Mobocertinib Garners Approval in China for EGFR Exon 20 Insertion+ NSCLC

The National Medical Products Administration (NMPA) of China has approved mobocertinib (Exkivity) for the treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations and whose disease progressed on or following platinum-based chemotherapy.¹

The agent was reviewed as part of the NMPA’s breakthrough therapy program, and as such, full approval of the oral TKI may depend upon verification of clinical benefit in a confirmatory trial. With this decision, however, mobocertinib is the first and only treatment available for this population in China.

“The approval of [mobocertinib] in China for patients with locally advanced or metastatic EGFR exon 20 insertion–positive NSCLC was only possible through dedicated collaboration and support from the NMPA and the Chinese government,” Awny Farajallah, head of Global Medical Affairs Oncology at Takeda, stated in a press release. “Lung cancer is a devastating disease, and we know the discovery and delivery of precision medicine like [mobocertinib] to target cancer types that are hard to treat have the potential to improve patient outcomes.”

The approval was supported by findings from a subset of platinum-pretreated patients (n = 114) enrolled to an international, open-label, multicohort phase 1/2 trial (NCT02716116) of the drug, which enrolled patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC and a documented EGFR exon 20 insertion mutation.

Participants were administered mobocertinib at a once-daily dose of 160 mg. Treatment was continued until disease progression or unacceptable toxicity. Objective response rate (ORR) by RECIST v1.1 criteria as evaluated by blinded independent central review (BICR) served as the major efficacy outcome measure for the trial. Another key efficacy outcome measure was duration of response (DOR) by BICR.

Data from this subset showed that mobocertinib elicited an independent review committee (IRC)–assessed confirmed ORR of 28% (95% CI, 20%-37%) in this patient population. Moreover, the median DOR with the agent was 15.8 months. The median progression-free survival and overall survival with the TKI was 7.3 months and 20.2 months, respectively.

The investigator-assessed ORR reported with the agent was 35% (95% CI, 26%-45%), with a median DOR of 11.2 months.² Notably, 63% of responders experienced responses that lasted for more than 6 months.

Regarding safety, the treatment-related toxicities that were most frequently experienced with mobocertinib included diarrhea (92%), rash (46%), paronychia (38%), and decreased appetite (37%).

In September 2021, the FDA granted an accelerated approval to mobocertinib for use in the same patient population based on findings from the phase 1/2 trial.³

Real-world data from a multicenter, open-label clinical trial shared at the 2021 ESMO Congress showed that mobocertinib demonstrated clinically meaningful activity in this patient population.⁴ Notably, the weighted response rate was nearly 3 times higher with the TKI than with standard of care. The weighted confirmed ORRs for those treated with the agent on study vs the real-world group were 35.1% (95% CI, 26.4%-44.6%) and 11.9% (95% CI, 5.8%-18.0%), respectively (absolute difference, 23.2%; odds ratio, 3.75; 95% CI, 2.05-6.89; P < .01).

Moreover, PFS and OS were prolonged with mobocertinib vs other options typically used in the real-world setting. The weighted median PFS in the mobocertinib and the real-world groups was 7.3 months (95% CI, 5.6-8.8) and 3.3 months (95% CI, 2.2-7.3), respectively (HR, 0.57); the weighted median OS was 24.0 months (95% CI, 14.6-28.8) and 12.4 months (95% CI, 7.1-16.6), respectively (HR, 0.53).

More recently, findings from the phase 1/2 trial presented at the 2022 ASCO Annual Meeting showed that mobocertinib may have limited intracranial activity in patients with NSCLC harboring EGFR exon 20 insertion mutations and brain metastases at baseline, as a numerically lower response rate was observed with the drug in this subset.⁵

Specifically, in previously treated patients without brain metastases at baseline, the confirmed ORR with mobocertinib was 34% vs 18% in those without those metastases. The PFS in these groups was 9.2 months and 3.7 months, respectively. However, those who did not have brain metastases at baseline but whose disease progressed to the brain following initial treatment with the TKI derived a benefit from remaining on study treatment.

“We are thrilled to introduce [mobocertinib] in China as the second lung cancer therapy from Takeda and remain committed to research and development to meet the needs of this patient community,” Farajallah added in the press release.

References

1. Takeda’s Exkivity (mobocertinib) receives approval from the NMPA of China, becoming the first and only therapy available for patients with EGFR exon20 insertion+ NSCLC. News release. Takeda. January 11, 2023. Accessed January 11, 2023. https://bit.ly/3W4eyid
2. Exkivity (mobocertinib). Prescribing information; Takeda; September 2021. Accessed January 11, 2023. https://bit.ly/3vSdO58
3. Takeda's Exkivity (mobocertinib) approved by US FDA as the first oral therapy specifically designed for patients with EGFR exon20 insertion+ NSCLC. News release. Takeda. September 15, 2021. Accessed January 11, 2023. https://bit.ly/2Xm3WSY
4. Ou S-HI, Lin HM, Hong J-L, et al. 1211P Indirect comparison of mobocertinib and standard of care in platinum-pretreated patients with NSCLC with EGFR exon 20 insertion. Ann Oncol. 2021;32 (suppl 5):S964-S965. doi:10.1016/j.annonc.2021.08.1816
5. Jaane P, Ramalingam S, Yang J, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic non–small cell lung cancer (mNSCLC): treatment (tx) beyond progressive disease (PD) in platinum-pretreated patients (pts) with and without intracranial PD. J Clin Oncol. 2022; 40 (suppl 16):9099. doi:10.1200/JCO.2022.40.16_suppl.9099