Daiichi Sankyo and Merck & Co/MSD have withdrawn their U.S. application seeking accelerated approval of ifinatamab deruxtecan for patients with extensive-stage small cell lung cancer whose disease progressed after platinum-based chemotherapy. Regulatory prospects for the B7-H3-directed antibody-drug conjugate in this disease now depend on a randomized Phase 3 trial that is nearing full enrollment.
Key Takeaways
- The Biologics License Application (BLA) for ifinatamab deruxtecan (I-DXd) in previously treated extensive-stage small cell lung cancer (ES-SCLC) was voluntarily withdrawn on September 25, 2026, ahead of an October 10 FDA action date.[1][2]
- Following discussions with the US Food and Drug Administration (FDA), the companies concluded that the data, including the Phase 2 IDeate-Lung01 trial, did not meet the requirements for accelerated approval.[1]
- Ifinatamab deruxtecan remains investigational and is available only through clinical trials. Approved treatment options in this setting are unaffected.
- The Phase 3 IDeate-Lung02 trial, which compares I-DXd with standard chemotherapy, is expected to form the basis of any future filing.[1]
- Phase 3 development continues in castration-resistant prostate cancer and esophageal squamous cell carcinoma.[1]
Withdraw Accelerated Approval
The application of ifinatamab deruxtecan sought accelerated approval for adults with ES-SCLC whose disease progressed on or after platinum-based chemotherapy. The FDA accepted it in April 2026 under Priority Review, with Real-Time Oncology Review and Project Orbis status. Ifinatamab deruxtecan had previously received Breakthrough Therapy Designation in August 2025.[2][3]
According to the companies, the withdrawal followed discussions with the FDA. Those discussions concluded that the supporting data did not satisfy the requirements for accelerated approval in the proposed indication.[1] Neither the FDA nor the companies have specified which requirement was not met. Accelerated approval allows the FDA to approve a medicine for a serious condition earlier, based on a surrogate endpoint such as tumor response. Two conditions must be met. The new drug must offer a meaningful advantage over available therapies, and additional studies must later confirm clinical benefit.[4]
The withdrawal applies to an application, not to a marketed product. Ifinatamab deruxtecan was never approved in the United States, so no patient currently receiving an approved therapy is affected. Patients with relapsed ES-SCLC can still access I-DXd through ongoing clinical trials, including IDeate-Lung02 (NCT06203210).[1][5]
What is Ifinatamab deruxtecan
Ifinatamab deruxtecan is an antibody-drug conjugate, or ADC, designed to target B7-H3, a protein that is highly expressed in small cell lung cancer and associated with poor prognosis. The drug combines a humanized anti-B7-H3 antibody with a topoisomerase I inhibitor payload (DXd) through a cleavable linker. No B7-H3-directed therapy has been approved for cancer.[1]
The BLA was based primarily on IDeate-Lung01 (NCT05280470), a Phase 2 trial that enrolled 187 patients who had received between one and three prior lines of therapy. In the 137 patients treated at the 12 mg/kg dose, 48.2% had a confirmed tumor response as assessed by blinded independent central review. Responses lasted a median of 5.3 months, and median progression-free survival was 4.9 months.[6]
Among patients with brain metastases at baseline, the intracranial response rate was 46.2%.[7] In the 12 mg/kg group, 62.0% of patients had grade 3 or higher adverse events, and adverse events associated with death were reported in 11.7%. Interstitial lung disease is a recognized risk with DXd-based antibody-drug conjugates.[6][8]
A Changed Treatment Landscape
When the FDA accepted the application, the second-line setting already included a fully approved therapy backed by survival data. In November 2025, tarlatamab (Imdelltra), a DLL3-directed bispecific T-cell engager, received traditional FDA approval for the same patient population. In the Phase 3 DeLLphi-304 trial, tarlatamab extended median overall survival to 13.6 months, compared with 8.3 months with chemotherapy.[9][10]
Within the B7-H3 class, the Phase 3 ARTEMIS-008 trial (NCT06498479) of risvutatug rezetecan, an ADC being developed by Hansoh Pharmaceutical Group in collaboration with GSK, reported an overall survival benefit over topotecan at the 2026 World Conference on Lung Cancer. The trial was conducted in China, and no U.S. application has been filed.[11]
What Comes Next
IDeate-Lung02 is enrolling approximately 540 patients whose disease relapsed after one prior line of platinum-based therapy. Patients are randomized to I-DXd or physician’s choice of topotecan (Hycamtin®; GSK and available in multiple generic brands), amrubicin (Calsed®; Sumito Pharma), or lurbinectedin (Zepzelca®; PharmaMar/Jaxx Pharmaceuticals).[5] The companies have said enrollment is near completion. They will assess a potential filing with the FDA and other regulators once results are available, but they have not given a timeline.[1]
This is the second time the Daiichi Sankyo–Merck collaboration has withdrawn an accelerated approval application for a DXd antibody-drug conjugate in lung cancer. In May 2025, the application for patritumab deruxtecan in EGFR-mutated non-small cell lung cancer was withdrawn after its confirmatory Phase 3 trial did not show a statistically significant overall survival benefit.[12]
Related coverage: For a detailed scientific analysis of the IDeate-Lung01 data and the B7-H3 antibody-drug conjugate landscape, see ADC Review | Journal of Antibody-drug Conjugates.
