Blog

Infinatamab deruxtecan (I-DXd) demonstrated intracranial efficacy with acceptable safety in patients with extensive-stage small cell lung cancer (ES-SCLC) and baseline brain metastases, according to data from the primary analysis of the phase 2 IDeate-Lung01 trial (NCT05280470) presented during the 2025 ESMO Congress.¹

In those with baseline brain metastases (n = 65), the intracranial confirmed objective response rate (cORR) was 46.2% (95% CI, 33.7%-59.0%). Specifically, 30.8% of patients achieved a complete response (CR) as their best overall response, 15.4% experienced a partial response (PR), and 44.6% had stable disease (SD); 1.5% of patients experienced progressive disease (PD), and 7.7% were not evaluable (NE). The confirmed disease control rate (cDCR) was 90.8% (95% CI, 81.0%-96.5%). The median duration of response (DOR) was 6.2 months (95% CI, 4.0-7.9), and the median time to response (TTR) was 1.4 months (range, 0.9-8.5).

Moreover, in patients who had not previously received brain radiotherapy for baseline brain metastases (n = 26), I-DXd elicited an intracranial cORR of 57.7% (95% CI, 36.9%-76.6%). In those with baseline brain target lesions (n = 29), the intracranial cORR with the agent was 65.5% (95% CI, 45.7%-82.1%), and the central nervous system (CNS) cDCR was 96.6% (95% CI, 82.2%-99.9%).

“Intracranial efficacy with I-DXd [at] 12 mg/kg was promising, with 30.8% of patients achieving an intracranial CR, contributing to an intracranial cORR of 46.2% and DCR of 90.8%,” Pedro Simoes da Rocha, MD, PhD, said in a presentation of the data. Rocha is a medical oncologist at Vall d’Hebron University Hospital in Barcelona, Spain, and an International Association for the Study of Lung Cancer (IASLC) SCLC committee member.

What Did IDeate-Lung01 Examine?

The multicenter, randomized, open-label, phase 2 study included patients with histologically or cytologically documented ES-SCLC who were at least 18 years of age, had an ECOG performance status no higher than 1, and had previously received at least 1 but no more than 3 lines of platinum-based chemotherapy.² Patients must have experienced radiologically documented disease progression on or after their most recent previous systemic treatment; they also needed to have at least 1 measurable lesion by RECIST 1.1 criteria. Those with asymptomatic brain metastases were allowed.

For part 1 of the study, the dose-optimization portion of the research, patients were randomly assigned 1:1 to receive I-DXd at 8 mg/kg every 3 weeks (n = 46; arm 1) or at 12 mg/kg every 3 weeks. For part 2, the extension portion, the agent was further examined at the 12-mg/kg dose.

The primary end point was ORR by blinded independent central review (BICR), and secondary end points included DOR, progression-free survival (PFS), DCR, and TTR by BICR and investigator assessment. Other end points comprised overall survival (OS), investigator-assessed ORR, safety, pharmacokinetics, and immunogenicity.

Prior data from the IDeate-Lung01 study shared during the IASLC 2025 World Conference on Lung Cancer indicated that when I-DXd was given at a dose of 12 mg/kg every 3 weeks (n = 137), it elicited a systemic cORR of 48.2% (95% CI, 39.6%-56.9%). The DCR was 87.6% (95% CI, 80.9%-92.6%). The median TTR was 1.4 months (range, 1.0-8.1), and the median DOR was 5.3 months (95% CI, 4.0-6.5). Moreover, the median PFS was 4.9 months (95% CI, 4.2-5.5), and the median OS was 10.3 months (95% CI, 9.1-13.3).

A subgroup analysis of patients with asymptomatic brain metastases identified by CNS BICR at study baseline was conducted and shared during the 2025 ESMO Congress.¹ Brain CT or MRI was done at baseline for all patients. Those determined to have brain metastases had brain CT/MRI every 6 weeks for 36 weeks and every 12 weeks thereafter.

What Did the Patient Population Look Like in IDeate-Lung01?

Of the 137 total patients who received I-DXd at a dose of 12 mg/kg, 65 had baseline brain metastases, and 72 did not. Of those who did, 39 received prior brain radiotherapy, and 26 did not. A total of 29 patients had brain target lesions at baseline with a median size of 17 mm (range, 10-68); 15 of these patients had prior brain radiotherapy and 14 did not.

The median patient age was 61.0 years (range, 39.0-76.0). Moreover, 80.0% of patients had an ECOG performance status of 1, and 20.0% had a status of 0. The median number of prior lines of systemic therapy received was 2 (range, 1-3).

What Was Learned About the Systemic and Intracranial Efficacy of I-DXd in ES-SCLC?

