A Multi-Center, Multi-Cohort Study of the Efficacy and Safety of Anlotinib, TQB2450, and Albumin-bound Paclitaxel in CLDN18.2-regimen-failed Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Peking University1 site in 1 country90 target enrollmentFebruary 25, 2024

ConditionsGastric Cancer Adenocarcinoma of Esophagogastric Junction

InterventionsAnlotinib TQB2450 Albumin-Bound Paclitaxel

DrugsAnlotinib TQB2450 Albumin-Bound Paclitaxel

Overview

Phase: Phase 2
Intervention: Anlotinib
Conditions: Gastric Cancer
Sponsor: Peking University
Enrollment: 90
Locations: 1
Primary Endpoint: ORR
Status: Not yet recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study aims to assess the efficacy and safety of a combination therapy consisting of Anlotinib, TQB2450 (a PD-L1 inhibitor), and Albumin-bound Paclitaxel regimens in patients with advanced gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA) who have failed the previous treatment with Claudin18.2 (CLDN18.2)-related regimens.

Registry

clinicaltrials.gov

Start Date

February 25, 2024

End Date

August 25, 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Peking University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Voluntarily join this study, sign the informed consent form, and have good compliance;
•Pathologically (histologically or cytologically) confirmed HER2/neu-negative (or HER2/neu status unclear) advanced gastric cancer or gastroesophageal junction adenocarcinoma;
•Patients who have failed first-line treatment with CLDN18.2-related regimen (CLDN18.2 drugs include CLDN18.2 monotherapy, CLDN18.2 dual therapy, CLDN18.2 ADC or CLDN18.2 CART therapy, treatment regimen includes CLDN18.2 combined with chemotherapy or immunotherapy or other systemic therapy) and the time from the end of the last treatment with CLDN18.2-related drugs is more than two weeks;
•According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, at least one measurable lesion, which can be accurately measured in at least one direction (the maximum diameter needs to be recorded) by magnetic resonance imaging (MRI) or computed tomography (CT), with the longest diameter at baseline ≥10 mm (if it is a lymph node, the short diameter is required to be ≥15 mm); the measurable lesions should not have received local treatment such as radiotherapy (lesions in the previous radiotherapy area, if confirmed to have progressed and meet the RECIST 1.1 criteria, can also be selected as target lesions);
•Male or female patients aged ≥18 years and ≤75 years;
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0-1;
•Expected survival ≥3 months;
•Adequate organ function, requiring the following laboratory test values at screening:
•Hemoglobin (HB) ≥80g/L (no blood transfusion within 14 days);
•Absolute neutrophil count (ANC) ≥1.5×109/L;

Exclusion Criteria

•For cohort 1, patients who have previously received anlotinib hydrochloride treatment or other anti-angiogenic small molecule tyrosine kinase inhibitors (TKIs) within 6 months. Patients who have stopped treatment with other anti-angiogenic small molecule TKIs for more than 6 months are allowed to enroll; For cohort 2 and cohort 3, patients who have received PD-L1 immune checkpoint inhibitor treatment in the first line are excluded, but patients who have received PD-1 or CTLA-4 immune checkpoint inhibitor treatment in the first line are allowed, if they have any of the following immune-related medical history and treatment history, they are excluded:
•Have any active autoimmune disease or history of autoimmune disease (such as but not limited to autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis; requiring bronchodilators for medical intervention of asthma); but the following patients are allowed to enroll: vitiligo, psoriasis, alopecia that do not require systemic treatment, type I diabetes that is well controlled, hypothyroidism that has normal thyroid function after replacement therapy;
•Diagnosed with immunodeficiency or receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy (dose \>10mg/day of prednisone or other equivalent hormones), and continuing to use it within 2 weeks before the first administration;
•Received any live vaccine, attenuated vaccine (including anti-infective vaccines, such as influenza vaccine, varicella vaccine, etc.), or inactivated vaccine within 4 weeks before enrollment and plan to receive live vaccine/attenuated vaccine/inactivated vaccine during the study; used systemic immunostimulants (including but not limited to interferon and IL-2) within 2 weeks before the start of the study treatment;
•For Cohort 3, patients who have previously received anlotinib hydrochloride or other anti-angiogenic small molecule tyrosine kinase inhibitors (TKIs) within 6 months. Patients who have stopped treatment with other anti-angiogenic small molecule TKIs for more than 6 months are allowed to enroll;
•Patients who have received anti-tumor treatment with traditional Chinese medicine within the past two weeks (the traditional Chinese medicine contains the following medicinal materials such as Brucea javanica, Coix seed, Lentinan, Cantharidin, Toad skin, Astragalus, Sophora, Ugonin, Chebula, Icariin, etc.), but patients who have stopped taking anti-tumor treatment with traditional Chinese medicine for more than two weeks are allowed to enroll;
•Patients who have received ≥1 other systemic systemic anti-tumor treatment (including but not limited to chemotherapy, immunotherapy, targeted therapy, and other systemic treatment regimens) after failing CLDN18.2-related regimen treatment, but palliative local treatment (including radiotherapy and other local treatment regimens) for local lesions (non-target lesions) \>two weeks later are allowed to enroll;
•Patients who have previously received allogeneic bone marrow transplantation or organ transplantation;
•Congenital pulmonary fibrosis, drug-induced pneumonia, organizing pneumonia, or CT-confirmed active pneumonia;
•Patients with symptomatic central nervous system metastases and/or carcinomatous meningitis. Patients with a history of central nervous system metastases or spinal cord compression, if they have received treatment and stopped using anticonvulsants and steroids 4 weeks before the first administration of the study and have clinically stable performance, can enroll in the study;

Arms & Interventions

Anlotinib, TQB2450 and Albumin-bound Paclitaxel

* Cohort 1: Anlotinib + albumin-bound paclitaxel; * Cohort 2: TQB2450 + albumin-bound paclitaxel; * Cohort 3: Anlotinib + TQB2450 + albumin-bound paclitaxel. Anlotinib: 12mg PO, QD, D1-14, Q3W; TQB2450: 1200 mg, IV, D1, Q3W; Albumin-bound paclitaxel: 125mg/m2 IV Day 1,8, Q3W. Until disease progression or intolerable toxicity or patient withdrawal of consent.

Intervention: Anlotinib

Anlotinib, TQB2450 and Albumin-bound Paclitaxel

Intervention: TQB2450

Anlotinib, TQB2450 and Albumin-bound Paclitaxel

Intervention: Albumin-Bound Paclitaxel

Outcomes

Primary Outcomes

ORR

Time Frame: Baseline to CR/PR, about 12 months

Objective Response Rate (ORR) is defined as the percentage of participants who achieve either a complete response (CR) or a partial response (PR) according to the RECIST 1.1 criteria.