Efficacy of Triplet Combination With Pembrolizumab, Neratinib, and Paclitaxel as a Second Line Treatment in Recurrent/Advanced Gastric Cancer Having Somatic Human Epidermal Growth Factor Receptor Family (EGFR, HER2, HER3, HER4) Mutations or HER2 Amplification/Overexpression

NCT05512182 | Withdrawn Phase 2

• 1 other identifier: 4-2021-1119
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical Indication : HER mutated or HER2 Amplification/Overexpression in Gastric Cancer, 2nd-line Trial Type : Interventional, Open label Treatment Groups : Single arm: Pembrolizumab 200 mg every 3 weeks (Q3W), neratinib at 240 mg once daily (QD), and paclitaxel 175 mg/m2 every 3 weeks (Q3W) Number of trial participants : Approximately 68 patients will be enrolled (with 10% drop-out). Estimated enrollment period : 24 months Estimated duration of trial : It is estimated that the trial will require approximately 30 months from the time the first patient signs the informed consent until the last patient's last visit.

• First Patient In: Mar 2021
• Last Patient In: Feb 2023
• Last Patient Last Visit: Aug 2023 Duration of Participation : 30 months

Conditions

Recurrent/Advanced Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  • To determine the objective response rate (ORR) as a second line treatment in recurrent/advanced gastric cancer with somatic HER2 mutations with or without HER2 amplification/overexpression.

  2 years

Secondary Outcomes (5)

• overall survival (OS)

  2 years

• progression-free survival (PFS)

  2 years

• disease control rate (DCR)

  2 years

• duration of response (DoR)

  2 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v 5.0

  2 years

Study Arms (1)

Chemotherapy

EXPERIMENTAL

Drug: Chemotherapy

Interventions

Chemotherapy DRUG

Pembrolizumab : 200mg/Q3W/IV infusion/Day 1of each 3-week cycle Neratinib : Week 1: 120 mg, Week 2: 160 mg, Week 3 and onwards: 240 mg/QD/Oral/Once daily Paclitaxel : 175mg/m2 /Q3W/IV infusion/Day 1of each 3-week cycle

Chemotherapy

Eligibility Criteria

• Age: 19 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided written informed consent for the trial.
• Is male or female at least 19 years of age on the day of signing informed consent.
• Has a histologically or cytologically confirmed diagnosis of advanced or metastatic gastric adenocarcinoma (systemic metastasis or locally advanced unresectable gastric cancer). A subject must have previously received 1st line chemotherapy using fluoropyrimidine- or platinum-based regimen and showed progression.
• Has tumors with known activating EGFR, ERBB2, ERBB3, ERBB4 mutations or HER2 amplification by NGS, or HER2 overexpression by IHC or SISH/FISH
• Has a life expectancy of at least 3 months.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have measurable or evaluable disease determined by RECIST 1.1.
• Is able to swallow and retain orally administered medication.
• Have adequate organ function as defined in the following table:
• white blood cells ≥3000/mm3 and neutrophils ≥1000/mm3
• platelets ≥100 000/µL
• hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L
• AST (SGOT) and ALT (SGPT) ≤3.0 × upper limit of normal (ULN) of the study site (or ≤5.0 × ULN in patients with liver metastases)
• total bilirubin ≤2.0 × ULN
• creatinine ≤1.5 × ULN or creatinine clearance \>60 mL/min (either measured value or estimated value using the Cockcroft-Gault equation)

You may not qualify if:

• Have received second line or more of anticancer treatment (not including adjuvant chemotherapy).
• Have multiple cancers (with the exception of completely resected basal cell carcinoma, thyroid cancer, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder cancer, and any other cancers that have not recurred for at least 5 years).
• Have history of hypersensitivity to anti-HER2, immune-oncology drugs.
• Have brain or leptomeningeal metastases. Patients may be enrolled for the study if they are asymptomatic and require no treatment.
• Have a tumor with an activating KRAS co-mutation.
• Have a history of uncontrollable or significant cardiovascular disease meeting any of the following:
• myocardial infarction within 180 days before study enrolment
• uncontrollable angina pectoris within 180 days before study enrollment
• New York Heart Association (NYHA) Class III or IV congestive heart failure
• uncontrollable hypertension despite appropriate treatment (e.g., systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg lasting 24 hours or more) arrhythmia requiring treatment.
• Have active, unresolved systemic infection requiring treatment.
• Are contraindicated for pembrolizumab, neratinib, or paclitaxel, or have severe hypersensitivity (≥Grade 3) to any of those drugs and/or their excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Have undergone surgery (any surgery involving general anesthesia) within 28 days before study treatment.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Recurrence

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• SUN YOUNG RHA

  Yonsei Cancer Center, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 23, 2022
• Study Start: September 15, 2022
• Primary Completion: October 30, 2023
• Study Completion: October 30, 2023
• Last Updated: June 15, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)