In those with baseline brain metastases, the agent led to a systemic cORR of 46.2% (95% CI, 33.7%-59.0%). Best overall responses included CR (1.5%), PR (44.6%), and SD (43.1%); 7.7% of patients had PD, and 3.1% were NE. The systemic cDCR was 89.2% (95% CI, 79.1%-95.6%), the median DOR was 4.3 months (95% CI, 3.0-5.8), the median TTR was 1.4 months (range, 1.0-8.1), the median PFS was 4.5 months (95% CI, 4.0-5.4) and the median OS was 10.4 months (range, 7.9-15.3).

In those without baseline brain metastases (n = 72), the cORR with the agent was 50.0% (95% CI, 38.0%-62.0%) with best overall responses of CR in 2.8% of patients, PR in 47.2% of patients, and SD in 36.1% of patients; 6.9% of patients had PD, and 6.9% were NE. The cDCR in this group was 86.1% (95% CI, 75.9%-93.1%), the median DOR was 5.9 months (95% CI, 4.0-8.3), the median TTR was 1.4 months (range, 1.2-4.0), the median PFS was 5.4 months (95% CI, 4.2-6.7), and the median OS was 10.1 months (95% CI, 8.4-13.3).

Concordance between systemic and CNS objective response was 75.4%, Rocha said, adding that the concordance between systemic and CNS disease control was 86.2%. “OS and PFS were similar for patients with and without baseline brain metastases,” he said.

I-DXd showed intracranial efficacy irrespective of previous treatment for brain metastases at baseline. In those with prior radiotherapy (n = 39), the cORR was 38.5% (95% CI, 23.4%-55.4%); in those who received prior radiotherapy within 6 months prior to the study (n = 28), the cORR was 39.3% (95% CI, 21.5%-59.4%) and in those who received it 6 months or longer before study (n = 11), the cORR was 36.4% (95% CI, 10.9%-69.2%).

“Progression in the brain was uncommon, suggesting that I-DXd may prevent brain metastases,” Rocha added. Among the 65 patients with baseline brain metastases, 35.4% experienced progression in the brain; in those who had not received prior radiotherapy (n = 26), this rate was 23.1%, and in those who had (n =39), this rate was 43.6%. In those without baseline brain metastases (n = 72), 12.5% experienced progression in the brain.

The agent also elicited responses in those with brain target lesions at baseline (n = 29), he added. The CNS cORR in those without prior radiotherapy (n = 14) was 71.4% (95% CI, 41.9%-91.6%); in those with prior radiotherapy (n = 15), the CNS cORR was 60.0% (95% CI, 32.3%-83.7%). Concordance between systemic and CNS objective response was 69.0%, according to Rocha. The CNS DOR was 5.7 months (95% CI, 4.1-7.1) and the CNS TTR was 1.3 months (range, 0.9-3.0).

What Is the Safety Profile of I-DXd in ES-SCLC and Baseline Brain Metastases?

Any-grade treatment-related adverse effects (TRAEs) were experienced by 87.7% of patients with brain metastases at baseline (n = 65) and 91.7% of those without baseline brain metastases (n = 72); these effects were grade 3 or higher for 30.8% and 41.7% of patients, respectively. They were serious in 10.8% and 25.0% of cases. In those with baseline brain metastases, TRAEs led to dose delay, reduction, or treatment discontinuation for 23.1%, 15.4%, and 7.7% of patients; in those without baseline brain metastases, these rates were 27.8%, 15.3%, and 11.1%. TRAEs proved fatal for 1.5% and 6.9% of patients, respectively.

The most common TRAEs experienced by at least 10% of patients with baseline brain metastases were nausea (any grade, 49.2%; grade ≥3, 1.5%), decreased appetite (32.3%; 1.5%), neutropenia (30.8%; 6.2%), anemia (27.7%; 7.7%), asthenia (23.1%; 1.5%), fatigue (20.0%; 3.1%), lymphopenia (20.0%; 12.3%), diarrhea (16.9%; 0%), leukopenia (15.4%; 0%), thrombocytopenia (13.8%; 6.2%), increased aspartate aminotransferase level (10.8%; 1.5%), constipation (10.8%; 0%), and pneumonitis (10.8%; 0%).

What Is Next for I-DXd?

The phase 3 IDeate-Lung02 study (NCT06203210) will be evaluating the intracranial activity of I-DXd vs physician’s choice of treatment in the form of topotecan, amrubicin, or lurbinectedin (Zepzelca) in patients with relapsed SCLC.³

References

1. Simoes da Rocha PF, Kim YJ, Han J-Y, et al. Intracranial activity of ifinatamab deruxtecan (I-DXd) in patients (pts) with extensive-stage (ES) small cell lung cancer (SCLC) and baseline (BL) brain metastases (BM): Primary analysis of IDeate-Lung01. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 2760MO.
2. 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: International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract OA06.03.
3. A study of Ifinatamab deruxtecan versus treatment of physician’s choice in subjects with relapsed small cell lung cancer (IDeate-Lung02). Clinical Trials.gov. Updated August 7, 2025. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT06203210