Daiichi Sankyo, Merck withdraw bid for accelerated approval of I-DXd in small cell lung cancer

Less than two weeks before an expected FDA decision, ifinatamab deruxtecan (I-DXd) is off the U.S. regulatory calendar. Daiichi Sankyo and Merck have withdrawn their application seeking accelerated approval of the drug for extensive-stage small cell lung cancer (ES-SCLC), after the FDA said the data behind it did not meet the bar for that pathway, the companies said in a news release late last week.

The Biologics License Application (BLA) covered adults with ES-SCLC whose disease progressed on or after platinum-based chemotherapy. An FDA decision had been expected by Oct. 10, according to BioPharma Dive.

Accelerated approval lets the FDA clear drugs for serious conditions with unmet need based on early measures, such as tumor shrinkage, before longer-term survival data are in. According to the companies, discussions with the FDA made clear that the data, including results from the phase 2 IDeate-Lung01 trial, do not satisfy the requirements for accelerated approval in the proposed indication.

What IDeate-Lung01 showed

I-DXd is an investigational antibody-drug conjugate (ADC) that targets B7-H3, a protein found at high levels on many cancers, including SCLC. The drug links an antibody to a chemotherapy payload, or a cell-killing drug, so the payload is delivered to tumor cells. It was discovered by Daiichi Sankyo and is being developed jointly with Merck.

IDeate-Lung01 enrolled 187 patients in Asia, Europe and North America who had received at least one and no more than three prior lines of therapy, including platinum-based chemotherapy. The trial did not compare I-DXd with another treatment. In the first part, patients were randomly assigned to one of two doses. In the second part, all patients received the 12 mg/kg dose. The main goal was the share of patients whose tumors shrank, known as the objective response rate (ORR), as judged by independent reviewers.

In the primary analysis presented at the 2025 World Conference on Lung Cancer (WCLC), I-DXd produced an ORR of 48.2% among 137 patients treated at 12 mg/kg. Responses lasted a median of 5.3 months. Median progression-free survival was 4.9 months and median overall survival was 10.3 months. Lung inflammation, called interstitial lung disease (ILD) or pneumonitis, occurred in 12.4% of patients, and two patients (1.5%) died from it.

Phase 3 trial now carries the program

The companies' path forward now runs through IDeate-Lung02. The phase 3 trial compares I-DXd with the physician's choice of chemotherapy (amrubicin, lurbinectedin or topotecan) in patients with relapsed ES-SCLC who have had only one prior line of platinum-based chemotherapy.

However, that trial has faced its own hurdle. The FDA placed it on partial clinical hold in December 2025 after a higher-than-expected number of fatal ILD events, BioSpace reported. The U.S. hold was lifted in January after the companies tightened eligibility criteria and stepped up safety monitoring.

"Extensive-stage small cell lung cancer is a challenging disease to treat, leaving patients in need of new options," Abderrahmane Laadem, M.D., head of therapeutic area oncology development at Daiichi Sankyo, said in the release. "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."

I-DXd is also being tested in two other phase 3 trials, one in castration-resistant prostate cancer and one in esophageal squamous cell carcinoma.

A rising bar in relapsed small cell lung cancer

SCLC is aggressive and spreads quickly. About 27,000 new cases were diagnosed in the U.S. in 2025, or roughly 12% of all lung cancers, according to the companies.

The field I-DXd would enter has shifted in the past year. Amgen's bispecific T-cell engager Imdelltra (tarlatamab-dlle) moved from accelerated to full approval in November 2025, after the phase 3 DeLLphi-304 trial showed a median overall survival of 13.6 months vs. 8.3 months with chemotherapy. This month, a competitor, B7-H3 ADC, risvutatug rezetecan, posted phase 3 ARTEMIS-008 results at WCLC 2026 showing a median overall survival of 18.5 months vs. 10.3 months with topotecan, a 54% lower risk of death, Hansoh Pharma reported.

"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, M.D., senior vice president and head of oncology global clinical development at Merck Research Laboratories, said in the release.