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Precision Medicine for Immunotherapy-Resistant Advanced Esophageal Cancer

NCT07653451 · Status: NOT_YET_RECRUITING · Phase: PHASE2/PHASE3 · Type: INTERVENTIONAL · Enrollment: 90

Last updated 2026-06-17

No results posted yet for this study

Summary

This study is an open-label, biomarker-integrated umbrella trial designed to evaluate the clinical efficacy of molecular subtype- and genomic biomarker-guided precision therapies in patients with advanced esophageal cancer refractory to prior immunotherapy. Conducted in a two-step process, the study first enrolls patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have progressed on prior immunotherapy, performing circulating tumor DNA (ctDNA) sequencing to stratify them into three distinct treatment cohorts, after which patients receive tailored combination regimens matched to their specific molecular profiling in the second step. Specifically, Cohort 1 includes patients with high EGFR expression or activation of EGFR-related signaling pathways, who will receive Afatinib (40 mg, p.o., Q.D.) combined with Toripalimab (240 mg, i.v., Q21D) in a 21-day treatment cycle, continuing until radiographic disease progression (PD), unacceptable toxicity, loss to follow-up, death, or other investigator-determined criteria for discontinuation, with a maximum toripalimab treatment duration of 24 months. Cohort 2 comprises patients harboring genomic alterations directly associated with cell cycle regulation or activation of cell cycle signaling pathways, who will be treated with Dalpiciclib (125 mg, p.o., Q.D. for 21 consecutive days followed by a 7-day off period in a 28-day cycle \[Q4W\]) combined with Pyrotinib maleate (320 mg, p.o., Q.D., administered within 30 minutes post-meal, Q4W) until disease progression, unacceptable toxicity, initiation of a new anti-tumor therapy, withdrawal of consent, or investigator's decision for treatment discontinuation. Cohort 3 includes patients with other molecular profiles who do not fit Cohorts 1 or 2, who will receive Camrelizumab (200 mg, i.v., Q3W) and Apatinib (250 mg, p.o., Q.D.), with clinical efficacy evaluations performed every 6 weeks, continuing until radiographic PD, unacceptable toxicity, death, or treatment discontinuation, whichever occurs first. The study aims to recruit an estimated maximum of 90 subjects, enrolling up to 30 subjects per cohort, with the final sample size dependent on the observed toxicities and the prevalence of each molecular cohort within the screened population.

Conditions

Interventions

DRUG

Afatinib + Toripalimab

Patients in this cohort will receive Afatinib at a dose of 40 mg orally (p.o.) once daily (Q.D.) combined with Toripalimab at a dose of 240 mg intravenously (i.v.) every 3 weeks (Q21D). Treatment will continue in 21-day cycles until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. Toripalimab administration is capped at a maximum duration of 24 months.

DRUG

Dalpiciclib + Pyrotinib

Patients will receive Dalpiciclib at a dose of 125 mg p.o. Q.D. for 21 consecutive days followed by a 7-day off period in a 28-day cycle (Q4W), in combination with Pyrotinib maleate at a dose of 320 mg p.o. Q.D. administered within 30 minutes post-meal (Q4W). Treatment will continue until disease progression, unacceptable toxicity, initiation of a new anti-tumor therapy, or withdrawal of consent.

DRUG

Camrelizumab + Apatinib

Patients in this cohort will receive a triple-combination therapy consisting of Camrelizumab (200 mg i.v. every 3 weeks \[Q3W\]), and Apatinib (250 mg p.o. Q.D.). Efficacy evaluations will be performed every 6 weeks. Treatment will continue until radiographic disease progression, unacceptable toxicity, death, or treatment discontinuation, whichever occurs first.

Sponsors & Collaborators

  • Peking University Cancer Hospital & Institute

    lead OTHER

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-07-01
Primary Completion
2027-12-31
Completion
2028-12-31

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07653451 on ClinicalTrials.gov