Daiichi Sankyo, Merck Pull Ifinatamab Deruxtecan BLA in SCLC

Daiichi Sankyo and Merck have voluntarily withdrawn the biologics license application (BLA) seeking accelerated approval of ifinatamab deruxtecan (I-DXd) for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed on or after platinum-based chemotherapy, the companies announced September 25, 2026.¹ The companies said the decision follows discussions with FDA indicating that data supporting the application, including from the phase 2 IDeate-Lung01 trial, do not satisfy the requirements needed for accelerated approval of the proposed indication.¹

"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," said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in a company press release.¹ "We would like to thank the patients, their families, and investigators who have participated or continue to participate in these studies."

Why was the application withdrawn?

The withdrawal followed discussions with FDA that concluded the IDeate-Lung01 dataset does not meet the bar required to support accelerated approval for the proposed indication.¹ IDeate-Lung01 (NCT05280470) is a phase 2, global, multicenter, randomized, open-label, 2-part trial that enrolled 187 patients across Asia, Europe, and North America who had received at least 1 prior line of platinum-based chemotherapy and up to 3 prior lines of therapy overall.¹^,² In the trial's dose-optimization part, patients were randomized 1:1 to ifinatamab deruxtecan at 8 mg/kg or 12 mg/kg intravenously once every 3 weeks. In the dose-expansion part, all patients received 12 mg/kg on the same schedule. The primary endpoint was objective response rate assessed by blinded independent central review.¹^,³

What's next for ifinatamab deruxtecan in this cancer?

Enrollment continues in the phase 3 IDeate-Lung02 trial, which is comparing ifinatamab deruxtecan with a physician's choice of chemotherapy, whether amrubicin, lurbinectedin, or topotecan, in patients with relapsed disease following progression after only 1 prior line of platinum-based chemotherapy.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," said Abderrahmane Laadem, MD, head, therapeutic area oncology development, Daiichi Sankyo, in the release.¹

What is ifinatamab deruxtecan?

Ifinatamab deruxtecan is an investigational, potential first-in-class antibody-drug conjugate (ADC) directed against B7-H3, a protein highly expressed across cancer types including small cell lung cancer, with overexpression linked to poor prognosis.¹ Built on Daiichi Sankyo's DXd technology, the ADC pairs a humanized anti-B7-H3 antibody with a topoisomerase I inhibitor payload.¹

FDA, European Commission, Japan's health ministry, and Taiwan's FDA have granted the ADC orphan designation for small cell lung cancer, and FDA separately granted orphan designation for esophageal cancer.¹ Daiichi Sankyo and Merck are jointly developing ifinatamab deruxtecan under a collaboration formed in October 2023 that also covers 2 other ADCs, expanded in August 2024 to include the bispecific antibody gocatamig.¹ Beyond small cell lung cancer, the companies are running phase 3 trials of the drug in castration-resistant prostate cancer and esophageal squamous cell carcinoma.¹

What are the limitations?

The withdrawal applies only to the accelerated-approval pathway for previously treated extensive-stage small cell lung cancer. It does not affect the ongoing IDeate-Lung02 trial or the drug's development in other cancers. Neither company specified which endpoints or efficacy thresholds FDA found insufficient. IDeate-Lung01's dose-expansion portion was single-arm and open-label, without a randomized comparator. No B7-H3-directed therapy is currently approved for any cancer indication, according to the companies.¹

References

1. Merck. Ifinatamab deruxtecan Biologics License Application for certain patients with previously treated extensive-stage small cell lung cancer voluntarily withdrawn. Press release. Published September 25, 2026. Accessed September 28, 2026. https://www.merck.com/news/ifinatamab-deruxtecan-biologics-license-application-for-certain-patients-with-previously-treated-extensive-stage-small-cell-lung-cancer-voluntarily-withdrawn/
2. Ifinatamab deruxtecan (I-DXd) in subjects with extensive disease small cell lung cancer (IDeate-Lung01). ClinicalTrials.gov; NCT05280470. Updated February 25, 2026. Accessed September 28, 2026. https://clinicaltrials.gov/study/NCT05280470
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