A recent study compared two dosages of ifinatamab deruxtecan among patients with extensive-stage small cell lung cancer.
Patients with extensive-stage small cell lung cancer (ES-SCLC) who were heavily pretreated saw benefits from treatments with ifinatamab deruxtecan (I-DXd), trial findings have shown.
This improved efficacy was specifically apparent with a 12 milligram per kilogram (mg/kg) dose versus an 8-mg/kg dose, as shown in an interim analysis of the phase 2 IDeate-Lung 01 trial presented at the 2024 IASLC World Conference on Lung Cancer.
Extensive-stage lung cancer, according to the American Cancer Society, has spread throughout the lung, to the other lung or to other parts of the body.
At a median follow-up of 14.6 months in the 8-mg/kg arm (46 patients) and 15.3 months for the 12-mg/kg dose (42 patients), the confirmed overall response rate (ORR; patients who responded partially or completely to treatment) was 26.1% versus 54.8%, respectively. In the 8-mg/kg arm, the ORR included one complete response (CR, disappearance of cancer; 2.2%) and 11 partial responses (PRs; a decrease in tumor size or extent of cancer in the body; 23.9%). In the 12-mg/kg arm, the 54.8% ORR consisted of all PRs.
However, the median duration of response (DOR) was 7.9 months and 4.2 months in the 8-mg/kg and 12-mg/kg arms, respectively. The disease control rate (DCR; patients whose disease disappeared, shrunk or was stable from treatment) was 80.4% and 90.5% in the 8-mg/kg and 12-mg/kg arms, respectively.
“Disease control rates were excellent, actually, on both arms,” Dr. Charles M. Rudin, a thoracic medical oncologist and deputy director at Memorial Sloan Kettering Cancer Center in New York, said during an oral presentation of results. “I'll point to the 12-mg/kg dose with a disease control rate of 90% — really impressive, I think, in the context of recurrent, metastatic, small cell lung cancer.”
In the phase 2 trial, patients with ES-SCLC (88 patients) were randomly assigned to receive either 8 mg/kg of I-DXd intravenously or 12 mg/kg. Patients enrolled in the trial had ES-SCLC and previously received one to three lines of therapy, including platinum-based chemotherapy, had an ECOG performance status of 0 or 1 (meaning they were potentially limited in strenuous activity but could perform daily tasks) and had at least one measurable lesion. Patients with asymptomatic brain metastases that were untreated or previously untreated were permitted to enroll.
The primary end point was ORR; secondary end points were DOR and progression-free survival (PFS; the time a patient lives without their disease spreading or worsening); overall survival (OS; the time a patient lives, regardless of disease status); DCR; time-to-treatment response; ORR; and safety. The data cutoff date was April 25, 2024. Treatment was ongoing in four patients in each arm.
The median age was 64 years, 71.6% of patients were male, and most patients had an ECOG performance status of 1 (78.4%). Forty-two percent of patients had brain metastasis at baseline. Half of patients had two prior lines of systemic therapy, and slightly more than half had a chemotherapy-free interval of less than 90 days. Patients received either Zepzelca (lurbinectedin; 15.9%), irinotecan or topotecan (35.2%), Imdelltra (tarlatamab; 6.8%) or amrubicin (6.8%) as their select prior anticancer therapy.
Results showed that the confirmed ORR for systemic response was 26.3% and 61.1% in the 8-mg/kg (19 patients) and 12-mg/kg (18 patients) arms, respectively, for patients with brain metastases at baseline. The 26.3% ORR comprised a 5.3% CR rate and a 21.1% PR rate; the stable disease (SD; cancer that is neither increasing or decreasing in severity), progressive disease (PD; cancer that is spreading, growing or getting worse) and not evaluable (NE) rates were 57.9%, 10.5% and 5.3%, respectively. The 61.1% ORR in the 12-mg/kg arm consisted fully of PRs; the SD, PD and NE rates were 27.8%, 11.1% and 0%, respectively.
Among patients with brain target lesions at baseline in the 8-mg/kg (6 patients) and 12-mg/kg arms (10 patients), the confirmed ORR for systemic response was 16.7% and 60%. The 16.7% ORR consisted of one CR; the SD, PD, and NE rates were 50%, 33.3%, and 0%, respectively. The 60% ORR in the 12-mg/kg arm consisted of all PRs; the SD, PD, and NE rates were 30%, 10%, and 0%, respectively.
Also in those with brain target lesions, the intracranial confirmed ORR was 66.7% versus 50% in the same respective arms. The 66.7% ORR had a 33.3% CR rate and a 33.3% PR rate; the SD rate was also 33.3%. The 50% ORR consisted of a 20% CR rate and a 30% PR rate; five patients (50.0%) had SD.
Additional findings showed that the median PFS was 4.2 months compared with 5.5 months in the 8-mg/kg versus 12-mg/kg arms, respectively. The median OS was 9.4 months and 11.8 months, respectively.
Regarding safety in the ES-SCLC patient population, I-DXd was generally well tolerated at both doses. The median treatment duration was 3.5 months and 4.7 months among patients in the 8-mg/kg and 12-mg/kg arms. The median number of treatment cycles were six and 7.5 in the respective arms.
“We have a fair bit of experience with antibody-group conjugates with the deruxtecan payload at this point, and I don't think there were any great surprises here,” Rudin said during the presentation.
Treatment discontinuations in patients from the 8-mg/kg arm were due to grade 3 (severe) pneumonia (one patient), grade 2 (moderate) pneumonitis (inflammation of the lung tissue; one patient), and grade 4 (life-threatening) pulmonary embolism (blood clots; one patient). In the 12-mg/kg arm, discontinuations were due to grade 1 (mild) and grade 3 pneumonia (one patient each), grade 2 pneumonitis (one patient), grade 2 interstitial lung disease (scarring of the lungs; one patient), grade 3 pneumocystis jirovecii pneumonia (fungal infection in the lungs; one patient), grade 4 radiation pneumonitis (one patient), and grade 5 (fatal) septic shock (one patient).
The most common any-grade side effects in 10% or more of the patient population receiving 8 mg/kg and 12 mg/kg of I-DXd included nausea (28.3%; 50%), decreased appetite (17.4%; 42.9%), anemia (13%; 35.7%), decreased neutrophil count/neutropenia (10.9%; 33.3%), decreased white blood cell count (4.3%; 21.4%), asthenia (weakness; 13.0%; 21.4%), infusion-related reactions (6.5%; 14.3%), diarrhea (10.9%; 14.3%), fatigue (13.0%; 14.3%) and vomiting (15.2%; 7.1%).
“Treatment-related [side effects] associated with grade 3 and above were similar, a little bit higher treatment-emergent [side effects] associated with drug discontinuation on the 12-mg/kg dose cohort, perhaps related to longer duration of treatment,” Rudin said. “We can see that the primary adverse effect is really focusing on [gastrointestinal] toxicity and hematologic toxicity, again, not unexpected.”
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