Ifinatamab deruxtecan for advanced esophageal squamous cell carcinoma

A Phase 2 Open-Label, Umbrella Platform Design Study of Investigational Agent(s) in Participants With 2L/3L Unresectable Locally Advanced or Metastatic Esophageal Cancer: KEYMAKER-U06 Substudy 06F

This trial will test whether ifinatamab deruxtecan can shrink or eliminate advanced esophageal squamous cell carcinoma in people whose cancer progressed after one or two prior systemic treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Merck Sharp & Dohme LLC (industry)
• Drugs / interventions: ifinatamab
• Locations: 7 sites (Nagoya, Aichi-ken and 6 other locations)
• Trial ID: NCT07405151 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 interventional trial gives ifinatamab deruxtecan (I-DXd), an antibody-drug conjugate, to people with unresectable locally advanced or metastatic esophageal squamous cell carcinoma who have progressed after 1–2 prior systemic therapies. The study enrolls patients with measurable disease and adequate organ function and tracks tumor response rates, specifically how many participants experience tumor shrinkage or disappearance. The protocol is conducted under a master screening framework (KEYMAKER-U06) and includes planned management for adverse events, including rescue medication as needed. Sites are at major cancer centers in Japan and the trial is sponsored by Merck with collaboration from Daiichi Sankyo.

Who should consider this trial

Good fit: Ideal participants have histologically confirmed unresectable locally advanced or metastatic esophageal squamous cell carcinoma with measurable disease, have progressed after one or two prior systemic therapies, and meet required organ function and safety criteria.

Not a fit: Patients with non-squamous histology (adenocarcinoma or adenosquamous), uncontrolled symptomatic effusions, clinically significant corneal disease, recent arterial thromboembolic events, or other protocol exclusions are unlikely to benefit from this trial.

Why it matters

Potential benefit: If effective, I-DXd could produce meaningful tumor shrinkage or remissions for some patients with advanced ESCC who have limited treatment options.

How similar studies have performed: Other antibody-drug conjugates have shown activity in various solid tumors, but use of ifinatamab deruxtecan specifically in ESCC is relatively new and experimental.

Eligibility criteria

Inclusion Criteria:

* Has a histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
* Has disease progression after 1 or 2 prior lines of systemic therapy for unresectable locally advanced or metastatic ESCC
* Has measurable disease
* If infected with human immunodeficiency virus (HIV), has well-controlled HIV on antiretroviral therapy
* Has adequate organ function

Exclusion Criteria:

* Has histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma subtype
* Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention
* Has clinically significant corneal disease
* Has any of the following within 6 months before screening: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event
* If infected with HIV, has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has uncontrolled or significant cardiovascular disease
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system metastases and/or carcinomatous meningitis
* Has a history of (noninfectious) pneumonitis/interstitial lung disease irrespective of requiring steroids or has any current pneumonitis/interstitial lung disease or has suspected pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy other than those permitted.
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc), and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen

Where this trial is running

Nagoya, Aichi-ken and 6 other locations

• Aichi Cancer Center ( Site 2702) — Nagoya, Aichi-ken, Japan (RECRUITING)
• Kanagawa Cancer Center ( Site 2701) — Yokohama, Kanagawa, Japan (RECRUITING)
• National Cancer Center Hospital ( Site 2700) — Chūō, Tokyo, Japan (RECRUITING)
• Asan Medical Center ( Site 2901) — Seoul, South Korea (RECRUITING)
• Samsung Medical Center ( Site 2900) — Seoul, South Korea (RECRUITING)
• Hopitaux Universitaires de Geneve HUG ( Site 3701) — Geneva, Switzerland (RECRUITING)
• National Cheng Kung University Hospital ( Site 3001) — Tainan, Taiwan (RECRUITING)

Study contacts

• Study coordinator: Toll Free Number

Conditions: Oesophageal Squamous Cell Carcinoma