The Efficacy and Safety of LMV-12 Combined With Osimertinib in NSCLC

NCT06109558 | Recruiting Phase 1

• 1 other identifier: 2023049
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, dose-escalation, multicenter phase I/II clinical trial. The primary endpoints of this study were to evaluated the safety, tolerability, pharmacokinetic profile and preliminary efficacy of HE003 in combination with osimertinib in patients with advanced solid tumors who have failed previous standard therapy. The secondary endpoints of this study were to evaluated the efficacy HE003 in combination with osimertinib in patients with advanced solid tumors who have failed previous standard therapy.

Conditions

Non Small Cell Lung Cancer; RET Gene Mutation; MET Amplification; EGF-R Positive Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• ORR

  Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects

  Time from first subject dose to study completion, or up to 36 month

• Adverse event and safety

  Number of participants experiencing clinical and laboratory adverse events (AEs)

  Time from first subject dose to study completion, or up to 36 month

Secondary Outcomes (2)

• PFS

  Time from first subject dose to study completion, or up to 36 month

• OS

  Time from first subject dose to study completion, or up to 36 month

Study Arms (2)

Cohort A

EXPERIMENTAL

Patients with MET amplication（by FISH, NGS or IHC）

Drug: LMV-12(HE003)

Cohort B

EXPERIMENTAL

Patients with RET fusion.

Drug: LMV-12(HE003)

Interventions

LMV-12(HE003) DRUG

1 cycle was 28 days. LMV-12(HE003), 30mg or 60mg, continuously for 21 days, and the drug was discontinued for 7 days. Osimertinib, 80mg, continuously for 28 days.

Also known as: Osimertinib

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• Eligible subjects selected for this study must meet all of the following criteria:
• Sign written informed consent before implementing any trial-related procedures;
• Age ≥18 years old;
• No limit on the gender;
• Histological or cytological confirmed advanced or metastatic non-small cell lung cancer, ineligible for radical surgery, relapse after failure of previous treatment with first-line (including first, second, and third generation)EGFR inhibitors.
• Cohort A：MET amplification,(by FISH, NGS or IHC) Cohort B：RET fusion.
• Laboratory tests for organ function levels must meet the following requirements:
• Absolute neutrophil count ≥ 1.5 × 109/L;
• Platelet count ≥ 100 × 109/L;
• Hemoglobin ≥ 9 g/dL;
• Bilirubin ≤1.5 times ULN; e) AST and ALT ≤2.5 times ULN (total bilirubin ≤3 times the upper limit of normal and AST and ALT ≤5 times the upper limit of normal are permitted if hepatic metastases are present);
• f) Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min (according to the Cockcroft-Gault formula);
• For premenopausal women of childbearing potential a pregnancy test must be performed within 7 days prior to initiation of treatment, a serum pregnancy test must be negative, and they must be non-lactating; all enrolled patients (whether male or female) should use adequate barrier contraception throughout the treatment period and for 3 months after completion of treatment.

You may not qualify if:

• Subjects treated with CYP isozyme inducers or inhibitors (see Appendix 4 for details) within 3 weeks prior to enrollment;
• Pregnant or lactating women;
• History of immunodeficiency or other acquired, congenital immunodeficiency diseases;
• Patients with prior bone marrow transplantation or prior solid organ transplantation;
• Patients with a combination of gastrointestinal perforation, gastrointestinal fistula, or non-gastrointestinal fistula;
• Prior history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease.
• Hepatitis B, hepatitis C, or human immunodeficiency virus (HIV-positive). Hepatitis B is eligible for this study at \<500 IU/mL (or 2500 cps/mL) by quantitative HBV-DNA testing, and hepatitis C (HCV) antibody-positive patients are eligible for this study only if the polymerase chain reaction shows HCV RNA negativity;
• Fulfillment of any of the following cardiac criteria: (i) Bazetts' mean corrected QT interval (QTc) derived from electrocardiogram (ECG) examination at rest \>470 msec (women) or \>450 msec (men) (in the case of the 1st abnormality, retested once within 48 h and calculated by averaging the results of the 2 times); and (ii) a wide variety of clinically significant rhythmic, conduction, and resting ECG morphologic Abnormalities, such as complete left bundle branch block, grade III conduction block, grade II conduction block, PR interval \>250 msec; (iii) Myocardial ischemia or myocardial infarction of grade I or higher, or congestive heart failure of grade ≥2 (New York Heart Association (NYHA) classification); (iv) Factors that may increase the risk of prolongation of QTc or the risk of arrhythmic events, such as coronary artery disease, heart failure hypokalemia, congenital long QT syndrome, family history of a first-degree relative with long QT syndrome or sudden unexplained death before the age of 40, and ongoing use of any medication known to prolong the QT interval;

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

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

• Nong Yang, MD

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongchang C Zhang, MD

CONTACT

+8613873123436; zhangyongchang@csu.edu.cn

Nong C Yang, MD

CONTACT

+8613873123436; yangnong0217@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director of Clinical Trial

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: October 31, 2023
• Study Start: December 31, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): July 30, 2027
• Last Updated: May 30, 2024

Record last verified: 2024-05

Locations

CN (1)