A Phase II Clinical Study of Fruquintinib Combined With RC48 in the Treatment of Previously Treated HER2-positive Locally Advanced or Metastatic Gastric or Gastroesophageal Junction (G/GEJ) Cancer

A Multicenter, Open Label，Single Arm，Phase II Study to Evaluate the Effect and Safety Fruquintinib Combined With RC48 in the Treatment of Previously Treated HER2-positive Locally Advanced or Metastatic Gastric or Gastroesophageal Junction (G/GEJ) Cancer

Although Pembrolizumab plus trastuzumab and chemotherapy is the standard of care for first-line treatment of HER2-positive advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer,there is no established therapy in the second-line setting.

RC48 showed promising activity with manageable safety in patients with HER2-overexpressing, advanced G/GEJ cancer who have previously received at least two lines of chemotherapy.Fruquintinib in combination with Paclitaxel demonstrated encouraging preliminary clinical antitumor activity in patients with advanced GC in ph1b/2 study.

This study is aimed to evaluate the efficacy and safety of Fruquintinib in combination with RC48 in the treatment of previously treated HER2-positive locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Fruquintinib + RC48

Detailed Description

This study is a phase II, single arm study with main purpose to evaluate the safety, tolerability and efficacy of Fruquintinib in combination with RC48 in the treatment of previously treated HER2-positive locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer.

All eligible patients received Fruquintinib (4mg orally, once daily for 3 wks on/1 wk off) combined with of RC48( 2.5mg/kg by intravenous infusion during 30-90 min every 2 weeks) until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

• Study Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18-75years (inclusive);
2. Body weight ≥40 kg;
3. Physical status score (ECOG score) 0-1;
4. Expected survival >12 weeks.;
5. At least one measurable lesion (according to RECIST1.1);
6. Histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic HER2 positive G/GEJ cancer;
7. HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor;
8. Fail in previous first-line standard chemotherapy;
9. prior therapy does not need to have included a HER2-directed therapy;
10. Adjuvant or neoadjuvant therapy for AGC is allowed.
11. Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would contraindicate adjuvant chemotherapy 8. Adequate hematological function defined by absolute neutrophil count (ANC) ≥1.5 × 109/L, platelet count ≥100 × 109/L, and hemoglobin ≥9 g/dL (blood transfusion before recruitment is allowed)
12. Adequate hepatic function defined by a total bilirubin level ≤1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤2.5 × ULN 10. Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) 11. Negative serum or urine pregnancy test at screening for women of childbearing potential 12. Fertile men and women must agree to take highly effective contraceptive precautions during, and for 6 months after the last dose of chemotherapy or for 1 month after the last dose of Tislelizumab

Exclusion Criteria:

1. An interval shorter than 21 days from the last dose of chemotherapy or HER2-directed therapy until the time of randomization
2. Prior treatment with RC48, Fruquintinib, or apatinib either as single agents or as part of a treatment regimen.
3. Treatment with any investigational anticancer drug within 21 days of the first study treatment administration
4. More than one prior line of therapy for advanced G/GEJ cancer;
5. History of other malignancy within the previous 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome
6. Brain metastases that are untreated or symptomatic or require any radiation, surgery, or steroid therapy to control symptoms from brain metastases within 1 month of randomization
7. Peripheral neuropathy Grade >/=2
8. Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, serious cardiac arrhythmia)
9. Other current, severe, uncontrolled systemic disease (e.g., clinically significant metabolic disease, wound healing disorders, ulcers)
10. Clinically significant bleeding within 30 days before enrollment
11. For female participants, current pregnancy or lactation
12. Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
13. Infection with Human immunodeficiency virus (HIV) or hepatitis B virus, hepatitis C virus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fruquintinib + RC48	Drug: Fruquintinib + RC48; Fruquintinib (4mg orally, once daily for 3 wks on/1 wk off) combined with of RC48( 2.5mg/kg by intravenous infusion during 30-90 min every 2 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Tumor assessment will be performed using radiography method every 8 weeks, until the occurrence of progressive disease (PD), using RECIST v 1.1	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	every two months follow up after EOT observation period at 30 days after the last medication	from randomization until death due to any cause, assessed up to 3 year
Objective response rate (ORR)	Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Disease control rate (DCR)	Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Safety and tolerance evaluated by incidence, severity and outcomes of AEs	Safety and tolerance will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.03	from first dose to 30 days post the last dose

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 7, 2022
• Primary Completion (Anticipated): May 7, 2023
• Study Completion (Anticipated): May 7, 2025

Study Registration Dates

• First Submitted: February 6, 2022
• First Submitted That Met QC Criteria: February 6, 2022
• First Posted (Actual): February 16, 2022

Study Record Updates

• Last Update Posted (Actual): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 6, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Fruquintinib，RC48，G/GEJ cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: HMPL-013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No