IDeate-Lung02: a Phase 3 study of second-line ifinatamab deruxtecan in patients with relapsed small cell lung cancer

Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. B7 homolog 3 (B7-H3) is minimally expressed in normal tissues but highly expressed in SCLC. Ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate, has demonstrated promising efficacy and a manageable safety profile in various tumours, including SCLC. IDeate-Lung02 is a global, randomized, open-label Phase 3 study of ~540 patients with relapsed SCLC. Adults with one prior line of platinum-based systemic therapy, ECOG performance status 0-1, and ≥1 measurable lesion (per RECIST 1.1) are eligible for study participation. Patients with asymptomatic untreated or previously treated brain metastases may participate. Patients are randomized 1:1 to receive I-DXd 12 mg/kg intravenously every 3 weeks or treatment of physician's choice (topotecan, amrubicin, or lurbinectedin). Dual primary endpoints are objective response rate (ORR) by blinded independent central review (BICR) and overall survival. Secondary endpoints include ORR by investigator; progression-free survival, duration of response, disease control rate, and time to response, all by BICR and investigator; patient-reported outcomes; and safety. IDeate-Lung02 will ascertain whether I-DXd treatment after only one prior line of systemic treatment improves outcomes for patients with relapsed SCLC compared with topotecan, amrubicin, or lurbinectedin.<b>Clinical Trial Registration:</b> NCT06203210.