I-DXd Shows “Impressive” Responses in Extensive-Stage SCLC

"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," according to study author Myung-Ju Ahn, MD, PhD.

Treatment with ifinatamab deruxtecan (I-DXd) yielded “remarkable” efficacy and clinically meaningful responses among previously treated patients with extensive-stage small cell lung cancer (ES-SCLC), according to findings from the phase 2 IDeate-Lung01 trial (NCT05280470) presented at the IASLC 2025 World Conference on Lung Cancer (WCLC).1

Among all patients who received I-DXd at 12 mg/kg (n = 137), the confirmed overall response rate (ORR) was 48.2% (95% CI, 39.6%-56.9%), which included partial responses (PRs) and complete responses (CRs) in 46.0% and 2.2%, respectively. The disease control rate (DCR) in this population was 87.6% (95% CI, 80.9%-92.6%). Additional data revealed that the ORR and DCR, respectively, were 56.3% (95% CI, 37.7%-73.6%) and 96.9% (95% CI, 83.8%-99.9%) among those who received second-line therapy (n = 32) and 45.7% (95% CI, 36.0%-55.7%) and 84.8% (95% CI, 76.4%-91.0%) in patients who received treatment in the third-line setting and beyond (n = 105).

I-DXd yielded a median time to response (TTR) of 1.4 months (range, 1.0-8.1) and a median duration of response (DOR) of 5.3 months (range, 4.0-6.5). Among those who received second-line therapy, the median TTR and DOR were 1.4 months (range, 1.2-4.0) and 7.2 months (95% CI, 3.6-not evaluable [NE]), respectively.

Data showed a median progression-free survival (PFS) of 4.9 months (95% CI, 4.2-5.5) and a median overall survival (OS) of 10.3 months (95% CI, 9.1-13.3) across all patients. Among those who received second-line treatment, the median PFS and OS were 5.6 months (95% CI, 3.9-8.1) and 12.0 months (95% CI, 7.3-19.1), respectively. The study investigators noted that I-DXd produced clinically meaningful ORR benefits across subgroups of patients who received the agent at 12 mg/kg.

“Patients with [ES-SCLC] have an extremely poor prognosis despite current standard-of-care treatment options,” presenting author Myung-Ju Ahn, MD, PhD, a professor in the Department of Hematology & Oncology at Samsung Medical Center of Sungkyunkwan University School of Medicine in Seoul, Republic of Korea, stated in a news release on these data.2 “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.”

Developers engineered I-DXd as a B7-H3–directed antibody drug conjugate that attaches to various topoisomerase I inhibitor payloads through tetrapeptide-based cleavable linkers. The FDA previously granted breakthrough therapy designation to I-DXd as a treatment for patients with ES-SCLC in August 2025.3

In the dose-optimization portion of the multicenter, open-label IDeate-Lung01 study, patients were randomly assigned 1:1 to receive I-DXd at 8 mg/kg (n = 46) or 12 mg/kg every 3 weeks (n = 42). The investigators proceeded with a dose of 12 mg/kg every 3 weeks among 95 patients in the extension portion of the trial.

The trial’s primary end point was ORR per blinded independent central review (BICR). Secondary end points included DOR, PFS, OS, DCR, TTR, safety, pharmacokinetics, and immunogenicity. Investigators also included the end point of intracranial ORR per BICR as part of an exploratory analysis.

Patients 18 years and older with histologically or cytologically confirmed ES-SCLC and at least 1 prior line of platinum-based chemotherapy and no more than 3 prior lines of systemic therapy were eligible for enrollment on the study. Other eligibility criteria included having an ECOG performance status of 0 or 1, radiologically confirmed progressive disease on or after the most recent prior line of systemic treatment, and at least 1 measurable lesion per RECIST v1.1 guidelines.

Across the overall population, the median age was 63 years (range, 34-79), and most patients were male (65.7%) and Asian (48.9%). Additionally, most patients had an ECOG performance status of 1 (77.4%), ES-SCLC at diagnosis (81.0%), a chemotherapy-free interval of 90 days or longer (52.6%), 2 prior lines of therapy (54.7%), and prior anti–PD-(L)1 treatment (81.0%).

Data showed any-grade treatment-related adverse effects (TRAEs) in 89.8% of patients, with grade 3 or higher toxicities affecting 36.5%. TRAEs leading to dose reduction, dose delay, and treatment discontinuation occurred in 25.5%, 15.3%, and 9.5% of patients, respectively. Additionally, 4.4% of patients died due to TRAEs.

Most toxicities were grade 1 or 2; the most common TRAEs of any grade included nausea (43.1%), neutropenia (34.3%), anemia (34.3%), diminished appetite (32.8%), and leukopenia (23.4%). Treatment-related interstitial lung disease or pneumonitis occurred in 12.4% of patients, which consisted of grade 1/2 (8.0%), grade 3 (2.9%), and grade 5 events (1.5%).

References

1. Ahn M-J, Johnson ML, Paz-Ares L, et al. Ifinatamab deruxtecan (I-DXd) in extensive-stage small cell lung cancer: Primary analysis of the phase 2 IDeate-Lung 01 study. Presented at the IASLC 2025 World Conference on Lung Cancer (WCLC). September 6-9, 2025; Barcelona, Spain. Abstract OA06.03.
2. 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://tinyurl.com/mppeybzy
3. Ifinatamab Deruxtecan granted breakthrough therapy designation by U.S. FDA for patients with pretreated extensive-stage small cell lung cancer. News release. Daiichi Sankyo. August 18, 2025. Accessed September 15, 2025. https://tinyurl.com/mudjp42z