FDA Grants Breakthrough Therapy Designation to I-DXd in SCLC

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to Ifinatamab deruxtecan (I-DXd) for the treatment of adults with extensive-stage small cell lung cancer who have experienced disease progression on or after receiving platinum-based chemotherapy, according to a news release from Merck.

“This breakthrough therapy designation granted by the FDA to Ifinatamab deruxtecan highlights the urgent need for new treatment options for patients with pretreated extensive-stage small cell lung cancer,” said Dr. Ken Takeshita, global head, R&D, Daiichi Sankyo, in the news release. “We are committed to advancing this medicine with the goal of bringing the first B7-H3 directed antibody drug conjugate to patients in order to transform the outcomes of those facing this aggressive disease.”

Breakthrough Therapy Designation for Ifinatamab Deruxtecan in Extensive-Stage Small Cell Lung Cancer Supported by Phase 2 IDeate-Lung01 Trial Results

Ifinatamab deruxtecan is a potential first-in-class B7-H3-directed DXd antibody-drug conjugate that was discovered by Daiichi Sankyo, and according to the new release, is being developed jointly by Daiichi Sankyo and Merck.

Breakthrough therapy designation, as explained by the FDA, is a process designed to expedite the development and review of drugs which are intended to treat a serious condition. Moreover, preliminary evidence and data must suggest that the drug may have a substantial improvement over available therapy.

Extensive-stage small cell lung cancer, as explained by the American Cancer Society, is a cancer that has spread widely throughout the lung, to the patient’s other lung or to other parts of the body.

Antibody-drug conjugates, as previously reported by CURE, consist of an antibody that targets a receptor on cancer cells and is linked to a cytotoxic payload. The payload remains stable outside the targeted cell; however, once the conjugate reaches its destination and enters the tumor cell, the linker breaks apart and releases the drug.

The regulatory decision to grant breakthrough therapy designation was based on data from the phase 2 IDeate-Lung01 clinical trial, as well as from the phase 1/2 IDeate-PanTumor01 clinical trial. Results from the primary analysis of the IDeate-Lung01 study, Merck stated, are set to be presented in a late-breaking oral presentation at the IASLC 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, which will be held Sept. 6 to 9 in Barcelona.

“Patients living with extensive-stage small cell lung cancer often have limited therapeutic options following disease progression after standard of care treatments,” Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said in the news release. “This breakthrough therapy designation reinforces our confidence in the promise of Ifinatamab deruxtecan to play an important role in the treatment of extensive-stage small cell lung cancer, and we are looking forward to sharing data at the upcoming IASLC 2025 World Conference on Lung Cancer that show the potential of this novel option.”

Global Phase 2 and First-in-Human Clinical Trials of Ifinatamab Deruxtecan Continue Enrollment, With Completion Dates Expected in 2025 and 2027

IDeate-Lung01 is a global, multicenter, randomized, open-label, two-part phase 2 clinical trial that has enrolled 187 patients in Asia, Europe and North America. The trial is active, with an estimated completion date of Nov. 15, 2025, according to its listing on clinicaltrials.gov.

The IDeate-PanTumor01 trial is a global, multicenter, first-in-human, open-label trial that has enrolled approximately 250 patients in Asia and North America. It is currently recruiting patients, with an estimated primary completion date of Dec. 1, 2025 and an estimated study completion date of March 1, 2027, according to its listing on clinicaltrials.gov.

References

1. “Ifinatamab Deruxtecan Granted Breakthrough Therapy Designation by U.S. FDA for Patients with Pretreated Extensive-Stage Small Cell Lung Cancer,” by Merck. News release, Aug. 18, 2025; https://www.merck.com/news/ifinatamab-deruxtecan-granted-breakthrough-therapy-designation-by-u-s-fda-for-patients-with-pretreated-extensive-stage-small-cell-lung-cancer/
2. “Breakthrough Therapy,” by FDA. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy
3. “Small Cell Lung Cancer Stages,” by American Cancer Society. https://www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/staging-sclc.html
4. “Educated Patient® Lung Cancer Summit Antibody Drug Conjugates Presentation: October 1, 2022,” by Brielle Benyon. CURE, Oct. 16, 2022; https://www.curetoday.com/view/educated-patient-lung-cancer-summit-antibody-drug-conjugates-presentation-october-1-2022
5. “Finding Hope With Antibody-Drug Conjugates in Managing Breast Cancer,” by Alex Biese. CURE, Dec. 5, 2024; https://www.curetoday.com/view/finding-hope-with-antibody-drug-conjugates-in-managing-breast-cancer
6. “Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01);” by clinicaltrials.gov. https://clinicaltrials.gov/study/NCT05280470
7. “Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors);” by clinicaltrials.gov. https://clinicaltrials.gov/study/NCT04145622

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