FDA Discussion Prompts Voluntary Withdrawal of BLA for I-DXd in ES-SCLC

Developers at Daiichi Sankyo and Merck have voluntarily withdrawn a biologics license application (BLA) seeking accelerated approval of ifinatamab deruxtecan (I-DXd) for adults with extensive-stage small cell lung cancer (ES-SCLC) following progression on or after platinum-containing chemotherapy, according to a press release from Merck.¹

Why was the application for I-DXd withdrawn?

Following a discussion with the FDA surrounding data supporting the BLA, including those from the phase 2 IDeate-Lung01 trial (NCT05280470), developers withdrew the application due to the findings not satisfying requirements to fulfill an accelerated approval for the indication. Investigators will continue to enroll patients on the phase 3 IDeate-Lung02 trial (NCT06203210) assessing I-DXd vs chemotherapy among those with relapsed ES-SCLC previously managed with 1 prior line of platinum-based chemotherapy.

“[ES-SCLC] is a challenging disease to treat, leaving patients in need of new options,” Abderrahmane Laadem, MD, head of therapeutic area oncology development at Daiichi Sankyo, said in the press 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.”

What is I-DXd, and what is its regulatory history?

Developers engineered I-DXd as an investigational B7-H3–directed antibody drug conjugate (ADC). It is made of a humanized anti-B7-H3 IgG1 monoclonal antibody linked to various topoisomerase I inhibitor payloads via tetrapeptide-based cleavable linkers.

The FDA previously granted priority review to I-DXd as a treatment for this SCLC population in April 2026 as part of the Real-Time Oncology Review program and Project Orbis, which are collectively intended to bring novel cancer therapies to patients as soon as possible.² Supporting data for the BLA came from the IDeate-Lung01 trial as well as the pan-tumor phase 1/2 IDeate-PanTumor01 trial (NCT04145622).

According to data from the IDeate-Lung01 published in the Journal of Clinical Oncology, the confirmed objective response rate (ORR) was 48.2% (95% CI, 39.6%-56.9%) among 137 evaluable patients who received I-DXd at 12 mg/kg across parts 1 and 2 of the study.³ Other data showed that the disease control rate (DCR) was 87.6% (95% CI, 80.9%-92.6%), the median progression-free survival (PFS) was 4.9 months (95% CI, 4.2-5.5) based on blinded independent central review (BICR), and the median overall survival (OS) was 10.3 months (95% CI, 9.1-13.3).

Regarding safety, 89.8% of the study population experienced any-grade treatment-related adverse effects (TRAEs), which included grade 3 or higher TRAEs in 36.5%. The most common any-grade TRAEs included nausea (43.1%), anemia (34.3%), and neutropenia (34.3%). Furthermore, treatment-associated interstitial lung disease (ILD) or pneumonitis based on adjudication committee evaluation occurred in 12.4% of patients.

Investigators of the international, open-label, phase 2 IDeate-Lung01 trial evaluated I-DXd among patients with ES-SCLC across 2 parts. In the dose-optimization phase of the study, patients were randomly assigned to I-DXd at 8 mg/kg or 12 mg/kg. As part of the extension phase, patients received the agent at 12 mg/kg based on results from part 1 of the trial.

The trial’s primary end point was confirmed ORR based on BICR evaluation using RECIST v1.1 criteria. Secondary end points included DCR, duration of response, time to response, and PFS.

“While we are disappointed that the current dataset [is] 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. We would like to thank the patients, their families, and investigators who have participated or continue to participate in these studies,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, concluded.¹

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 October 1, 2026. https://tinyurl.com/3wfm7fjh
2. 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. Daiichi Sankyo. April 13, 2026. Accessed October 1, 2026. https://tinyurl.com/4txu4rr9
3. 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