FDA Application Withdrawn for I-DXd in Small Cell Lung Cancer

Daiichi Sankyo and Merck have voluntarily withdrawn their biologics license application (BLA) for the B7-H3–directed antibody-drug conjugate ifinatamab deruxtecan (I-DXd) in previously treated extensive-stage small cell lung cancer (ES-SCLC), after the FDA communicated that data from the phase 2 IDeate-Lung01 trial (NCT05280470) and other evidence did not meet accelerated approval requirements.¹

The BLA, which covered adults with disease progression on or after platinum-based chemotherapy, had received Priority Review in April 2026, following breakthrough therapy designation in August 2025, and carried an October 10, 2026, target action date.^2,3 Enrollment continues in the phase 3 IDeate-Lung02 trial of I-DXd vs physician's choice of amrubicin, lurbinectedin, or topotecan in relapsed ES-SCLC after 1 prior platinum-based regimen.¹

The primary analysis of IDeate-Lung01, presented at the 2025 World Conference on Lung Cancer and published in the Journal of Clinical Oncology, included 137 patients treated with I-DXd at 12 mg/kg. The confirmed objective response rate (ORR) by blinded independent central review (BICR) was 48.2% (95% CI, 39.6%-56.9%), with 3 complete responses, 63 partial responses, and 54 cases of stable disease. The disease control rate (DCR) was 87.6% (95% CI, 80.9%-92.6%). Responses occurred at a median of 1.4 months (range, 1.0-8.1), and the median duration of response (DOR) was 5.3 months (95% CI, 4.0-6.5). At a median follow-up of 12.8 months, median progression-free survival (PFS) was 4.9 months (95% CI, 4.2-5.5) and median overall survival (OS) was 10.3 months (95% CI, 9.1-13.3).^2,4,5

Second-line patients (n = 32) fared numerically better: an ORR of 56.3% (95% CI, 37.7%-73.6%), a DCR of 96.9% (95% CI, 83.8%-99.9%), a median DOR of 7.2 months (95% CI, 3.6-not evaluable), median PFS of 5.6 months (95% CI, 3.9-8.1), and median OS of 12.0 months (95% CI, 7.3-19.1). In the third-line or later subgroup (n = 105), the ORR was 45.7% (95% CI, 36.0%-55.7%), including 3 complete and 45 partial responses, with a DCR of 84.8% (95% CI, 76.4%-91.0%) and a median DOR of 4.3 months (95% CI, 3.7-5.8). Among 65 patients with baseline brain metastases, the exploratory intracranial ORR was 46.2% (95% CI, 33.7%-59.0%).²

“Extensive-stage small cell lung cancer is a challenging disease to treat, leaving patients in need of new options,” Abderrahmane Laadem, MD, head, therapeutic area oncology development, Daiichi Sankyo, stated in a news release.¹ “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.”

IDeate-Lung01 Safety Findings

Treatment-related adverse events (TRAEs) of any grade occurred in 89.8% of patients, including grade 3 or higher events in 36.5% and grade 5 events in 4.4%. The most common grade 3 or higher TRAEs were neutropenia (13.9%), lymphopenia (12.4%), and anemia (10.2%). An independent committee adjudicated treatment-related interstitial lung disease (ILD)/pneumonitis in 17 patients (12.4%): 11 grade 1 or 2 (8.0%), 4 grade 3 (2.9%), and 2 grade 5 (1.5%). Median treatment duration was 4.8 months (range, 0.7-22.7) at the March 3, 2025, data cutoff.^2,5

IDeate-Lung01 Trial Design

IDeate-Lung01 is a global, multicenter, randomized, open-label, 2-part phase 2 study that enrolled 187 patients in Asia, Europe, and North America. Eligible patients had ES-SCLC treated with 1 or more platinum-based regimens and up to 3 prior lines. Asymptomatic brain metastases, treated or untreated, were allowed; a history of ILD/pneumonitis requiring steroids, current ILD/pneumonitis at screening, or clinically severe pulmonary compromise from intercurrent illness was exclusionary.¹

In the dose-optimization part, patients were randomly assigned 1:1 to I-DXd at 8 or 12 mg/kg intravenously every 3 weeks; the dose-expansion part used 12 mg/kg on the same schedule. The primary end point was ORR by BICR per RECIST v1.1, and secondary end points included DOR, PFS, DCR, time to response, OS, pharmacokinetics, and safety.¹

In the 12-mg/kg cohort, 23.4%, 54.7%, and 21.9% had received 1, 2, and 3 prior lines, respectively. Previous therapies included immunotherapy (81%), topoisomerase I inhibitors (32.1%), lurbinectedin (21.2%), amrubicin (8.8%), and DLL3-targeted T-cell engagers (8.0%).^2,5

“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 and other types of difficult-to-treat cancer,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, stated in the news release.¹ “We would like to thank the patients, their families and investigators who have participated or continue to participate in these studies.”

REFERENCES

1. Ifinatamab deruxtecan Biologics License Application for certain patients with previously treated extensive-stage small cell lung cancer voluntarily withdrawn. News release. Merck. September 25, 2026. Accessed September 28, 2026. https://tinyurl.com/mr9y4hus

2. Ifinatamab deruxtecan demonstrated clinically meaningful response rates in patients with extensive-stage small cell lung cancer in IDeate-Lung01 phase 2 trial. News release. Merck. September 7, 2025. Accessed September 28, 2026. https://tinyurl.com/yc3umfse

3. Ifinatamab deruxtecan granted priority review in the U.S. for adult patients with previously treated extensive-stage small cell lung cancer who experienced disease progression on or after platinum-based chemotherapy. News release. Merck. April 13, 2026. Accessed September 28, 2026. https://tinyurl.com/3c2b6kpd

4. Rudin CM, Johnson ML, Paz-Ares L, et al. Ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer: primary analysis of the phase II IDeate-Lung01 trial. J Clin Oncol. 2026;44(4):261-273. doi:10.1200/JCO-25-02142.

5. Ifinatamab deruxtecan demonstrates high response rate in previously treated extensive-stage small cell lung cancer: phase 2 IDeate-Lung01 trial. News release. International Association for the Study of Lung Cancer. September 7, 2025. Accessed September 28, 2026. https://tinyurl.com/2thxatmc