Safety and Efficacy of Genolimzumab (GB226) in Combination With Fruquintinib

NCT03976856 | Unknown Phase 1

• 1 other identifier: Gxplore-015
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a multi-center, open-label, dose-finding phase Ib clinical study with extension phase, which is aimed at evaluating the efficacy and safety of GB226 combined with fruquintinib in treatment of relapsed or metastatic NSCLC patients with EGFR-sensitive mutations who have failed to respond to EGFR-TKI treatment,evaluating the pharmacokinetic characteristics of GB226 and fruquintinib, and the immunogenicity of GB226, and preliminarily evaluating the antitumor activity of GB226 and fruquintinib.

Conditions

Metastatic Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• Incidence of Adverse Event

  Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03

  all adverse events will be recorded from the time the consent form is signed through 90 days following cessation of treatment.

• Incidence of Serious Adverse Event

  Assessment of serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03

  all adverse events will be recorded from the time the consent form is signed through 90 days following cessation of treatment.

• Dose Limited Toxicity

  Incidence of Dose Limited Toxicity

  Day 1 to Day 28 after first dose

• Maximum Tolerated Dose

  Defined as the highest dose tested in which only 0 or 1 out of 6 evaluable patients experience a dose limiting toxicity, as graded by the National Cancer Institute (NCI) Common terminology Criteria for Adverse Events (CTCAE) version 4.03

  Day 1 to Day 28 after first dose

Secondary Outcomes (17)

• Cmax

  up to 90 days after the last administration

• Tmax

  up to 90 days after the last administration

• AUC0-t

  up to 90 days after the last administration

• AUC0-∞

  up to 90 days after the last administration

• MRT

  up to 90 days after the last administration

Study Arms (1)

GB226+Fruquintinib

EXPERIMENTAL

Geptanolimab combined with Fruquintinib

Drug: GB226; Drug: Fruquintinib

Interventions

GB226 DRUG

Geptanolimab, 210mg，q2w，ivgtt.

Also known as: Geptanolimab

GB226+Fruquintinib

Fruquintinib DRUG

Fruquintinib, 3mg or 4mg or 5mg, qd.po. 3 weeks-on,1 week-off

Also known as: HMPL-013

GB226+Fruquintinib

Eligibility Criteria

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

You may qualify if:

• Aged 18-75 years, male or female;
• Understanding the procedures and contents of the study, and voluntarily signing the written informed consent form;
• Histologically or cytology confirmed relapsed or metastatic NSCLC;
• EGFR gene sensitive mutation is confirmed positive, any of following is met: exon 19 deletion (19DEL), exon 21 point mutation (L858R / L861Q), 18 exon point mutation (G719X), 20 exon point mutation (S768I). Moreover, the following conditions are met:
• No T790M mutation after failure of EGFR-TKI treatment;
• T790M mutation after EGFR-TKI treatment failure, and failed to respond to third-generation EGFR-TKI treatment; primary T790M mutation, progressed after third-generation EGFR-TKI treatment or no other available effective therapies;
• The above patients failed to respond to chemotherapy or are unwilling to or intolerable to chemotherapy;
• According to the RECIST 1.1 criteria, at least one target lesion (the lesion with a longest diameter ≥10 mm, or a lymph node with a short diameter ≥15 mm) are measured by CT or MRI;
• Expected survival ≥ 3 months;
• ECOG score: 0-1;
• Completion of systemic chemotherapy, radical/extensive therapy, or previous anti-tumor biological therapies (tumor vaccine, cytokine or growth factor for the purpose of tumor control) for at least 4 weeks, completion of local palliative radiotherapy for at least 1 week;
• The EGFR-TKI treatment has ended over 2 weeks before the use of study drugs;
• Patients who have not previously received treatment with TKI or monoclonal antibodies against Vascular Endothelial Growth Factor (VEGF) and/or VEGFR;
• At least 8 weeks after completion of major surgery requiring general anesthesia before the use of study drugs; at least 4 weeks after completion of surgery requiring local anesthesia/epidural anesthesia and recovery from the surgery;
• Discontinuation of systemic corticosteroids for at least 2 weeks before the use of study drugs (prednisone \> 10 mg/day or equivalent dose);

