Daiichi Sankyo and Merck Withdraw Lung Cancer ADC Filing Rather Than Risk a Rejection

Ifinatamab deruxtecan (I-DXd)What to know

30-second read

For Oncology · Pulmonology

Who

Patients with relapsed extensive-stage small-cell lung cancer (ES-SCLC) who progressed after platinum-based chemotherapy — the population the withdrawn filing targeted.

What happened

Daiichi Sankyo and Merck voluntarily withdrew their BLA for ifinatamab deruxtecan on 25 September 2026, ahead of an FDA decision due 10 October 2026.

Evidence

Phase 2 IDeate-Lung01 (137 patients): 48.2% objective response, 5.3-month median response duration. The companies say FDA signaled this falls short of the accelerated-approval bar.

Key consideration

FDA paused the Phase 3 confirmatory trial in December 2025 after excess fatal lung toxicity (ILD); whether that, the efficacy data, or both drove this withdrawal is unstated.

No new option yet

Second-line ES-SCLC options are unchanged: lurbinectedin, topotecan, platinum rechallenge and tarlatamab, the newest approved option (DeLLphi-304: 13.6 vs 8.3-month survival).

What’s next

Phase 3 IDeate-Lung02 is nearing full enrollment; the companies say a future filing depends on its results, with no stated timeline.

Practice impactNo change to practice yet

Nothing changes in second-line SCLC treatment today — a near-term option disappeared, not an existing one. Watch IDeate-Lung02's confirmatory results before expecting this drug back before FDA.

Read the full physician analysis

Full analysis · 9 min readOncLive, Fierce Biotech (25 Sep 2026) · IDeate-Lung01 (ClinicalTrials.gov NCT05280470)

Daiichi Sankyo and Merck voluntarily withdrew their Biologics License Application for ifinatamab deruxtecan (I-DXd) in previously treated extensive-stage small-cell lung cancer on 25 September 2026, two weeks before an FDA decision that had been due 10 October. The companies say FDA discussions indicated the Phase 2 data submitted did not meet the bar for accelerated approval — the second of their three jointly developed deruxtecan antibody-drug conjugates to be pulled from U.S. review in sixteen months.

A second DXd withdrawal in sixteen months

Ifinatamab deruxtecan is one of three antibody-drug conjugates Daiichi Sankyo licensed to Merck under an October 2023 collaboration worth up to $22 billion — a $4 billion upfront payment, $1.5 billion in continuation payments and as much as $16.5 billion in milestones, with Daiichi retaining Japan rights and sole manufacturing. The first of the three, patritumab deruxtecan (HER3-DXd), was withdrawn from U.S. review in EGFR-mutant non-small cell lung cancer on 29 May 2025 after its confirmatory trial missed statistical significance on overall survival despite a positive result on progression-free survival. Ifinatamab deruxtecan is the second. The third, raludotatug deruxtecan, remains in earlier-stage development.

Each of the three carries the same deruxtecan payload — a topoisomerase I inhibitor attached by a cleavable linker — that underlies Daiichi Sankyo's approved ADCs Enhertu (HER2-directed) and Datroway (TROP2-directed). Ifinatamab deruxtecan instead targets B7-H3, a protein broadly overexpressed on small-cell lung cancer cells, delivered via a humanized anti-B7-H3 antibody.

What the companies said, and what they didn't

Extensive-stage small-cell lung cancer remains a challenging disease to treat, leaving patients in need of new treatment options. Enrollment in our confirmatory IDeate-Lung02 trial is near completion, and we look forward to assessing the potential for a future filing in this disease based on those results. Abderrahmane Laadem, M.D., Daiichi Sankyo, head of oncology clinical development

That is the companies' own framing, repeated across their disclosures and in trade coverage: FDA “discussions indicated” that the data, including IDeate-Lung01, “do not meet requirements for accelerated approval.” No public FDA statement, complete response letter or refuse-to-file notice has surfaced — because none exists. Withdrawing before a decision date avoids a formal rejection on the public record and keeps the door open to refile once the confirmatory Phase 3 trial reads out. It also means prescribers are working from the sponsors' characterization of FDA's reasoning, not FDA's own words.

The Phase 2 data behind the filing

The withdrawn BLA rested on IDeate-Lung01, a Phase 2, open-label, dose-comparison trial in 187 patients with ES-SCLC who had progressed after at least one platinum-based regimen (up to three prior lines). The efficacy population at the lead 12 mg/kg dose given every three weeks was 137 patients.

IDeate-Lung01 at the 12mg/kg dose (n=137)

48.2%Objective response rate

87.6%Disease control rate

5.3 monthsMedian duration of response

4.9 / 10.3 monthsMedian progression-free survival / median overall survival

As reported in company disclosures and corroborated by OncLive and Targeted Oncology coverage of the 25 September 2026 withdrawal. This is a single-arm Phase 2 readout, not a randomized comparison against standard second-line therapy.

A 48% response rate in a heavily pretreated, historically chemotherapy-refractory population is not a weak result on its face — it is in the range that has supported accelerated approvals in other settings. What the single-arm, dose-comparison design cannot establish is durability or survival benefit relative to an active comparator, which is presumably where FDA's reasoning landed, on the companies' own account.

A safety signal the agency flagged months earlier

In December 2025, FDA placed the Phase 3 confirmatory trial, IDeate-Lung02, on partial clinical hold after a higher-than-expected rate of fatal interstitial lung disease (ILD) events — independently reported by trade press at the time, separate from and three months before this withdrawal. Interstitial lung disease and pneumonitis are an established risk across the deruxtecan payload class; Enhertu and Datroway both carry boxed or prominent ILD warnings on their own labels.

