designation (BTD) by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) for the same indication.

Patients with EGFR exon 20 insertion mutation-positive mNSCLC face significant challenges due to the limited benefit of current treatment options, resulting in poor survival outcomes.Mobocertinib has the potential to become the first oral targeted therapy for the treatment of EGFR exon 20 insertion mutation-positive lung cancer., will provide a new effective treatment option for these patients. (Bioon.com)

Original Source: Takeda Presents Updated Results for Mobocertinib, Further Substantiating the Clinical Benefit in Patients with EGFR Exon20 Insertion+ mNSCLC