Ifinatamab Deruxtecan Shows Promising Response Rates in Extensive-Stage Small Cell Lung Cancer Trial

BASKING RIDGE, N.J. & RAHWAY, N.J.--An interim analysis from the dose-optimization segment of the ongoing IDeate-Lung01 phase 2 trial indicates that ifinatamab deruxtecan (I-DXd) continues to exhibit promising objective response rates in patients with pretreated extensive-stage small cell lung cancer (ES-SCLC). These findings were highlighted during a press conference and will be discussed further in an oral presentation at the 2024 World Conference on Lung Cancer (WCLC24) organized by the International Association for the Study of Lung Cancer.

Ifinatamab deruxtecan, a specifically engineered B7-H3 directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and co-developed with Merck, targets a protein prevalent in many cancer types. Small cell lung cancer (SCLC), which represents about 15% of lung cancer cases, is known for its rapid progression to a metastatic stage, resulting in a five-year survival rate of just 3%. Approximately 65% of SCLC tumors express B7-H3, a protein linked to disease advancement and poor prognosis.

Dr. Charles M. Rudin of Memorial Sloan Kettering Cancer Center emphasized the critical need for new treatments for SCLC, noting the rapid disease progression in most patients. He suggested that the interim results from the IDeate-Lung01 trial could signify an important advancement for those with pretreated ES-SCLC, warranting further research.

In the trial, patients received either 12 mg/kg or 8 mg/kg of ifinatamab deruxtecan. The 12 mg/kg cohort demonstrated a confirmed objective response rate (ORR) of 54.8%, while the 8 mg/kg cohort had an ORR of 26.1%. The median duration of response was 4.2 months for the 12 mg/kg group and 7.9 months for the 8 mg/kg group. Additionally, the disease control rate (DCR) was 90.5% in the 12 mg/kg cohort and 80.4% in the 8 mg/kg cohort. Based on these outcomes, the 12 mg/kg dose will be used in the dose expansion part of the trial.

Patients showed a median progression-free survival (PFS) of 5.5 months and 4.2 months and a median overall survival (OS) of 11.8 months and 9.4 months for the 12 mg/kg and 8 mg/kg doses, respectively. Notably, ifinatamab deruxtecan showed potential effectiveness even in patients with brain metastases, with intracranial ORRs of 50% and 66.7% in the respective cohorts.

Dr. Mark Rutstein from Daiichi Sankyo highlighted the potential of ifinatamab deruxtecan to significantly improve outcomes for ES-SCLC patients, pointing to the nearly one-year median overall survival and observed intracranial responses. The extension of the IDeate-Lung01 trial and the upcoming IDeate-Lung02 phase 3 trial aim to further explore these promising results.

Dr. Marjorie Green from Merck expressed optimism about targeting B7-H3 in small cell lung cancer, emphasizing the significant unmet needs in this patient population. The trial's safety profile was consistent with previous studies of ifinatamab deruxtecan with no new safety signals. Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported in 50% and 43.5% of patients in the 12 mg/kg and 8 mg/kg cohorts, respectively, with common TEAEs including nausea, decreased appetite, anemia, and neutropenia. A small percentage of patients (11.9% in the 12 mg/kg group and 8.7% in the 8 mg/kg group) experienced interstitial lung disease (ILD)/pneumonitis.

Patients in the IDeate-Lung01 trial had typically received a median of two prior therapy lines, including immunotherapy. The median treatment duration was 4.7 months for the 12 mg/kg cohort and 3.5 months for the 8 mg/kg cohort.

In summary, the IDeate-Lung01 trial results underscore ifinatamab deruxtecan's potential as a novel treatment for pretreated ES-SCLC. The study's promising objective response rates, notable duration of response, and overall survival rates indicate a significant step forward in SCLC therapy. Further data from ongoing and future trials will be crucial in confirming these findings and potentially offering a new standard of care for this challenging cancer type.

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