Daiichi Sankyo and Merck withdrew the I-DXd BLA in ES-SCLC after FDA discussions found phase 2 IDeate-Lung01 data insufficient for accelerated approval.
The biologics license application (BLA) seeking accelerated approval of ifinatamab deruxtecan (I-DXd) for adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed on or following platinum-based chemotherapy has been voluntarily withdrawn, according to a news release from Merck.¹
Merck and Daiichi Sankyo, which are codeveloping the agent, repoted that the decision followed discussions with the FDA indicating that the supporting data, including findings from the phase 2 IDeate-Lung01 trial (NCT05280470), do not meet the requirements for accelerated approval in the proposed indication. The regulatory agency had accepted the BLA and granted it priority review in April 2026.²
In the primary analysis of IDeate-Lung01, published in the Journal of Clinical Oncology, patients treated with I-DXd at 12 mg/kg (n = 137) achieved a confirmed objective response rate (ORR) of 48.2% (95% CI, 39.6%-56.9%) per blinded independent central review (BICR).³ The median duration of response (DOR) was 5.3 months (95% CI, 4.0-6.5), the median progression-free survival (PFS) was 4.9 months (95% CI, 4.2-5.5), and the estimated 9-month overall survival (OS) rate was 59.1% (95% CI, 50.4%-66.8%).
In the news release, Marjorie Green, MD, senior vice president and head of oncology, global clinical development, at Merck Research Laboratories, said the companies were “disappointed that the current dataset are not supportive of an approval at this time,” adding that examination of I-DXd in ES-SCLC and other difficult-to-treat cancers is ongoing.¹
Enrollment continues in the randomized, open-label, phase 3 IDeate-Lung02 trial (NCT06203210), which is comparing I-DXd with physician’s choice of topotecan (Hycamtin), amrubicin, or lurbinectedin (Zepzelca) in patients with relapsed SCLC.¹,⁴ According to Abderrahmane Laadem, MD, head of therapeutic area oncology development at Daiichi Sankyo, enrollment is nearing completion, and the companies plan to examine a potential future filing with the FDA and other regulators based on those results.¹
IDeate-Lung02 is enrolling adults with ES-SCLC who received only one prior platinum-based line of at least 2 cycles, with a chemotherapy-free interval of at least 30 days, and an ECOG performance status of 0 or 1.⁴ Patients with brain metastases or leptomeningeal disease may enroll if protocol criteria are met; those with any history of interstitial lung disease (ILD)/pneumonitis, apart from radiation pneumonitis not requiring steroids, are excluded, as are those previously exposed to B7-H3–directed agents or topoisomerase I inhibitors. OS is the primary end point. Secondary end points include ORR, PFS, DOR, disease control, and time to response (TTR) by BICR and investigator assessment, as well as patient-reported outcomes, safety, and pharmacokinetics. Target enrollment is 540 patients, with primary completion anticipated in January 2028.
Two additional phase 3 trials are underway: IDeate-Prostate01 (NCT06925737) in castration-resistant prostate cancer and IDeate-Esophageal01 (NCT06644781) in esophageal squamous cell carcinoma.¹
I-DXd is a B7-H3–directed antibody-drug conjugate composed of a humanized anti–B7-H3 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload (DXd, an exatecan derivative) via tetrapeptide-based cleavable linkers.¹ No B7-H3–directed therapy is approved for cancer. The agent holds orphan drug designation for SCLC from the FDA, the European Commission, Japan’s Ministry of Health, Labour and Welfare, and the Taiwan Food and Drug Administration.
The global, multicenter, randomized, open-label, 2-part IDeate-Lung01 trial enrolled 187 patients in Asia, Europe, and North America with ES-SCLC who had received at least one prior line of platinum-based chemotherapy and no more than three prior lines of therapy.¹ Patients with asymptomatic brain metastases were eligible; those with ILD/pneumonitis requiring steroids were not. In part 1, patients were randomly assigned 1:1 to I-DXd at 8 or 12 mg/kg intravenously every 3 weeks; in part 2, all patients received 12 mg/kg. The primary end point was ORR by BICR per RECIST 1.1.
In part 1, the ORR was 26.1% (95% CI, 14.3%-41.1%) at 8 mg/kg (n = 46) and 54.8% (95% CI, 38.7%-70.2%) at 12 mg/kg (n = 42).³ Across the 12-mg/kg population, the median TTR was 1.4 months (range, 1.0-8.1). In an exploratory analysis presented at the 2025 ESMO Congress, patients with baseline brain metastases (n = 65) had an intracranial confirmed ORR of 46.2% (95% CI, 33.7%-59.0%).⁵
Among patients who received I-DXd at 12 mg/kg (n = 137), any-grade treatment-emergent adverse effects (TEAEs) occurred in 98.5%, grade 3 TEAEs in 62.0%, and serious TEAEs in 39.4%.³ TEAEs led to dose delay in 35.8% of patients, dose reduction in 17.5%, dose interruption in 1.5%, and treatment discontinuation in 10.9%; TEAEs associated with death were reported in 11.7%.
The most common any-grade TEAEs were nausea (48.2%), anemia (45.3%), decreased appetite (38.7%), and neutropenia (38.0%).³
Disclosures: IDeate-Lung01 and IDeate-Lung02 are sponsored by Daiichi Sankyo, with Merck as collaborator under a global codevelopment agreement.
