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OncoMatch/Clinical Trials/NCT05274048

Neratinib and Fam-Trastuzumab Deruxtecan in Advanced Gastro-esophageal Cancer Patients

Is NCT05274048 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies multiple treatments including Neratinib Pill and Fam-Trastuzumab Deruxtecan-Nxki (TDxD) for gastric cancer.

Phase 1RecruitingFox Chase Cancer CenterNCT05274048Data as of May 2026

Treatment: Neratinib Pill · Fam-Trastuzumab Deruxtecan-Nxki (TDxD)This is Phase 1 dose finding trial with potential dose expansion to evaluate the safety, toxicity, recommended phase 2 dose (RP2D), and maximum tolerated dose (MTD) of Neratinib plus TDxD using a standard 3+3 dose escalation design in patients with metastatic or unresectable gastro-esophageal cancer that are HER2-overexpressing (IHC 3+ or IHC2+/ISH+) and any other gastrointestinal cancer with HER2 expression with IHC3+. Patients must have progressed or been intolerant of at least one prior line of chemotherapy + HER2 directed therapy.

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Extracted eligibility criteria

Cancer type

Gastric Cancer

Colorectal Cancer

Hepatocellular Carcinoma

Pancreatic Cancer

Cholangiocarcinoma

Esophageal Carcinoma

Biomarker criteria

Required: HER2 (ERBB2) overexpression (IHC 3+ or IHC2+/ISH+ (gastroesophageal cancer); IHC 3+ (other GI cancers))

HER2-overexpressing: (IHC 3+ or IHC2+/ISH+) advanced gastroesophageal cancer (including gastroesophageal junction adenocarcinoma); IHC 3+ for other GI cancers

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Min 1 prior line

Must have received: HER2-targeted therapy — metastatic/unresectable gastroesophageal cancer only

Patients must have received at least one prior line of HER2 directed therapy for metastatic/unresectable disease and completed treatment at least 2 weeks prior to C1D1 (only for Gastroesohageal cancers, not for other GI cancers)

Cannot have received: antibody-drug conjugate (fam-trastuzumab deruxtecan)

must not have received prior treatment with TDxD

Lab requirements

Blood counts

Leukocytes > 3,000/mcL; Absolute neutrophil count > 1,500/mcL; Platelets > 90,000/mcL; Hemoglobin > 9 gm/dl

Kidney function

Creatinine < 2.0mg/dL OR Creatinine clearance > 50 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal

Liver function

Total bilirubin < 2 times institutional normal limits; AST/ALT (SGOT/SGPT) < 5 times institutional normal limits if liver metastases and </+ 2 times institutional normal limits otherwise

Cardiac function

Left Ventricular Ejection Fraction ≥ 45% or lower limit of normal

Patients must have normal organ and marrow function as defined below * Leukocytes > 3,000/mcL * Absolute neutrophil count > 1,500/mcL * Platelets > 90,000/mcL * Hemoglobin > 9 gm/dl * Total bilirubin < 2 times institutional normal limits * AST/ALT (SGOT/SGPT) < 5 times institutional normal limits if liver metastases and </+ 2 times institutional normal limits otherwise * Creatinine < 2.0mg/dL OR * Creatinine clearance > 50 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal Left Ventricular Ejection Fraction ≥ 45% or lower limit of normal.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Stanford Cancer Center · Palo Alto, California
  • Roswell Park Comprehensive Cancer Center · Buffalo, New York
  • Fox Chase Cancer Center · Philadelphia, Pennsylvania

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