The goal of this clinical trial is to learn if Afatinib plus Palbociclib works in previously treated recurrent or metastatic esophageal squamous cell carcinoma. It will also learn about the safety of the combination of Afatinib and Palbociclib. The main questions it aims to answer are:
What is the safe and tolerable dose of Afatinib when combined with 100 mg of Palbociclib (administered orally, three weeks on and one week off)?
Does the combination therapy of Afatinib and Palbociclib induce a tumor response in patients with recurrent or metastatic esophageal squamous cell carcinoma who have received prior treatments?
Age between 18 and 75 years
Histologically or cytologically confirmed as ESCC, locally advanced and unresectable, with local recurrence (local lymph node metastases) or distant metastases
Immunohistochemistry confirmed EGFR(3+) or EGFR-FISH-amplification or next generation sequencing confirmed EGFR-amplification (EGFR expression is not required in Phase 1b, but only patients with EGFR overexpression will be included in Phase 2).
Disease progression after first-line or subsequent lines of therapy.
Patients who have a history of other malignancies in the past five years (except for the cured basal cell carcinoma and cervical carcinoma in situ)
The patient has any active autoimmune disease or a history of autoimmune disease
History of severe allergic reactions or known allergies to macromolecular protein preparations, Afatinib, Palbociclib, or any component of their formulations that have resulted in hospitalization.
Presence of contraindications to Palbociclib or Afatinib.
Single group
Palbociclib
DrugPalbociclib will be given at a dose of 100 mg every day orally with three weeks on and one week off. Four weeks is a cycle.
Afatinib(30mg)
DrugAfatinib will be administered orally at a dose of 30 mg once daily (QD) in each 4-week cycle.
Afatinib(40mg)
DrugAfatinib will be administered orally at a dose of 40 mg once daily (QD) in each 4-week cycle.
Afatinib(RP2D)
DrugIn the Phase 2 study, the recommended Phase 2 dose (RP2D) of Afatinib, determined during the Phase 1b portion, will be utilized.
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Afatinib
Objective Response Rate (ORR)
the proportion of patients with a confirmed complete response or partial response, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Incidence of Treatment-Emergent Adverse Events
Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
Disease Control Rate (DCR)
Percentage of patients who achieve partial response (PR) or complete response (CR) or stable disease (SD) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Progression free survival
the time from treatment initiation to the first disease progression or death from any cause
Overall survival(OS)
the time from treatment initiation until death from any reason
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