Whether the ILD signal, the magnitude of the efficacy data, or both drove FDA's view of the accelerated-approval application is not something either company or FDA has stated on the record. Prescribers should treat the connection as a reasonable inference from the public timeline, not a confirmed fact: a serious safety signal surfaced on the confirmatory trial three months before the BLA most closely tied to the same drug and payload was withdrawn.

Where this leaves second-line treatment

Second-line-and-beyond options in ES-SCLC

	Ifinatamab deruxtecan	Tarlatamab	Lurbinectedin / topotecan
Status	BLA withdrawn 25 Sep 2026; not approved anywhere	FDA approved, 2024	Approved, established second-line options
Mechanism	B7-H3-directed antibody-drug conjugate	DLL3 x CD3 bispecific T-cell engager	Alkylating agent (lurbinectedin) / topoisomerase inhibitor (topotecan)
Key evidence	IDeate-Lung01 (Phase 2, single-arm): 48.2% ORR, n=137	DeLLphi-304 (Phase 3, randomized vs chemotherapy): OS 13.6 vs 8.3 months	Established trial programs supporting current approvals
Notable safety signal	Fatal ILD events prompted a December 2025 partial clinical hold on the confirmatory trial	Cytokine release syndrome, a T-cell engager class effect	Myelosuppression, well characterized with long use

Tarlatamab particulars from its own FDA-approved label and the DeLLphi-304 publication, not a head-to-head trial against ifinatamab deruxtecan. Prescribe from current labels, not this table.

• No prescribing change. Ifinatamab deruxtecan was never approved; there is nothing to stop using and nothing new to start.
• Tarlatamab remains the newest evidence-based second-line option with randomized, survival-benefit data (DeLLphi-304) already supporting its approval.
• Watch for ILD in any patient on a deruxtecan-class ADC (Enhertu, Datroway) — this withdrawal is a reminder the payload class carries a real pulmonary-toxicity signal, independent of tumor type.
• A future filing is possible, not assured. The companies have tied any resubmission to IDeate-Lung02's Phase 3 results, with no disclosed timeline for when that reads out.

What a resubmission would need

IDeate-Lung02 is the confirmatory Phase 3 trial the original accelerated-approval pathway was always going to require: a randomized comparison of ifinatamab deruxtecan against physician's choice of amrubicin, lurbinectedin or topotecan in relapsed ES-SCLC after one prior platinum-based line. The companies describe enrollment as “near completion.” A positive, randomized survival or response-rate result against an active comparator would address the central gap in IDeate-Lung01 that the single-arm Phase 2 could not — and would also need to show the ILD rate is manageable enough to support an acceptable benefit-risk case, given the clinical hold history. Neither question will be answered before the trial reads out, and neither company has given a date for that.

The honest summary is that a disease with few second-line options did not gain one today, and did not lose one either — ifinatamab deruxtecan was never available to prescribe. What changed is the timeline: a filing that might have reached FDA's decision this month is now tied to a Phase 3 readout with no announced date, against the backdrop of a real pulmonary-toxicity signal the agency had already flagged. Every story on this desk is filed by specialty on the For Physicians front.

Ifinatamab deruxtecan in SCLC, start to withdrawal

1. Oct 2023

   Daiichi Sankyo – Merck collaboration

   Merck licenses co-development and co-commercialization rights to three DXd ADCs, including ifinatamab deruxtecan, in a deal worth up to $22 billion.

2. Aug 2025

   Breakthrough Therapy designation

   Granted for ifinatamab deruxtecan in previously treated ES-SCLC, based on IDeate-Lung01 Phase 2 data.

3. Apr 2026

   Priority Review granted

   FDA accepts the BLA for priority review; PDUFA date set for 10 October 2026.

4. Dec 2025

   IDeate-Lung02 partial clinical hold

   FDA pauses the Phase 3 confirmatory trial after a higher-than-expected rate of fatal ILD events.

5. 25 Sep 2026

   BLA voluntarily withdrawn

   Daiichi Sankyo and Merck pull the filing, citing FDA feedback that the data did not meet the accelerated-approval bar.

6. Not yet disclosed

   IDeate-Lung02 results

   The companies say a future filing depends on this Phase 3 readout.

Frequently asked questions

Does this withdrawal affect any approved treatment for small-cell lung cancer?

No. Ifinatamab deruxtecan was never approved anywhere; this was a withdrawal of a pending application, not a market removal. Current second-line and later options — lurbinectedin, topotecan, platinum rechallenge and tarlatamab — are unchanged.

Why did the companies withdraw instead of waiting for FDA's decision?

Daiichi Sankyo and Merck say FDA discussions indicated the Phase 2 IDeate-Lung01 data did not meet the bar for accelerated approval. Withdrawing avoids a formal complete response letter and preserves the option to refile if the ongoing Phase 3 confirmatory trial succeeds.

Is the interstitial lung disease (ILD) signal specific to this drug, or a class effect?

ILD/pneumonitis is a known risk across the deruxtecan (DXd) payload class, which also includes Enhertu and Datroway. FDA placed ifinatamab deruxtecan's Phase 3 confirmatory trial on partial clinical hold in December 2025 after a higher-than-expected rate of fatal ILD events; whether that signal specifically drove the BLA withdrawal has not been stated by FDA.