What clinops professionals need to know
The Phase II IDeate-Lung01 trial showed that ifinatamab deruxtecan achieved a confirmed objective response rate of 48.2% in previously treated extensive-stage small cell lung cancer, with a median duration of response of 5.3 months, progression-free survival of 4.9 months, and overall survival of 10.3 months. Strong activity was also seen in second-line patients, with a 56.3% response rate, and among those with brain metastases, where intracranial response reached 46.2%. Based on these results and earlier supporting data, the FDA granted the therapy Breakthrough Therapy Designation in August 2025.
Merck has shared positive results from the Phase II IDeate-Lung01 trial (NCT05280470) evaluating ifinatamab deruxtecan (I-DXd) in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC).1
The potential first-in-class B7-H3 directed DXd antibody drug conjugate demonstrated a confirmed objective response rate (ORR) of 48.2% in 137 patients, including 3 complete and 63 partial responses. Full results from the study were presented at the 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer.
In a press release, Myung-Ju Ahn, MD, PhD, professor, department of hematology & oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, said: “Patients with extensive-stage small cell lung cancer have an extremely poor prognosis despite current standard of care treatment options. The impressive response rates observed in IDeate-Lung01 provide further evidence of the potential role that ifinatamab deruxtecan could play in treating this aggressive form of lung cancer.”
Key efficacy outcomes from IDeate-Lung01
Additional results from this readout of IDeate-Lung01 revealed:
- Median duration of response (DoR) was 5.3 months (95% CI: 4.0–6.5), with a disease control rate of 87.6% (95% CI: 80.9–92.6).
- Median progression-free survival (PFS) was 4.9 months (95% CI: 4.2–5.5) and median overall survival was 10.3 months (95% CI: 9.1–13.3).
- In the second-line subgroup (n=32), confirmed ORR was 56.3% (95% CI: 37.7–73.6), median duration of response was 7.2 months (95% CI: 3.6–NE), disease control rate was 96.9% (95% CI: 83.8–99.9), median PFS was 5.6 months, and median OS was 12.0 months.
- In the third-line and later subgroup (n=105), confirmed ORR was 45.7% (95% CI: 36.0–55.7), including 3 complete and 45 partial responses, with a disease control rate of 84.8% (95% CI: 76.4–91.0).
- In an exploratory analysis of 65 patients with brain metastases at baseline, intracranial ORR was 46.2% (95% CI: 33.7–59.0) per CNS RECIST v1.1.
Regulatory momentum builds for I-DXd
In August, the FDA granted I-DXd Breakthrough Therapy Designation for adult patients with ES-SCLC whose disease has progressed following platinum-based chemotherapy. In addition to results from IDeate-Lung01, the designation was given based on data from the Phase I/II IDeate-PanTumor01 trial (NCT04145622).2
In a press release from the time, Eliav Barr, MD, SVP, head, global clinical development, chief medical officer, Merck Research Laboratories, said: “Patients living with extensive-stage small cell lung cancer often have limited therapeutic options following disease progression after standard of care treatments. 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.”
Trial design highlights global enrollment and endpoints
IDeate-Lung01 is a global, multicenter, randomized, open-label Phase II trial evaluating I-DXd in ES-SCLC patients previously treated with at least one prior platinum-based regimen and up to three prior lines of therapy.
- Patients with asymptomatic brain metastases, either untreated or previously treated, were eligible.
- In the dose optimization phase, patients were randomized 1:1 to receive I-DXd 8 mg/kg or 12 mg/kg intravenously every three weeks.
- In the dose expansion phase, all patients received the 12 mg/kg dose on the same schedule.
- The primary endpoint was ORR by blinded independent central review per RECIST v1.1.
- Secondary endpoints included DoR, PFS, disease control rate, time to response, overall survival, pharmacokinetics, and safety.
- Intracranial objective response rate was assessed as an exploratory endpoint.
- A total of 187 patients were enrolled across Asia, Europe, and North America.
References
1. Ifinatamab Deruxtecan Demonstrated Clinically Meaningful Response Rates in Patients with Extensive-Stage Small Cell Lung Cancer in IDeate-Lung01 Phase 2 Trial. News release. Merck. September 7, 2025. Accessed September 15, 2025. https://www.merck.com/news/ifinatamab-deruxtecan-demonstrated-clinically-meaningful-response-rates-in-patients-with-extensive-stage-small-cell-lung-cancer-in-ideate-lung01-phase-2-trial/
2. Phase II Trial Data Lead to FDA Breakthrough Therapy Designation for Ifinatamab Deruxtecan in Extensive-Stage Small Cell Lung Cancer. Applied Clinical Trials. August 18, 2025. Accessed September 15, 2025. https://www.appliedclinicaltrialsonline.com/view/phase-ii-trial-data-lead-fda-breakthrough-therapy-designation-ifinatamab-deruxtecan-extensive-stage-small-cell-lung-cancer
.png "BioPharm International")
.png "Pharmaceutical Commerce"){kind=logo}
.png "Turbo Machinery Magazine")
.png){kind=spacer}
