Phase 3 Trial of Ifinatamab Deruxtecan for Relapsed Small Cell Lung Cancer Starts

BASKING RIDGE, NJ & RAHWAY, NJ, USA I August 01, 2024 I Daiichi Sankyo (TSE: 4568) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, have announced the dosing of the first patient in the IDeate-Lung02 phase 3 clinical trial. This study aims to assess the efficacy and safety of ifinatamab deruxtecan (I-DXd) in patients with relapsed small cell lung cancer (SCLC) compared to chemotherapy treatments chosen by physicians.

Ifinatamab deruxtecan is an investigational, first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) developed by Daiichi Sankyo and co-developed with Merck. SCLC, which represents roughly 15% of all lung cancer cases, is known for its aggressive nature and rapid progression to metastatic stages. The five-year survival rate for metastatic SCLC is a mere 3%. Approximately 65% of SCLC tumors exhibit moderate-to-high expression of the B7-H3 protein, a marker associated with disease progression and poor prognosis.

Dr. Mark Rutstein, Global Head of Oncology Clinical Development at Daiichi Sankyo, emphasized the dire need for improved treatments for SCLC patients. He described the IDeate-Lung02 trial as a crucial step toward potentially introducing a new therapeutic option for this challenging cancer type. Dr. Marjorie Green, Senior Vice President and Head of Oncology Global Clinical Development at Merck Research Laboratories, echoed this sentiment, highlighting the trial's importance in their continued collaboration with Daiichi Sankyo. She noted that this trial follows the recent initiation of the REJOICE-Ovarian01 phase 2/3 study for raludotatug deruxtecan.

The IDeate-Lung02 trial is founded on promising results from a subgroup analysis of the IDeate-PanTumor01 phase 1/2 trial, presented at the 2023 World Conference on Lung Cancer. This phase 3 trial will be a multicenter, randomized, open-label study comparing ifinatamab deruxtecan to physician-selected chemotherapy options (amrubicin, lurbinectedin, or topotecan) in patients with relapsed SCLC who have undergone one prior line of platinum-based chemotherapy. Participants will be randomized to receive either ifinatamab deruxtecan (12 mg/kg) or a chemotherapy regimen chosen by their physician.

The trial's dual primary endpoints are the objective response rate (ORR) assessed by blinded independent central review (BICR) and overall survival. Secondary endpoints will include ORR as assessed by investigators, progression-free survival, duration of response, disease control rate, and time to response, evaluated by both BICR and investigators. The study aims to enroll approximately 460 patients across various regions, including Asia, Europe, Oceania, North America, and South America.

Small cell lung cancer remains a significant global health challenge, with over 2.48 million new lung cancer cases reported in 2022. Despite some benefits from current first-line therapies for advanced SCLC, second-line treatment options provide limited clinical benefits, underscoring the need for innovative approaches.

B7-H3, a transmembrane protein in the B7 family, is overexpressed in many cancer types, including SCLC. Its overexpression is linked to poor prognoses, making it a promising target for therapeutic intervention. Currently, no B7-H3 directed medicines are approved for cancer treatment.

Ifinatamab deruxtecan represents a potential breakthrough as a B7-H3 directed ADC. Developed using Daiichi Sankyo’s proprietary DXd ADC technology, it combines a humanized anti-B7-H3 IgG1 monoclonal antibody with topoisomerase I inhibitor payloads via cleavable linkers. This investigational drug is being evaluated in multiple global trials, including the phase 3 IDeate-Lung02, the phase 2 IDeate-Lung01, and the phase 1/2 IDeate-PanTumor01.

Daiichi Sankyo and Merck’s partnership, initiated in October 2023, aims to develop and commercialize several ADCs, with Daiichi Sankyo retaining exclusive rights in Japan. The DXd ADC portfolio currently includes six ADCs targeting various cancers, demonstrating Daiichi Sankyo’s commitment to advancing innovative cancer therapies.

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