This is a multicenter, randomized, open-label, parallel-controlled phase 3 study. This study aims to evaluate the efficacy and safety of JMT101 combined with Osimertinib compared with Cisplatin combined with pemetrexed in participants with local advanced or metastatic non-small-cell lung cancer harboured EGFR 20ins mutation without prior systemic therapy.

Primary objective of this study is to assess the efficacy of JMT101 combined with Osimertinib versus Cisplatin combined with pemetrexed using by （Independent Review Center）IRC-assessed Progression Free Survival (PFS) per RECIST 1.1 as primary endpoint. Approximately 398 participants are estimated to be randomized into the study. Participants enrolled will be randomized to JMT101 or Cisplatin chemotherapy in a 1:1 manner, stratified by baseline brain metastasis (with/without) and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (0 versus 1).

Inclusion Criteria:

1. Age between 18-75 years old.
2. Histologically or cytologically confirmed diagnosis of NSCLC, locally advanced (Stage IIIB and IIIC according to the 8th edition of the IASLC TNM staging criteria) or metastatic (Stage IV), not suitable for curative therapy. For central laboratory confirmation of EGFR exon 20 insertion mutation with tumour tissue/blood sample.
3. At least 1 measurable lesion per RECIST Version 1.1
4. Life expectancy ≥ 12 weeks
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
6. Adequate organ and hematologic function

Exclusion Criteria:

1. Prior treatment with any systemic anti-cancer therapy for locally advanced or metastatic NSCLC.
2. Central nervous system metastasis with associated symptom and signs.
3. Concurrent EGFR mutations: exon 19 deletion, L858R, T790M, G719X, S768I, or L861Q.
4. History of interstitial lung disease, or infectious pneumonitis need heavy antibiotics therapy
5. As judged by the investigator, unsuitable for attending the study.