Key Takeaways
- Phase III IDeate-Esophageal01 Trial Launches
Merck and Daiichi Sankyo have initiated a global, multicenter Phase III trial evaluating ifinatamab deruxtecan (I-DXd) in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) previously treated with platinum-based chemotherapy and immune checkpoint inhibitors. - I-DXd Targets B7-H3 in Solid Tumors
The investigational antibody-drug conjugate (ADC) I-DXd is designed to target B7-H3, a protein overexpressed in various tumors. Early-phase studies demonstrated clinical activity in ESCC, SCLC, and other solid tumors, supporting advancement into pivotal trials. - Primary Endpoint: Overall Survival
IDeate-Esophageal01 will assess overall survival as the primary endpoint, with secondary endpoints including progression-free survival, objective response rate, and safety, comparing I-DXd to physician’s choice of chemotherapy in approximately 510 patients.
Merck and partner Daiichi Sankyo have initiated the global Phase III IDeate-Esophageal01 trial (NCT06644781) analyzing ifinatamab deruxtecan (I-DXd) in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) whose disease progressed after treatment with platinum-based chemotherapy and immune checkpoint inhibitors.
IDeate-Esophageal01 to Evaluate Ifinatamab Deruxtecan in Post-Platinum ESCC
The first patient in the trial has begun treatment with the novel, potential first-in-class B7-H3 directed antibody-drug conjugate (ADC).1,2
“Patients with metastatic esophageal squamous cell carcinoma continue to experience poor outcomes despite currently available treatments,” 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.”1
Phase I/II Data Support Advancement Across Multiple Tumor Types
I-DXd demonstrated promise treating patients with metastatic lung, prostate, and esophageal cancer in the first-in-human, open-label Phase I/II IDeate-PanTumor01 trial (NCT04145622).3,4
The drug produced the following results:
- A response rate was observed in 32% (95% CI: 24-41) pf patients, with 38 responses (33 confirmed; 28%; 95% CI: 20-37) among 118 patients with various solid tumors, including ESCC, small cell lung cancer (SCLC), squamous non-small cell lung cancer, metastatic castration-resistant prostate cancer, head and neck squamous cell carcinoma, and endometrial cancer at doses ranging from 4.8 mg/kg to 16.0 mg/kg.
- The response rate was 23% (95% CI: 8-45) in the dose escalation and expansion cohorts of patients with ESCC (n=22), producing five responses (four confirmed; 18%; 95% CI: 5-40), a median DOR of 2.8 months (95% CI: 2.6-NR), and a median follow-up of 7.7 months (95% CI: 3.3-10.9).
Novel B7-H3–Targeted ADC Shows Encouraging Early-Phase Activity
I-DXd also produced positive data from an interim analysis of the dose-optimization portion of the ongoing Phase II IDeate-Lung01 trial (NCT05280470), with statistically significant objective response rates in patients with pretreated extensive-stage SCLC (ES-SCLC).5,6
- Patients administered a 12 mg/kg (n = 42) dose of I-DXd achieved a confirmed ORR of 54.8% (95% CI: 38.7-70.2), while patients administered the 8 mg/kg (n=46) dose achieved an ORR of 26.1% (95% CI: 14.3-41.1), as assessed by blinded independent central review (BICR). Among these patients, there were 23 partial responses (PRs) in the 12 mg/kg cohort and one complete response and 11 PRs in the 8 mg/kg cohort.5
- Patients in the 12 mg/kg cohort achieved a median duration of response (DoR) of 4.2 months (95% CI: 3.5-7.0) with a disease control rate (DCR) of 90.5% (95% CI: 77.4-97.3), while patients in the 8 mg/kg cohorts achieved a median DoR of 7.9 months (95% CI: 4.1-NE) with a DCR of 80.4% (95% CI: 66.1-90.6).
Trial Design, Endpoints, and Enrollment Criteria for IDeate-Esophageal01
For the global, multicenter, open-label, randomized IDeate-Esophageal01 trial, investigators will compare the safety and efficacy of I-DXd at a dose of 12 mg/kg to treatment with physician’s choice of chemotherapy with either paclitaxel, docetaxel, or irinotecan hydrochloride.
- The trial will enroll approximately 510 patients with advanced or metastatic ESCC whose disease progressed after being treated with platinum-based chemotherapy therapy and an immune checkpoint inhibitor. Patients who previously received more than one line of systemic therapy in the advanced or metastatic setting will be excluded from enrollment.
- The trial’s primary endpoint is overall survival, with secondary endpoints that include progression-free survival and ORR as assessed by BICR, as well as safety.
Addressing Unmet Needs in Advanced Esophageal Squamous Cell Carcinoma
“Advanced esophageal squamous cell carcinoma is a difficult-to-treat disease, and unfortunately overall survival remains low,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in the release. “The initiation of the pivotal Phase III 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.”1
References
1. IDeate-Esophageal01 Phase 3 Trial of Ifinatamab Deruxtecan Initiated in Certain Patients With Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma. News release. Merck. May 19, 2025. Accessed May 19, 2025. https://www.merck.com/news/ideate-esophageal01-phase-3-trial-of-ifinatamab-deruxtecan-initiated-in-certain-patients-with-pretreated-advanced-or-metastatic-esophageal-squamous-cell-carcinoma/
2. A Study of Ifinatamab Deruxtecan in Subjects With Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) (IDeate-Esophageal01). ClinicalTrials.gov. Updated May 14, 2025. Accessed May 19, 2025. https://clinicaltrials.gov/study/NCT06644781
3. DS-7300 Continues to Show Promising Durable Response in Patients with Several Types of Advanced Cancer. News release. Daiichi Sankyo. September 10, 2022. Accessed May 19, 2025. https://daiichisankyo.us/press-releases/-/article/ds-7300-continues-to-show-promising-durable-response-in-patients-with-several-types-of-advanced-cancer
4. Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors. ClinicalTrials.gov. Updated December 19, 2024. Accessed May 19, 2025. https://clinicaltrials.gov/study/NCT04145622
5. 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 May 19, 2025. 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/
6. Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01). ClinicalTrials.gov. Updated May 14, 2025. Accessed May 19, 2025. https://clinicaltrials.gov/study/NCT05280470
