Daiichi Sankyo and Merck Withdraw FDA Accelerated Approval BLA for Ifinatamab Deruxtecan in Extensive-Stage SCLC
核心洞察
Daiichi Sankyo and Merck (搜索) voluntarily withdrew the U.S. BLA seeking accelerated approval of ifinatamab deruxtecan for extensive-stage small cell lung cancer (搜索) after platinum-based chemotherapy.
The companies said FDA discussions concluded that data including the IDeate-Lung01 phase 2 trial did not satisfy requirements for accelerated approval in the proposed indication.
Enrollment continues in the phase 3 IDeate-Lung02 trial comparing ifinatamab deruxtecan with physician's choice chemotherapy, with enrollment described as near completion.
Daiichi Sankyo and Merck (搜索) have voluntarily withdrawn the Biologics License Application (BLA) seeking accelerated approval in the United States for ifinatamab deruxtecan (I-DXd) in adult patients with extensive-stage small cell lung cancer (搜索) (ES-SCLC) whose disease progressed on or after platinum-based chemotherapy. The decision followed discussions with the U.S. Food and Drug Administration (搜索), which concluded that the data supporting the application, including results from the phase 2 IDeate-Lung01 trial, do not satisfy the requirements needed to support an accelerated approval for the proposed indication.
The accelerated approval pathway allows earlier approval of medicines based on surrogate endpoints for serious conditions with an unmet medical need. In this case, the submitted dataset was judged insufficient for that route.
Phase 3 Program Continues
Patient enrollment continues in the phase 3 IDeate-Lung02 trial, which is evaluating the efficacy and safety of ifinatamab deruxtecan versus treatment of physician's choice of chemotherapy, including amrubicin, lurbinectedin or topotecan, in patients with relapsed ES-SCLC following disease progression with only one prior line of platinum-based chemotherapy.
"Extensive-stage small cell lung cancer (搜索) is a challenging disease to treat, leaving patients in need of new options," said Abderrahmane Laadem, MD, head of therapeutic area oncology development at Daiichi Sankyo. "Enrollment into the IDeate-Lung02 phase 3 trial is near completion and we look forward to assessing the potential for a future filing of ifinatamab deruxtecan with the FDA and other global regulatory authorities based on those results."
Marjorie Green, MD, senior vice president and head of oncology, global clinical development at Merck (搜索) Research Laboratories, said the companies remain committed to the program despite the withdrawal. "While we are disappointed that the current dataset are not supportive of an approval at this time, we are continuing to evaluate the role of ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer (搜索) and other types of difficult-to-treat cancer," she said.
IDeate-Lung01 Design and Endpoints
IDeate-Lung01 (NCT05280470) was a global, multicenter, randomized, open-label, two-part phase 2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with ES-SCLC previously treated with at least one prior line of platinum-based chemotherapy and a maximum of three prior lines of therapy. The trial enrolled 187 patients across Asia, Europe and North America.
Patients with asymptomatic brain metastases, whether untreated or previously treated, were eligible. Patients with a history of interstitial lung disease (ILD) or pneumonitis requiring steroid treatment, or current ILD/pneumonitis at screening, and those with clinically severe pulmonary compromise from intercurrent pulmonary illnesses, were excluded.
In the dose optimization part of the trial, patients were randomized 1:1 to receive ifinatamab deruxtecan at 8 or 12 mg/kg intravenously once every three weeks. In the dose expansion part, patients received 12 mg/kg intravenously at the same interval. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review (BICR) per RECIST v1.1. Secondary endpoints included duration of response, progression-free survival, disease control rate, time to response, overall survival, pharmacokinetics and safety. Intracranial ORR was assessed by BICR as an exploratory analysis.
Broader Development Across Three Phase 3 Trials
Beyond IDeate-Lung02, two additional phase 3 trials of ifinatamab deruxtecan are underway in advanced or metastatic disease: IDeate-Prostate01 in castration-resistant prostate cancer (搜索) (CRPC) and IDeate-Esophageal01 in esophageal squamous cell carcinoma (搜索) (ESCC). The global development program is evaluating the agent as monotherapy and in combination with other cancer medicines across multiple tumor types.
Ifinatamab deruxtecan is an investigational, potential first-in-class B7-H3 (搜索) directed antibody drug conjugate (ADC). It is built on Daiichi Sankyo's DXd ADC technology and consists of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to topoisomerase I inhibitor payloads, an exatecan derivative known as DXd, via tetrapeptide-based cleavable linkers. The agent has received orphan drug designation for SCLC from the FDA, the European Commission, Japan's Ministry of Health, Labour and Welfare, South Korea's Ministry of Food and Drug Safety and Taiwan's Food and Drug Administration. It also holds FDA orphan drug designation for esophageal cancer.
B7-H3 (搜索) is a transmembrane protein in the B7 family, whose members bind CD28 family receptors including PD-1. It is overexpressed in a range of cancer types including SCLC, CRPC and ESCC, and its overexpression has been correlated with poor prognosis. No B7-H3 directed medicines are currently approved for the treatment of cancer.
Disease Burden and Collaboration Terms
Approximately 250,000 patients are diagnosed with small cell lung cancer (搜索) globally each year. In the U.S., there were approximately 27,000 new cases in 2025, accounting for about 12% of all lung cancer cases. SCLC is aggressive and progresses rapidly to the distant metastatic stage, which carries a low five-year survival rate. While conventional standard of care treatments for advanced SCLC may improve outcomes, additional subsequent treatment approaches are needed.
Daiichi Sankyo and Merck (搜索) entered a global collaboration in October 2023 to jointly develop and commercialize ifinatamab deruxtecan, raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), with Daiichi Sankyo retaining exclusive rights in Japan and sole responsibility for manufacturing and supply. In August 2024, the agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide except in Japan, where Merck holds exclusive rights and sole manufacturing and supply responsibility.
Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610, DS3790 and DS1025 are investigational medicines that have not been approved for any indication in any country, and their safety and efficacy have not been established.