You may not qualify if:

• Patients with lung squamous cell carcinoma (including adenosquamous carcinoma);
• ALK fusion gene rearrangement confirmed by genetic testing;
• Patients with history of other malignant tumors (except cured cervical carcinoma in situ, basal cell carcinoma of skin or squamous cell carcinoma) may not participate in the study unless the diseases have been cured for at least 5 years prior to enrollment, and it is estimated that no other treatment will be required throughout the study;
• Detection of the tumor lesion ≤ 5 mm from the large vessel, or a central tumor that invaded the local large vessel; or a significant pulmonary cavity or necrotizing tumor by imaging (CT or MRI);
• Active central nervous system (CNS) metastasis, including symptomatic brain metastasis, meningeal metastasis or spinal cord compression; patients with asymptomatic brain metastases can be enrolled (no progression and/or neurological symptoms or signs after surgical resection within at least 4 weeks after radiotherapy, no history of treatment with glucocorticoids, anticonvulsants or mannitol);
• Symptomatic, uncontrollable serous effusions such as ascites, pleural effusion, or pericardial effusion;
• History of arterial thrombosis or deep vein thrombosis within 6 months prior to enrollment, evidence or history of bleeding tendency within 2 months prior to enrollment, regardless of severity;
• Patients with thrombolytic therapy or therapeutic anticoagulant drugs (except prophylactic anticoagulant drugs) within 10 days before the first study drug;
• History of active, known autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, except type I diabetes, hypothyroidism that can be controlled by hormone replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo and psoriasis) and controlled celiac disease.
• Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies (or any other antibodies that act on T-cell costimulatory or checkpoint pathways);
• Uncontrolled hypertension (systolic blood pressure﹥140mmHg and/or diastolic blood pressure﹥90mmHg), pulmonary hypertension or unstable angina; myocardial infarction, bypass surgery or stent surgery within 6 months before administration of drug; history of chronic heart failure that meets the criteria for grade 3-4 defined by New York Heart Association (NYHA); severe arrhythmia requiring treatment, including QTc interval ≥450ms for male subjects and ≥ 470ms for female subjects (calculated by Fridericia formula); left ventricular ejection fraction (LVEF) \<50%; cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 6 months before administration of drug;
• Skin wounds, surgical site, wound site, severe mucosal ulcers or fractures that are not completely healed;
• Dysphagia or gastrointestinal disorders that may significantly affect absorption of oral drugs or any conditions that may cause gastrointestinal bleeding or perforation at the discretion of the investigator (such as duodenal ulcer, gastrointestinal obstruction, diverticulitis, intraperitoneal abscess, metastasis of peritoneal carcinoma, acute Crohn's disease, ulcerative colitis, large area stomach and small bowel resection). Patients with chronic Crohn's disease and ulcerative colitis (except total colon and rectal resection) should be excluded even during inactivity period. Patients with hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis syndrome; patients with history of intestinal perforation and intestinal fistula who are not recovered after surgery;
• Previouly or currently suffered from active tuberculosis infection, or other infections requiring systemic treatment;
• Positive human immunodeficiency virus antibody (HIV-Ab), treponema pallidum antibody (TP-Ab) or hepatitis C antibody (HCV-Ab); positive hepatitis B virus surface antigen (HBsAg), and hepatitis B virus DNA copy number \> upper limit of normal of the testing institution;

Sponsors & Collaborators

• Genor Biopharma Co., Ltd.: lead
• Hutchison Medipharma Limited: collaborator

Study Sites (1)

Shanghai chest hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

HMPL-013

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Shun Lu, Doctor

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shawn Yu, Master

CONTACT

86-010-65260820; shawn.yu@genorbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: June 6, 2019
• Study Start: July 23, 2019
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: March 3, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)