Takeda‘s Exkivity (mobocertinib) is the first and only targeted therapy to be approved for locally advanced or metastatic epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins)-positive non-small cell lung cancer (NSCLC) in China. The drug is approved under the National Medical Products Administration’s Breakthrough Therapy program for second-line treatment. However, there still exists room for improvement to treat this subset of patients, given the treatment outcomes and safety of the molecule in the pivotal Phase II trial, says GlobalData, a leading data and analytics company.

According to GlobalData’s Pharmaceutical Intelligence Center, the total number of incident cases of EGFRex20ins-positive NSCLC in urban China are expected to increase from 7,637 to 10,265, at an annual growth rate of 4.3% during 2021 to 2029.

Neha Myneni, Pharma Analyst at GlobalData, comments: “High success rates of targeted therapies in cancer have led to the improvement in overall survival while decreasing undesirable adverse effects. However, certain oncogene mutations have turned out to be difficult to treat, leaving the patients with limited to no treatment options and high unmet need. Though many targeted therapies are currently available for EGFR-positive NSCLC, EGFR exon20ins have frequently demonstrated resistance to classical EGFR inhibition.”

Targeted treatments are expected to delay disease progression as the majority of patients receiving platinum-based chemotherapy as standard first-line treatment for EGFRex20ins-positive NSCLC develop progressive disease within six months.

Exkivity’s approval is based on data from the global Phase 1/2 clinical trial (NCT02716116) (n=114) that demonstrated its clinical benefit and durable responses in EGFR exon20ins NSCLC. The overall response rate was around 28% in this pivotal study, which is far less than the previously confirmed ORR of 43% in a 28-patient dataset of the same trial. Moreover, about 40% of patients experienced ≥grade 3 treatment-related adverse events, and 21% of patients experienced ≥grade 3 diarrhoea, which required dose reduction or even discontinuation, indicating room for further improvement.

Contrary to the treatment outcomes and safety data reported in Exkivity’s pivotal trial, the supporting data used for regulatory submission for some of these competitor molecules is strong.

The initial results from the Phase I CHRYSALIS study (n=195) for amivantamab show an ORR of 40% and ≥grade 3 treatment-related adverse events were reported in <10% of patients. Pooled data from the WU-KONG1 and WU-KONG2 studies (n=102) for sunvozertinib shows the highest ORR of 41.1% and confirmed ORR of 37.5% across all dose levels. Furthermore, ≥grade 3 treatment-related adverse events were observed in 39.2% of patients, and ≥grade 3 diarrhoea was observed in 4.9% of patients.

Myneni concludes: “Considering the high prevalence of NSCLC in China, domestic companies are also involved in developing novel targeted therapies for the treatment of this disease. This could potentially increase the competition for Takeda’s Exkivity if sunvozertinib is approved in the near future. Also, drugs developed by domestic companies will have a cost benefit over foreign players. Hence, strong supporting data for Exkivity in a confirmatory trial is required to provide stronger evidence of its clinical benefit over the potential competitors.”