Ifinatamab Deruxtecan Shows High Response Rates for Heavily Pretreated Small Cell Lung Cancer

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Ifinatamab deruxtecan produced promising objective response rates (ORR) in patients with heavily pretreated extensive-stage small cell lung cancer (ES-SCLC), according to findings from an interim analysis of the Phase II IDeate-Lung01 trial (NCT05280470) presented at the 2024 IASLC World Conference on Lung Cancer.^1,2 The potential first-in-class B7-H3 directed antibody drug conjugate co-developed by Daiichi Sankyo and Merck could fill a significant need for patients with SCLC, which has a five-year survival rate of just 3% and limited treatment options.

“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 co-director of the Fiona and Stanley Druckenmiller Center for Lung Cancer Research, said in a press release. “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.”¹

SCLC comprises approximately 15% of total lung cancer cases, as the aggressive disease can quickly progress to metastasis. Approximately 65% of SCLC tumors express the transmembrane protein B7-H3, which binds to the CD28 family of receptors, including PD-1. While the protein has been shown to be overexpressed in several cancer types, its overexpression in SCLC is associated with a poor prognosis. Currently, there are no B7-H3 directed medicines approved for the treatment of any cancer. By the end of 2024, the American Cancer Society estimates approximately 234,580 new cases of lung cancer with 125,070 deaths.³

The global, multicenter, randomized, open-label, two-part IDeate-Lung01 trial is analyzing the safety and efficacy of ifinatamab deruxtecan in patients with ES-SCLC. For the trial’s first part, the dose optimization portion, patients were treated with at least one previous line of platinum-based chemotherapy and up to three lines of prior therapy. Patients were randomly assigned in a 1:1 ratio to receive either 8 mg/kg or 12 mg/kg of ifinatamab deruxtecan.

The trial’s primary endpoint is ORR as assessed by blinded independent central review (BICR). Secondary endpoints include duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to response, and overall safety.

The results showed a confirmed ORR of 54.8% (95% CI: 38.7-70.2) in the ifinatamab deruxtecan 12 mg/kg (n=42) cohort and 26.1% (95% CI: 14.3-41.1) in the 8 mg/kg (n=46) cohort, as assessed by BICR. Investigators observed 23 partial responses (PR) in the 12 mg/kg cohort compared with one complete response and eleven PRs in the 8 mg/kg cohort.

Median DoR was 4.2 months (95% CI: 3.5-7.0) in the 12 mg/kg cohort and 7.9 months in the 8 mg/kg cohort (95% CI: 4.1-NE). DCR was 90.5% (95% CI: 77.4-97.3) in the 12 mg/kg cohort and 80.4% (95% CI: 66.1-90.6) in the 8 mg/kg cohort. Median duration of treatment was 4.7 months for patients in the 12 mg/kg cohort (range, 0.03-15.2) and 3.5 months for the 8 mg/kg cohort (range, 0.03–13.9).

Median PFS was 5.5 months in the 12 mg/kg cohort (95% CI: 4.2-6.7) and 4.2 months in the 8 mg/kg cohort (95% CI: 2.8-5.6). Median OS was 11.8 months in the 12 mg/kg cohort (95% CI: 8.9-15.3) and 9.4 months in the 8 mg/kg cohort (95% CI: 7.8-15.9).

As a result of these findings, investigators selected the 12 mg/kg dose for the dose expansion portion of the trial.

“The (ORR) and median (OS) 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, Oncology Clinical Development, Daiichi Sankyo, said in the press release. “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 where we are evaluating ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer versus treatment of physician’s choice of chemotherapy.”¹

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://www.merck.com/news/ifinatamab-deruxtecan-continues-to-demonstrate-promising-objective-response-rates-in-patients-with-extensive-stage-small-cell-lung-cancer-in-ideate-lung01-phase-2-trial/

2. Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01). ClinicalTrials.gov. June 18, 2024. Accessed September 9, 2024. https://clinicaltrials.gov/study/NCT05280470

3. Key Statistics for Lung Cancer. American Cancer Society. Accessed September 9, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html