A Study of Gentuximab in Combination With Almonertinib in EGFR Mutation-positive Metastatic NSCLC

NCT05223595 | Unknown Phase 1

• 1 other identifier: Gensci043-Ib-LC
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multicenter, open label study to investigate the safety and efficacy of Gentuximab plus Almonertinib in metastatic NSCLC patients with EGFR mutation-positive.

Conditions

Metastatic Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities (DLT)

  Number of participants with one or more drug-related adverse events (AEs) defined as DLT in the protocol

  Up to 4 Weeks

• AEs or SAEs

  Drug-related adverse events (AEs) or any serious adverse events (SAEs)

  Baseline through study completion, about 2 years

Secondary Outcomes (6)

• Cmax

  Cycle 1(day1-day 15)& Cycle 2(day 1-day15) & Cycle 3(day 1) & Cycle 4(day 1) (28 days for every cycle)

• AUC

  Cycle 1(day1-day 15)& Cycle 2(day 1-day15) & Cycle 3(day 1) & Cycle 4(day 1) (28 days for every cycle)

• Objective response rate（ORR）

  From date of first dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

• Progression-free survival (PFS)

  From date of first dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

• Disease control rate (DCR)

  From date of first dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

Study Arms (1)

dose escalation

EXPERIMENTAL

Gentuximab at a dose of 8 mg/kg or 12 mg/kg based on body weight + Almonertinib at a dose of 110mg for one 28-day cycle

Drug: Gentuximab

Interventions

Gentuximab DRUG

Gentuximab: 8mg/kg or 12mg/kg intravenous (IV) infusion administered on Day 1 and 15 of each cycle; Almonertinib: 110 mg orally once daily.

Also known as: Almonertinib

dose escalation

Eligibility Criteria

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

You may qualify if:

• The subject can understand the process and methods of the study, complete the study in accordance with the protocol and is willing to sign a written informed consent.
• Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 8th edition).
• Phase Ib dose escalation Cohort: Previous genetic tests confirmed EGFR-sensitive mutations, and received one or two generations of EGFR TKI treatment. After drug resistance, it was confirmed to be positive for EGFR T790M mutation by biopsy or free DNA test.
• Phase Ib expansion Cohort: Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation \[exon 19 deletion or exon 21 (L858R) substitution mutation\].
• At least one Measurable lesion.
• ECOG Performance status (PS) score, 0-1 level.
• Adequate hematologic function, as defined by: Absolute neutrophil count (ANC) ≥1.5×109/L; hemoglobin concentration ≥90g/L; and platelet count ≥80×109/L.
• Adequate hepatic function, as defined by: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (liver metastases patients or Gilbert's Syndrome (unconjugated hyperbilirubinemia) patients ALT ≤ 5 × ULN, AST ≤ 5 × ULN, TBIL ≤ 3 × ULN).
• Adequate renal function, as defined by: serum creatinine level≤ 1.5 × ULN, or creatinine clearance ≥ 50ml / min.
• hour urine protein quantitation is \<1g（24-hour urine protein quantitative test should be performed when urine protein ≥2+ is found during screening visit）.
• A life expectancy of ≥12 weeks.
• Aged between 18 and 75 years
• Subjects (male and female) who have fertility must agree to use reliable contraceptive methods during the trial and in 3 months after the last administration. Female subjects in childbearing age must be negative for blood pregnancy test prior to enrollment.

You may not qualify if:

• History of other malignancies, excluding full treated non-melanoma skin cancer, in-situ cancer.
• Brain metastases unless asymptomatic, stable for at least 4 weeks, and not requiring steroids for at least 2 weeks prior to start of study treatment.
• Subject with positive HCV-Ab, Anti-HIV or TP-Ab, or positive HBS-Ag with copies of HBV DNA \> ULN.
• Interstitial lung disease
• Evidence of major coagulopathy or other obvious bleeding tendency，which， in the Investigator's opinion, makes it undesirable for the patient to participate in the trial
• Any of the following major cardiovascular disease： myocardial infarction or received coronary artery bypass graft within 6 months before the start of the study treatment uncontrolled congestive heart failure unstable angina within 6 months before the start of the study treatment any clinically important abnormalities in rhythm （sustained ventricular tachycardia, second degree heart block and third degree heart block）
• Uncontrolled diabetes
• Uncontrolled hypertension (blood pressures: systolic≥140 mmHg and/or diastolic ≥90 mmHg)
• Uncontrolled third space effusion (pleural effusion and pericardial effusion need to be drained or increased rapidly after drained in three days) .
• Evidence of active tuberculosis
• Prior treatment with third generation EGFR-TKIs
• Previously administrated with anti-angiogenic drugs.
• Has received systematic anti-tumor therapy such as chemotherapy, targeted therapy, immunotherapy, endocrine therapy, etc. within 4 weeks or 5 half-lives of the drug (whichever is shorter) before the first dose of investigational drug.
• Has received any biologics that targeted the immune system, such as TNF antagonist, anakinra, rituximab, abatacept and tocilizumab, etc. within 4 weeks before the first dose of investigational drug.
• Has received Chinese medicine with anti-cancer indications or immunomodulatory drugs （including thymosin，interferon，interleukin，except for the use of treatment for leural effusion）within 2 weeks before the first dose of investigational drug.

Sponsors & Collaborators

• Changchun GeneScience Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aumolertinib

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

Yunpeng Jin, Doctor

CONTACT

+86-18801970689; jinyunpeng@gensci-china.com

Huagang Li

CONTACT

+86-18521091678; lihuagang@gensci-china.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: January 4, 2022
• First Posted: February 4, 2022
• Study Start: April 2, 2021
• Primary Completion: September 30, 2023
• Study Completion: January 30, 2024
• Last Updated: February 4, 2022

Record last verified: 2022-01

Locations

CN (1)