Treatment with the antibody drug-conjugate ifinatamab deruxtecan (I-DXd) has demonstrated promising activity in pretreated patients with extensive-stage small cell lung cancer (SCLC), particularly those treated at a higher dose. These findings come from an interim analysis of the phase II IDeate-Lung01 study, presented at the World Conference on Lung Cancer in San Diego.
IDeate-Lung01 Trial Results
The dose optimization part of the study evaluated two doses of I-DXd. The cohort of patients who received I-DXd 12 mg/kg had a confirmed objective response rate (ORR) of 54.8%, significantly higher than the 26.1% ORR observed in the cohort who received I-DXd 8 mg/kg, according to Charles Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center.
The disease control rate was also notably higher in the 12-mg/kg group, at 90.5% compared to 80.4% in the 8-mg/kg group. Rudin noted that these rates are "quite impressive for this patient population," especially considering the study included patients who had received multiple lines of therapy for metastatic SCLC.
Median time to response was 1.4 months with both doses. 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.
Intracranial Activity
Rudin noted that the drug showed intracranial activity, which is "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 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."
Safety Profile
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.
Ongoing Phase III Trial
I-DXd at 12 mg/kg is currently being evaluated in the ongoing phase III IDeate-Lung02 trial.
