First Patient Dosed in Study of I-DXd in Esophageal Cancer
The phase 3 IDeate-Esophageal01 study of ifinatamab deruxtecan has dosed its first patient with esophageal squamous cell carcinoma.
3D rendered medically accurate illustration of esophagus cancer: © Sebastian Kaulitzki - stock.adobe.com
The first patient in the phase 3 IDeate-Esophageal01 study (NCT0664478) evaluating the investigational antibody-drug conjugate (ADC) ifinatamab deruxtecan (I-DXd) in unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) has been dosed.1
“Patients with metastatic esophageal squamous cell carcinoma continue to experience poor outcomes despite currently available treatments,” said Mark Rutstein, MD, Head, Therapeutic Area Oncology Development, Daiichi Sankyo, said in a press release. “The encouraging clinical activity seen in our early-phase signal finding trial supports further evaluation of ifinatamab deruxtecan as a potential treatment strategy for these patients.”
IDeate-Esophageal01 is a global, multicenter, open-label, randomized study evaluating I-DXd vs investigator’s choice of chemotherapy in patients with advanced or metastatic ESCC with disease progression following platinum-based chemotherapy and an immune checkpoint inhibitor. The study plans to enroll approximately 510 patients at sites in North America, Europe, and Asia.
The study’s primary end point is overall survival, and secondary end points include progression-free survival, objective response rate (ORR), duration of response (DOR), disease control rate (DCR), change from baseline in quality of life, incidence of treatment-emergent adverse events (TEAEs), treatment-emergent anti-drug antibodies, and pharmacokinetics.2
“Advanced esophageal squamous cell carcinoma is a difficult-to-treat disease, and unfortunately overall survival remains low,” said Marjorie Green, MD, senior vice president and head of oncology global clinical development, Merck Research Laboratories, in the press release. “The initiation of the pivotal phase 3 IDeate-Esophageal01 clinical trial demonstrates our shared commitment with Daiichi Sankyo to further expand our clinical development program evaluating this potentially first-in-class ADC across multiple solid tumors where there are unmet needs for new treatment options.”
About I-DXd
I-DXd is a potential first-in-class B7-H3-directed ADC. In addition to ESCC, I-DXd is being investigated as a treatment option in extensive-stage small cell lung cancer (SCLC) in the phase 2 IDeate-Lung01 study (NCT05280470), the phase 3 IDeate-Lung02 study (NCT06203210) in relapsed SCLC, and the phase 1b/2 IDeate-Lung03 (NCT04145622) in patients with extensive-stage SCLC in combination with atezolizumab (Tecentriq) with or without carboplatin. Additionally, the phase 2 IDeate-PanTumor02 and phase 1/2 IDeate-PanTumor01 are assessing the agent across multiple tumor types (NCT06330064; NCT04145622).
In findings from an interim analysis of the dose-optimization portion of the IDeate-Lung01 presented at the 2024 World Conference on Lung Cancer, the confirmed ORR was 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. 3,4 A median DOR 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 DCR 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.
Regarding safety, in the 12 mg/kg group, grade 3 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.
I-DXd was previously granted orphan drug designation in the US, EU, Japan, and Taiwan for the treatment of SCLC.1
