Merck and Daiichi Sankyo have withdrawn their request for accelerated FDA approval of ifinatamab deruxtecan, or I-DXd, for adults with extensive-stage small cell lung cancer that has worsened after platinum chemotherapy. The companies said on Sept. 25 that discussions with the FDA indicated the supporting data, including results from the Phase 2 IDeate-Lung01 trial, did not meet the requirements for accelerated approval.
The FDA has not published its reasoning, and the companies did not describe the agency's specific concerns. The agency had accepted the application and granted it priority review in April, OncLive reported.
For patients and families, the decision closes a near-term path to a new treatment for a cancer that spreads quickly. About 27,000 people in the U.S. were diagnosed with small cell lung cancer in 2025, according to Merck, and options after first-line chemotherapy remain limited.
Response Rates Without a Comparison Group
Accelerated approval lets the FDA approve a drug for a serious disease based on an early measure, such as tumor shrinkage, that is reasonably likely to predict a real benefit. Companies must then confirm that benefit, often by showing people live longer. The pathway speeds access, but it also means the FDA must be confident that the early signal is meaningful.
In the primary analysis published in the Journal of Clinical Oncology, 137 patients who received the 12 mg/kg dose had a confirmed response rate of 48.2%, meaning their tumors shrank by a set amount. Responses lasted a median of 5.3 months, the median time before the cancer worsened was 4.9 months, and an estimated 59.1% of patients were alive at nine months.
Those numbers drew interest, but the trial compared two doses of I-DXd rather than testing the drug against an existing treatment. Without a control group, it is harder to know how much longer patients live because of the drug. That limitation may help explain why confirmatory data matter, though the FDA has not stated its reasons.
Side effects were also significant. Among patients on the 12 mg/kg dose, 62% had grade 3 adverse events and 39.4% had serious adverse events, according to OncLive. Adverse events associated with death were reported in 11.7% of patients, a figure that includes deaths not necessarily caused by the drug. People with a history of lung inflammation requiring steroids were excluded from the trial.
"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.
The Phase 3 Trial Now Carrying the Weight
The next test is the Phase 3 IDeate-Lung02 trial, which compares I-DXd with a doctor's choice of chemotherapy (amrubicin, lurbinectedin, or topotecan) in people whose cancer returned after one prior platinum-based treatment. Its primary goal is overall survival, the measure that shows whether patients live longer.
The trial aims to enroll 540 patients, with primary completion expected in January 2028, according to OncLive. Dr. Abderrahmane Laadem, head of therapeutic area oncology development at Daiichi Sankyo, said enrollment is near completion and the companies will assess a future FDA filing based on those results.
The withdrawal also sets back a major partnership. Merck paid Daiichi $4 billion upfront in 2023 for rights to three experimental drugs of this type, Fierce Biotech reported. A separate candidate in the deal, patritumab deruxtecan, received an FDA rejection letter in 2024 over a manufacturing inspection, and its application was withdrawn in 2025. I-DXd is also in Phase 3 testing for prostate and esophageal cancers.
Options for Patients and Families Right Now
Patients with relapsed small cell lung cancer still have approved choices. Amgen's Imdelltra, a T-cell engager, is approved for extensive-stage disease that progressed on or after platinum chemotherapy, and chemotherapy drugs such as topotecan and lurbinectedin remain in use. The right option depends on how quickly the cancer returned, overall health, and prior treatment.
The field remains active. GSK is developing a rival drug aimed at the same B7-H3 target, Fierce Biotech noted. For patients, more drugs in testing can mean more trial openings, even when one candidate stalls.
Small cell lung cancer is strongly linked to smoking, and many patients are older adults with heart or lung conditions that affect which treatments they can tolerate. That makes an honest conversation about side effects and quality of life as important as response rates.
People who hoped to receive I-DXd can ask their oncologist about clinical trials. ClinicalTrials.gov also lists a Daiichi Sankyo medical access program for heavily pretreated patients at sites including UT Southwestern Medical Center in Dallas, Duke Cancer Institute, and HealthPartners in Minnesota. Availability can change, so families should confirm current status with the care team.
Caregivers can prepare for that conversation by gathering pathology reports, prior treatment dates, and recent scans. New shortness of breath, a persistent cough, or fever during any treatment should be reported promptly, and severe trouble breathing or chest pain needs emergency care.
Out-of-pocket costs can also shape choices. Patients can ask the oncology team's financial counselor about coverage for trial-related care and about manufacturer assistance programs for approved drugs.
The drug is not approved, full survival results are not expected until at least 2028, and patients should make treatment decisions with their oncology team rather than wait on a future filing.
Key Questions Answered
What happened?
Merck and Daiichi Sankyo withdrew their application for accelerated approval of I-DXd in previously treated extensive-stage small cell lung cancer after FDA discussions.
Did the FDA explain why?
Not publicly. The companies said the FDA indicated the data did not meet accelerated approval requirements.
Can patients still get I-DXd?
Possibly through clinical trials or a listed medical access program. Patients should ask their oncologist about eligibility and current availability.
What treatments are approved now?
Options include Imdelltra and chemotherapy drugs such as topotecan and lurbinectedin, depending on each patient's situation.
When could the drug return to the FDA?
The companies may refile after Phase 3 IDeate-Lung02 results. Primary completion is expected in January 2028.
What side effects were seen?
In the Phase 2 trial, 62% of patients on the higher dose had grade 3 adverse events, and people with prior lung inflammation needing steroids were excluded.
Published by Medicaldaily.com
