First Patient with SCLC Dosed With I-DXd in Phase 3 Study

Lung cancer: © Crystal Light - stock.adobe.com

The first patient in the phase 3 IDeate-Lung02 study (NCT06203210) has been dosed with the investigational antibody-drug conjugate (ADC) ifinatamab deruxtecan (IDXd; DS-7300) for the treatment of relapsed small cell lung cancer (SCLC).¹

“Patients living with small cell lung cancer face poor outcomes with currently available treatments,” said Mark Rutstein, MD, global head of oncology clinical development, Daiichi Sankyo, in a press release. “The IDeate-Lung02 trial is an important next step as we look to better understand the role of ifinatamab deruxtecan as a potential new medicine for patients with certain types of small cell lung cancer.”

I-DXd is a potential first-in-class B7-H3-directed ADC. It is composed of a humanized anti-B7-H3 monoclonal antibody attached to topoisomerase I inhibitor payloads. In April 2023, the FDA granted I-DXd an orphan drug designation.

According to data from a subgroup analysis of the IDeate-PanTumor01 study (NCT04145622) presented at the 2023 IASLC World Conference on Lung Cancer, at median follow-up of 11.7 months, there was a 52.4% objective response rate (ORR) in patients with SCLC (95% CI, 29.8%-74.3%) treated with I-DXd. The median progression-free survival (PFS) was 5.6 months (95% CI, 3.9-8.1).²

Further, almost all patients had a reduction in target lesion size in post-baseline scans, with a median time to response (TTR) of 1.2 months (95% CI, 1.2-1.4). Partial responses were observed in 47.6% and complete responses in 4.8%, confirmed by RECIST v1.1 criteria. The median duration of response (DOR) was 5.9 months (95% CI, 2.8-7.5). At the data cutoff of January 31, 2023, the median overall survival (OS) was 12.2 months (95% CI, 6.4-not evaluable).

About the Phase 3 IDeate-Lung02 Study

The phase 3 study has enrolled an estimated 468 patients across 229 locations and is still recruiting.3 Patients will be randomized to receive 12 mg/kg of I-DXd intravenously on day 1 of each 21-day cycle until unacceptable toxicity or progressive disease or investigator’s choice of topotecan, lurbinectedin, or amrubicin.³

The study’s primary end points are ORR and OS, and secondary end points include PFS, DOR, disease control rate, TTR, quality-of-life, incidence of adverse events, and pharmacokinetics.

Patients are eligible for enrollment in the study if they have histologically or cytologically confirmed SCLC, received at least 2 cycles of therapy (including only 1 prior platinum-based therapy), and an ECOG performance status of 1 or lower. Those who previously received an exatecan-derived ADC, have uncontrolled cardiovascular disease, or has severe pulmonary compromise are not eligible for participation.

REFERENCES:

1. IDeate-Lung02 phase 3 trial of ifinatamab deruxtecan initiated in patients with relapsed small cell lung cancer. News release. Daiichi Sanko. August 1, 2024. Accessed August 1, 2024. https://tinyurl.com/mwctkyav

2. Johnson M, Awad M, Koyama T, et al. Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with refractory SCLC: a subgroup analysis of a phase 1/2 study. Presented at: World Conference on Lung Cancer; September 9-12, 2023; Singapore. Oral abstract OA05.05.

3. A study of ifinatamab deruxtecan versus treatment of physician's choice in subjects with relapsed small cell lung cancer (IDeate-Lung02). ClinicalTrials.gov. Updated July 26, 2024. Accessed August 1, 2024. https://clinicaltrials.gov/study/NCT06203210