Study of Izalontamab Brengitecan versus Platinum- Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer after failure of EGFR TKI Therapy

INTERVENTION: Intervention1: Izalontamab brengitecan (iza‐bren): 2.0 or 2.5 mg/kg IV Day 1 and 8 every 3 weeks (Phase 2) Intervention2: Iza‐bren (RP3D IV): Dose selected from Phase 2, Day 1 and 8 every 3 weeks (Phase 3) Control Intervention1: Platinum Based Chemotherapy (Carboplatin or Cisplatin + Pemetrexed): Investigator s choice, per described regimens (Phase 2) Control Intervention2: Platinum Based Chemotherapy (Carboplatin or Cisplatin + Pemetrexed): Investigator s choice, per described regimens (Phase 3) CONDITION: Health Condition 1: C349‐ Malignant neoplasm of unspecifiedpart of bronchus or lung PRIMARY OUTCOME: ‐ To compare the PFS of iza‐bren at RP3D vs ; PBC in participants with advanced EGFRmt ; NSCLC cancer and disease progression after any ; 3rd generation TKIs ; ; ‐ To determine the RP3D for iza‐bren to advance ; to Stage 2 (Phase 3) of the study ; Timepoint: ‐ PFS by RECIST v1.1 per BICR ; ; ‐RP3D determined based on the totality of safety, ; tolerability, efficacy, and PK/pharmacodynamic ; data ; SECONDARY OUTCOME: ‐ To estimate the efficacy of 2 different dose ; levels of iza‐bren (2.0 mg/kg [Arm A] and 2.5 ; mg/kg [Arm B] D1D8Q3W) vs PBC ; Timepoint: ‐OR by RECIST v1.1 per BICR ; ‐PFS rates by RECIST v1.1 per BICR ; ; efficacy/activity of iza‐bren at RP3D vs PBCTimepoint: ; ‐ PFS by RECIST v1.1 per investigator assessment ; ‐OR by RECIST v1.1 per BICR ; ‐DCR by RECIST v1.1 per BICR ; ‐DOR by RECIST v1.1 per BICR ; ‐TTR by RECIST v1.1 per BICR To compare the OS of iza‐bren at RP3D vs PBC ; in participants with advanced EGFRmt NSCLC ; cancer and disease progression after any 3rd ; generation TKIs ; Timepoint: OS INCLUSION CRITERIA: ‐Participants or their legally acceptable representative must have signed and dated an IRB or IEC approved written ICF in accordance with regulatory local and institutional guidelines. This ICF must be obtained before performing any protocol related procedures that are not part of normal patient care Note Participants must agree to comply with the requirements and restrictions listed in the IC and in this protocol ‐ Eastern Cooperative Oncology Group ECOG Performance Status of 0 to 1 ‐Histologically or cytologically confirmed diagnosis of non squamous NSCLC not amenable to treatment in curative intent. ‐Evidence of documented EGFR TKI sensitizing deletion mutation according to local test in EGFR exon 19 ex19del or leucin arginine substitution point mutation in EGFR exon 21ex21L858R at or after the time of disease diagnosis and prior to initiation of an EGFR TKI. Note EGFR mutational status can be based on e