Daiichi Sankyo and Merck announced that the first patient has been dosed in the IDeate-Lung02 phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) in patients with relapsed small cell lung cancer (SCLC) versus treatment of physician?s choice of chemotherapy. Ifinatamab deruxtecan is a specifically engineered potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Merck. Small cell lung cancer is the second most common type of lung cancer, accounting for about 15% of cases.

SCLC is aggressive and progresses rapidly to the metastatic stage, which has a five-year survival rate of only 3%. Approximately 65% of all SCLC tumors have a moderate-to-high expression of the protein B7-H3, which is associated with disease progression and poor prognosis. The initiation of IDeate-Lung02 is based on updated results from a subgroup analysis of the IDeate-PanTumor01 phase 1/2 trial of ifinatamab deruxtecan presented at the 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer.

IDeate-Lung02 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of ifinatamab deruxtecan (I-DXd) versus treatment of physician?s choice of chemotherapy (amrubicin, lurbinectedin or topotecan) in patients with relapsed SCLC following disease progression with only one prior line of platinum-based chemotherapy. Eligible patients will be randomized to receive ifinatamab deruxtecan (12 mg/kg) or physician?s choice of chemotherapy. The dual primary endpoints are objective response rate as assessed by blinded independent central review and overall survival.

Secondary endpoints include ORR as assessed by investigator, and progression-free survival, duration of response, disease control rate and time to response ? all assessed by both BICR and investigator. IDeate-Lung02 is expected to enroll approximately 460 patients across Asia, Europe, Oceania, North America and South America.

More than 2.48 million lung cancer cases were diagnosed globally in 2022. Small cell lung cancer is the second most common type of lung cancer, accounting for about 15% of cases.1 SCLC is aggressive and progresses rapidly to the metastatic stage, which has a five-year survival rate of only 3%. While conventional first-line therapy for patients with advanced SCLC may help some patients live longer, the current second-line standard of care offers limited clinical benefit and new treatment approaches are needed.

B7-H3 is a transmembrane protein that belongs to the B7 family of proteins which bind to the CD28 family of receptors that includes PD-1. B7-H3 is overexpressed in a wide range of cancer types, including small cell lung cancer, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. There are currently no B7-H3 directed medicines approved for the treatment of any cancer. Ifinatamab deruxtecan (I-DXd) is an investigational, potential first-in-class B7-H3 directed ADC.

Designed using Daiichi Sankyo?s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Ifinatamab deruxtecan is being evaluated in a global development program, which includes IDeate-Lung02, a phase 3 trial in patients with relapsed SCLC versus investigator?s choice of chemotherapy, IDeate-Lung01, a phase 2 monotherapy trial in patients with previously treated extensive-stage SCLC and IDeate-PanTumor01, a phase 1/2 first-in-human trial in collaboration with Sarah Cannon Research Institute (SCRI) with study operational oversight and delivery provided through SCRI?s early phase oncology clinical research organization, SCRI Development Innovations in Nashville, TN. Ifinatamab deruxtecan was granted orphan drug designation by the U.S. Food and Drug Administration in April 2023 and by the European Commission in February 2024 for the treatment of SCLC.

Daiichi Sankyo and Merck (known as MSD outside of the United States and Canada) entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply.