Merck and Daiichi Sankyo Withdraw FDA Submission for Small Cell Lung Cancer Drug After Insufficient Phase 2 Data

Merck and Daiichi Sankyo have withdrawn their request for accelerated FDA approval of ifinatamab deruxtecan (I‑DXd) for adults with extensive‑stage small cell lung cancer that progressed after platinum chemotherapy. The companies announced on Sept. 25 that discussions with the FDA indicated the Phase 2 IDeate‑Lung01 data did not meet the criteria for accelerated approval. The FDA has not disclosed its specific reasons, and the sponsors have not detailed the agency’s concerns. The application had been accepted for priority review in April, according to OncLive.

Response Rates Without a Comparator

Accelerated approval allows the FDA to clear a drug for serious diseases based on early endpoints such as tumor shrinkage that are reasonably likely to predict clinical benefit. Confirmatory trials must later demonstrate that benefit, typically improved overall survival. The pathway speeds patient access but requires a robust early signal.

In the primary analysis published in the Journal of Clinical Oncology, 137 patients receiving the 12 mg/kg dose achieved a confirmed response rate of 48.2 %. Median duration of response was 5.3 months, median progression‑free survival was 4.9 months, and an estimated 59.1 % of patients were alive at nine months.

These results attracted interest, yet the study compared two dose levels of I‑DXd without a control arm, making it difficult to gauge the drug’s true survival impact. The lack of a comparator group underscores the importance of confirmatory data, though the FDA has not explained its decision.

Safety signals were notable. At the 12 mg/kg dose, 62 % of patients experienced grade 3 adverse events and 39.4 % had serious adverse events, per OncLive. Eleven‑point‑seven percent of patients had treatment‑related deaths, a figure that includes deaths not definitively linked to the drug. Patients with a history of steroid‑requiring lung inflammation were excluded from enrollment.

“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 Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, at Merck Research Laboratories.

Phase 3 Trial Holds the Key

The next pivotal study is the Phase 3 IDeate‑Lung02 trial, which randomizes I‑DXd against a physician’s choice of chemotherapy (amrubicin, lurbinectedin, or topotecan) in patients whose disease recurred after one prior platinum regimen. The primary endpoint is overall survival.

Enrollment target is 540 patients, with primary completion projected for January 2028, according to OncLive. Dr. Abderrahmane Laadem, head of therapeutic area oncology development at Daiichi Sankyo, indicated that enrollment is near completion and that a future FDA filing will be considered based on those results.

The withdrawal also impacts a major collaboration. Merck paid Daiichi $4 billion upfront in 2023 for rights to three antibody‑drug conjugate programs, Fierce Biotech reported. One of those assets, patritumab deruxtecan, received an FDA rejection in 2024 over manufacturing concerns and was withdrawn in 2025. I‑DXd is also being tested in Phase 3 studies for prostate and esophageal cancers.

Current Treatment Options

Patients with relapsed extensive‑stage small cell lung cancer still have approved alternatives. Amgen’s Imdelltra (a T‑cell engager) is approved for disease that progressed on or after platinum chemotherapy, and chemotherapy agents such as topotecan and lurbinectedin remain in use. Selection depends on disease kinetics, patient performance status, and prior therapies.

The pipeline remains active. GSK is advancing a B7‑H3‑targeted antibody‑drug conjugate that competes with I‑DXd, Fierce Biotech noted. Even when a candidate stalls, ongoing trials provide patients with access to investigational therapies.

Small cell lung cancer is closely linked to smoking, typically affecting older adults who may have cardiopulmonary comorbidities that influence treatment tolerance. Balancing efficacy with toxicity and quality of life is essential.

For those interested in I‑DXd, participation in clinical trials or the Daiichi Sankyo medical‑access program may be options. Resources such as ClinicalTrials.gov list trial sites, including UT Southwestern Medical Center, Duke Cancer Institute, and HealthPartners. Patients should discuss eligibility with their oncology team and verify current availability.

Caregivers preparing for these discussions should collect pathology reports, prior treatment dates, and recent imaging. New shortness of breath, persistent cough, or fever during therapy warrant prompt reporting, and severe respiratory distress or chest pain requires emergency care.

Financial considerations also matter. Oncology financial counselors can help explore coverage for trial‑related care and manufacturer assistance programs for approved drugs.

The drug remains unapproved, and definitive survival data are not expected until at least 2028. Patients are encouraged to make treatment decisions with their clinicians rather than awaiting a future filing.

Key Questions Answered

What happened? Merck and Daiichi Sankyo withdrew their application for accelerated approval of I‑DXd in extensive‑stage small cell lung cancer after FDA discussions indicated the Phase 2 data were insufficient.

Did the FDA explain why? No public explanation has been released; the companies noted the FDA’s indication that the data did not meet accelerated‑approval standards.

Can patients still get I‑DXd? Eligibility may exist through ongoing clinical trials or Daiichi Sankyo’s medical‑access program; patients should consult their oncologist.

What treatments are approved now? Options include Amgen’s Imdelltra, topotecan, and lurbinectedin, with selection guided by individual patient factors.

When could the drug return to the FDA? The sponsors may resubmit after results from the Phase 3 IDeate‑Lung02 trial, which is expected to complete primary analysis in January 2028.

What side effects were seen? In the Phase 2 study, 62 % of patients on the higher dose experienced grade 3 adverse events, and 39.4 % had serious events, with treatment‑related deaths reported in 11.7 % of participants.

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