Phase 2 Study Reveals Encouraging Results for I-DXd in ES-SCLC

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The antibody-drug conjugate (ADC) ifinatamab deruxtecan (I-DXd) continued to elicit responses in patients with pretreated extensive-stage small cell lung cancer, according to findings from the phase 2 IDeate-Lung01 study (NCT05280470) presented at the 2024 World Conference on Lung Cancer.^1,2

At an interim analysis of the dose-optimization portion of the study, a confirmed objective response rate (ORR) of 54.8% (95% CI, 38.7%-70.2%) was observed in patients receiving the 12 mg/kg dose (n = 42), with 23 partial responses (PRs). An ORR of 26.1% (95% CI, 14.3%-41.1%) was reported in the 8 mg/kg cohort (n = 46), with 11 PRs and 1 complete response (CR).

A median duration of response of 4.2 months (95% CI, 3.5-7.0) was reported in the 12 mg/kg group and 7.9 months (95% CI, 4.1-not estimable) in the 8 mg/kg group. The disease control rate was 90.5% (95% CI, 77.4%-97.3%) and 80.4% (95% CI, 66.1%-90.6%) in the 12 mg/kg and 8 mg/kg groups, respectively.

Among patients with brain target lesions at baseline, the intracranial ORR was 50.0% (95% CI, 18.7%-81.3%) with 2 intracranial CRs, 3 intracranial PRs, and 5 cases of stable disease at 12 mg/kg. At 8 mg/kg, the intracranial ORR was 66.7% (95% CI, 22.3%-95.7%) with 2 intracranial PRs, 2 intracranial PRs, and 2 cases of stable disease.

In the 12 mg/kg group, the median progression-free survival (PFS) was 5.5 months (95% CI, 4.2-6.7), and the median overall survival (OS) was 11.8 months (95% CI, 8.9-15.3). In the 8 mg/kg group, median PFS and OS rates were 4.2 months (95% CI, 2.8-5.6) and 9.4 months (95% CI, 7.8-15.9), respectively.

“Most patients treated for small cell lung cancer experience rapid progression of disease and there is a high unmet need in the advanced setting,” Charles M. Rudin, MD, PhD, deputy director of Memorial Sloan Kettering Cancer Center and codirector of the Fiona and Stanley Druckenmiller Center for Lung Cancer Research, said in a press release.¹ “These interim results from the first part of the IDeate-Lung01 trial suggest that ifinatamab deruxtecan could play an important role in treating patients with pretreated extensive-stage small cell lung cancer and further research is warranted.”

Regarding safety, the observed profile was consistent with previous trials of I-DXd, and no new signals were identified.^1,2 In the 12 mg/kg group, grade 3 treatment-emergent adverse effects (TEAEs) were reported in 50.0% of patients. In the 8 mg/kg group, grade 3 TEAEs were reported in 45.3% of patients. The most common any-grade TEAEs in both groups were nausea (12 mg/kg, 50.0%; 8 mg/kg, 28.3%), decreased appetite (42.9%; 17.4%), anemia (35.7%; 13.0%), neutropenia (33.3%; 10.9%), decreased white blood cell count (21.5%; 4.3%), and asthenia (21.4%; 13.0%).A total of 16.7% of patients in the 12 mg/kg group and 6.5% in the 8 mg/kg group discontinued treatment due to AEs.

“The objective response rate and median overall survival of nearly a year along with the preliminary intracranial responses observed reinforces the potential for ifinatamab deruxtecan to improve outcomes for patients living with this difficult-to-treat type of lung cancer,” said Mark Rutstein, MD, global head of oncology clinical development, Daiichi Sankyo, in a press release.¹ “We look forward to seeing additional results from the extension part of the IDeate-Lung01 phase 2 trial and the recently initiated IDeate-Lung02 phase 3 trial [NCT06203210] where we are evaluating ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer vs treatment of physician’s choice of chemotherapy.”

REFERENCES:

1. Ifinatamab deruxtecan continues to demonstrate promising objective response rates in patients with extensive-stage small cell lung cancer in IDeate-Lung01 phase 2 trial. News release. Merck. September 7, 2024. Accessed September 9, 2024. https://tinyurl.com/4dtf7tj7

2. Rudin C, Ahn, M, Johnson, M, et al. Ifinatamab deruxtecan (I-DXd) in extensive-stage small cell lung cancer (ES-SCLC): interim analysis of IDeate-Lung01. Presented at: 2024 IASLC World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract OA04.03.