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Treatment with the antibody drug-conjugate ifinatamab deruxtecan (I-DXd) showed promising activity in pretreated patients with extensive-stage small cell lung cancer (SCLC), particularly those treated at a higher dose, according to an interim analysis of the phase II IDeate-Lung01 study.

In the dose optimization part of the study, which evaluated two doses, the cohort of patients who received I-DXd 12 mg/kg had a confirmed objective response rate (ORR) of 54.8% -- more than double the ORR of 26.1% in the cohort who received I-DXd 8 mg/kg, reported Charles Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City, at the World Conference on Lung Cancer in San Diego.

The disease control rate was also higher in the 12-mg/kg group, at 90.5% versus 80.4% in the 8-mg/kg group. Considering this study included patients who have received multiple lines of therapy for metastatic SCLC, these rates "are quite impressive for this patient population," Rudin noted.

Median time to response was 1.4 months with both doses, while the median duration of response was 4.2 months in the 12-mg/kg group and 7.9 months in the 8-mg/kg group.

"Although some of these responses are transient, certainly, there is a patient population here that experienced really durable benefit on this antibody-drug conjugate, with prolonged responses now lasting over a year on treatment," Rudin pointed out.

Median progression-free survival and overall survival were 5.5 months and 11.8 months, respectively, with the higher dose, compared with 4.2 months and 9.4 months with the lower dose.

Patients with extensive-stage SCLC have a very poor prognosis, with limited treatment options. I-DXd is a B7-H3-directed antibody-drug conjugate that showed durable efficacy at doses of ≥6.4 mg/kg, with an ORR of 52.4% and median duration of response of 5.9 months, among 21 patients with extensive-stage SCLC in the phase I/II .

This study enrolled patients with extensive-stage SCLC who received one to three prior lines of treatment, including platinum-based chemotherapy. The study cohort included patients with asymptomatic brain metastases, either treated or untreated.

At data cutoff, 91 patients had been enrolled and 88 treated (46 patients with I-DXd 8 mg/kg, and 42 with 12 mg/kg). The median age of the entire cohort was 64 years, and 72% were men.

Rudin noted that the drug showed intracranial activity, something "really important for patients with small cell lung cancer."

Among patients with brain metastases at baseline, the confirmed ORR was 26.3% among 19 patients in the 8-mg/kg group, and 61.1% among 18 patients in the 12-mg/kg group -- comparable to the ORRs observed in the entire study cohort.

Among patients with brain target lesions at baseline, the intracranial response was "quite impressive," Rudin observed. Specifically, the confirmed intracranial ORR was 66.7% among the six patients who received the lower dose, and 50% among the 10 patients who received the higher dose.

"These are small numbers of patients, but these are real," he added. "I think, importantly, for the management of patients with brain metastases, none of these patients had primary progression in the brain, really suggesting ... that this relatively large small molecule does appear to have CNS [central nervous system] activity."

Most treatment-emergent adverse events were gastrointestinal or hematologic and were more frequent in the 12-mg/kg cohort. Nausea was much more common with the higher dose and led to the initiation of an anti-nausea regimen.

Interstitial lung disease was reported in about 10% of patients overall, with the majority being either grade 1 or 2.

I-DXd at 12 mg/kg is currently being evaluated in the ongoing phase III .

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