Anlotinib, TQB2450 (PD-L1 Inhibitor), and Albumin-bound Paclitaxel Regimens in the Treatment of GC/GEJA

NCT06222944 | Not Yet Recruiting Phase 2

• 1 other identifier: ALTER-GA001
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer; Adenocarcinoma of Esophagogastric Junction

Outcome Measures

Primary Outcomes (1)

• ORR

  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.

  Baseline to CR/PR, about 12 months

Secondary Outcomes (4)

• DCR

  Baseline to CR/PR, about 16 months

• PFS

  Baseline to CR/PR, about 16 months

• OS

  Baseline to CR/PR, about 20 months

• Adverse events

  Baseline to CR/PR, about 20 months

Study Arms (1)

Anlotinib, TQB2450 and Albumin-bound Paclitaxel

EXPERIMENTAL

* 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.

Drug: Anlotinib; Drug: TQB2450; Drug: Albumin-Bound Paclitaxel

Interventions

Anlotinib DRUG

Anlotinib: 12mg PO, QD, D1-14, Q3W;

Also known as: Anlotinib Hydrochloride Capsule

Anlotinib, TQB2450 and Albumin-bound Paclitaxel

TQB2450 DRUG

TQB2450: 1200 mg, IV, D1, Q3W

Anlotinib, TQB2450 and Albumin-bound Paclitaxel

Albumin-Bound Paclitaxel DRUG

125mg/m2 IV D1,8，Q3W

Also known as: Paclitaxel (albumin-bound), Paclitaxel for injection(Albumin Bound)

Anlotinib, TQB2450 and Albumin-bound Paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Platelet count (PLT) ≥75×109/L (no use of interleukin 11 or TPO within 14 days);
• White blood cell count (WBC) ≥3.0×109/L (no use of granulocyte stimulating factor within 14 days).
• Serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN);
• ALT and AST ≤2.5 ULN, if there is liver metastasis, then ALT and AST ≤5×ULN;
• Creatinine (Cr) ≤1.5 ULN or creatinine clearance rate (CCr) ≥60ml/min, (Cockcroft-Gault formula);

You may not qualify if:

• 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;
• ≥ NCI CTCAE grade 2 peripheral neuropathy;
• Infection requiring antibiotics within 14 days before the start of the trial;
• Patients with bone metastases at risk of paraplegia;
• Patients with any severe and/uncontrolled disease, including:
• Patients with poor blood pressure control using antihypertensive drugs (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg); patients with grade II or higher myocardial ischemia or myocardial infarction, arrhythmia (including QT interval ≥480ms); patients with III-IV heart failure according to NYHA criteria or cardiac ultrasound examination suggesting left ventricular ejection fraction (LVEF) \<50%;

Sponsors & Collaborators

• Peking University: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

anlotinib; Albumin-Bound Paclitaxel; Taxes; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations

Study Officials

• Lin Shen, MD, PhD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lin Shen

CONTACT

0086-010-88196340; Doctorshenlin@sina.com

Yakun Wang

CONTACT

0086-010-88196340; wykun1991@126.com

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: January 16, 2024
• First Posted: January 25, 2024
• Study Start: February 25, 2024
• Primary Completion: August 25, 2025
• Study Completion (Estimated): August 25, 2026
• Last Updated: January 25, 2024

Record last verified: 2024-01

Locations

CN (1)