Clinical Trials
Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01) – ClinicalTrials.gov ID NCT05280470
A Study of Ifinatamab Deruxtecan Versus Treatment of Physician’s Choice in Subjects With Relapsed Small Cell Lung Cancer (IDeate-Lung02) – ClinicalTrials.gov ID NCT06203210
Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer (DeLLphi-304) – ClinicalTrials.gov ID NCT05740566
ARTEMIS-008：HS-20093 Compared With Topotecan in Subjects With Relapsed Small Cell Lung Cancer – ClinicalTrials.gov ID NCT06498479
References
[1] Merck & Co., Inc.; Daiichi Sankyo. Ifinatamab deruxtecan biologics license application for certain patients with previously treated extensive-stage small cell lung cancer voluntarily withdrawn. Press release. September 25, 2026. Last accessed September 25, 2026.
[2] Daiichi Sankyo. Ifinatamab deruxtecan granted priority review in the U.S. for adult patients with previously treated extensive-stage small cell lung cancer who experienced disease progression on or after platinum-based chemotherapy. Press release. April 13, 2026. Last accessed September 25, 2026.
[3] Hofland P. Ifinatamab Deruxtecan Receives FDA Priority Review for Previously Treated Extensive-Stage Small Cell Lung Cancer. ADC Review | J Antibody-drug Conjugates. April 13, 2026. doi: 10.14229/jadc.2026.13.04.009.
[4] U.S. FDA. Guidance for Industry: Expedited Programs for Serious Conditions – Drugs and Biologics. May 2014; 21 CFR 601.41. Online. last accessed on September 25, 2026
[5] Owonikoko TK, Byers L, Cheng Y, Hayashi H, Paz-Ares L, Pérol M, Hu H, Qian M, Garcia CR, Godard J, Tang M, Rudin CM. IDeate-Lung02: a Phase 3 study of second-line ifinatamab deruxtecan in patients with relapsed small cell lung cancer. Future Oncol. 2025 Oct;21(25):3275-3282. doi: 10.1080/14796694.2025.2565995. Epub 2025 Oct 7. PMID: 41055143; PMCID: PMC12536792.
[6] Rudin CM, Johnson ML, Paz-Ares L, Nishio M, Hann CL, Girard N, Rocha P, Hayashi H, Sakai T, Kim YJ, Hu H, Qian M, Singh J, Godard J, Tang M, Ahn MJ. Ifinatamab Deruxtecan in Patients With Extensive-Stage Small Cell Lung Cancer: Primary Analysis of the Phase II IDeate-Lung01 Trial. J Clin Oncol. 2026 Feb;44(4):261-273. doi: 10.1200/JCO-25-02142. PMID: 41086386; PMCID: PMC12834294. [Presentation]
[7] Simoes da Rocha PF, Kim YJ, Han J-Y, et al. Intracranial activity of ifinatamab deruxtecan (I-DXd) in patients with extensive-stage small cell lung cancer and baseline brain metastases: primary analysis of IDeate-Lung01. ESMO Congress 2025; Berlin, Germany. Abstract 2760MO.
[8] Johnson ML, Patel MR, Falchook GS, Koyama T, Gutierrez M, Awad MM, Piha-Paul SA, Friedman CF, Satoh T, Okamoto N, Singh J, Yoshizuka N, Windish HP, Qian M, Tran BP, Doi T. Ifinatamab deruxtecan, a B7-H3-directed antibody-drug conjugate, in patients with advanced solid tumours (IDeate-PanTumor01): dose-escalation results from a phase 1/2 trial. Lancet Oncol. 2026 Apr;27(4):491-501. doi: 10.1016/S1470-2045(25)00733-8. PMID: 41926962.
[9] Amgen. FDA grants full approval to Amgen’s IMDELLTRA® in extensive stage small cell lung cancer. Press release. November 19, 2025. Online. Last accessed September 25, 2026.
[10] Mountzios G, Sun L, Cho BC, Demirci U, Baka S, Gümüş M, Lugini A, Zhu B, Yu Y, Korantzis I, Han JY, Ciuleanu TE, Ahn MJ, Rocha P, Mazières J, Lau SCM, Schuler M, Blackhall F, Yoshida T, Owonikoko TK, Paz-Ares L, Jiang T, Hamidi A, Gauto D, Recondo G, Rudin CM; DeLLphi-304 Investigators. Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. N Engl J Med. 2025 Jul 24;393(4):349-361. doi: 10.1056/NEJMoa2502099. Epub 2025 Jun 2. PMID: 40454646.
[11] Hofland P. Risvutatug Rezetecan Demonstrates Overall Survival Benefit Over Topotecan in Relapsed Small Cell Lung Cancer. ADC Review | J Antibody-drug Conjugates. September 13, 2026. Online. Last accessed on September 25, 2026
[12] Merck & Co., Inc.; Daiichi Sankyo. Patritumab deruxtecan biologics license application for patients with previously treated locally advanced or metastatic EGFR-mutated non-small cell lung cancer voluntarily withdrawn. Press release. May 29, 2025. Online. Last accessed September 25, 2026.
Featured image: © 2026 CHA ONC ADCR. Used with permission.
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