IDeate-Lung02

A Phase 3, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody-Drug Conjugate (ADC), Versus Treatment of Physician’s Choice (TPC) in Subjects with Relapsed Small Cell Lung Cancer (SCLC)

– Has histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC).
– Has received prior therapy with only one prior platinum-based line as systemic therapy for SCLC with at least 2 cycles of therapy and a chemotherapy free- interval of ≥30 days. Subjects with or without prior immune-checkpoint inhibitor therapy are eligible. Subjects treated with a platinum based line of therapy for prior limited-stage-small cell lung cancer (LS-SCLC) may be eligible for the study if the disease has progressed on treatment or within 6 months from platinum therapy completion: the platinum-based line of therapy will count as 1L of therapy. If the investigator believes a subject may benefit from platinum rechallenge, such subject may not participate in the study. Subjects must not have received more than one prior line of systemic therapy. One line of therapy will be defined as 1 or more drugs received prior to newly documented disease progressions. Any switch between carboplatin and cisplatin for toxicity reasons will be regarded as one line overall.
– Has documentation of radiological disease progression on or after the most recent systemic therapy.
– Has ECOG PS of ≤1 within 7 days before C1D1.
– Has no evidence of brain or leptomeningeal disease (spinal cord or central nervous system [CNS] metastases) based on history and physical examination. For subjects with evidence of brain or leptomeningeal disease, they may be eligible if condition has been treated and a lack of
progression within 4 weeks prior to initiation of study drug has been radiologically documented.
Subjects must require no treatment with steroids or anticonvulsants and have a stable neurologic status for at least 2 weeks prior to the first dose of study drug. Subjects with untreated brain metastases will be allowed if they are asymptomatic, the investigator determines there is no immediate CNS-specific treatment required, there is no significant surrounding edema, and the brain metastases are of 5 mm or less in size and 3 or fewer. Note: A baseline magnetic resonance imaging scan or computed tomography of the brain is required for all subjects at baseline.
– Has adequate organ and bone marrow function within 7 days before the start of study treatment.

– Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
– Has uncontrolled or significant cardiovascular disease
– Has clinically significant corneal disease.
– Has history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
– Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of randomization, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc) and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren’s syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen.
– On chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for lowdose inhaled steroids (for asthma/COPD), topical steroids (for mild skin conditions), or intra-articular steroid injections.
– Has history of malignancy other than SCLC within the 3 years prior to randomization, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal tract tumors, and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
– Has active, known, or suspected autoimmune disease. The following examples may be enrolled as an exception:
a. Type I diabetes mellitus/hypothyroidism only requiring hormone replacement
b. Skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment
c. Conditions not expected to recur in the absence of an external trigger