To Evaluate the Efficacy of QLH11811 in Advanced NSCLC Patients With EGFR Mutation

NCT05555212 | Unknown Phase 1

• 1 other identifier: QLH11811
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open-label, dose escalation and cohort expansion study and conducted in China and the United States to investigate the safety, tolerability and preliminary efficacy of QLH11811 in advanced or metastatic NSCLC patients who have progressed after prior EGFR-TKI treatment. The study consists of the following 2 phases: phase 1: dose escalation (1a) and phase 2: cohort expansion (1b).

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Safety parameters

  adverse events (AEs), serious adverse events (SAEs) and other safety results

  2 years

• ORR

  Objective response rate (ORR) (evaluated by the Independent Review Committee in NSCLC patients who have EGFR-C797S mutation according to RECIST v1.1).

  2 years

Secondary Outcomes (1)

• Possible metabolites of QLH11811 in plasma

  6 month

Study Arms (1)

dose escalation (in China)

EXPERIMENTAL

Drug: QLH11811

Interventions

QLH11811 DRUG

In Ia phase, subjects will first receive oral single dose of QLH11811, then will be observed for 7 days. If the drug is tolerated by the subjects, the subjects will continue to receive the oral repeat dose of QLH11811 for 21 consecutive days. Upon the completion of observation for DLT in the subjects (DLT observation period is the 28 days after the first dose), the subjects will continue to receive the repeat dose of QLH11811 in Cycle 2 and subsequent cycles. The dosing frequency in Cycle 2 and subsequent cycles is once daily, and each cycle has 3 weeks. The RP2D of QLH11811 is determined on the basis of comprehensive evaluation of all safety and tolerability data and all available PK, PD and efficacy data during the dose escalation phase. In phase 1b, the cohort expansion study is carried out for all cohorts in China and the United States concurrently according to the determined RP2D.

dose escalation (in China)

Eligibility Criteria

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

You may qualify if:

• Patients who participate voluntarily, sign informed consent form (ICF), and will be able to follow the study procedures;
• Aged ≥ 18 years;
• Patients who are histologically or cytologically diagnosed with EGFR mutation and have unresectable locally advanced or recurrent/metastatic NSCLC;
• EGFR mutation requirements:
• Dose escalation phase (phase 1a): NSCLC patients who have progressed after standard EGFR-TKI treatment or cannot tolerate standard of care;
• Cohort expansion phase (phase 1b):
• Cohort 1: advanced NSCLC patients who have progressed after treatment with third-generation EGFR-TKIs and have EGFR C797S mutation.
• Cohort 2: advanced NSCLC patients who have progressed after standard EGFR-TKI treatment but have no other additional driver gene mutation(s).
• Cohort 3: advanced NSCLC patients who have progressed after EGFR-TKI treatment and have T790M mutation.
• Cohort 4: patients with locally progressed, unresectable or recurrent metastatic NSCLC who are naive to EGFR-TKI treatment and have 19del or 21L858R mutation among EGFR sensitive mutations.
• Patients who agree to provide tumor samples (fresh tissues or archived samples) for analysis of EGFR gene.
• Dose escalation phase: tumor samples collected from the progression site of disease during or after PD after the last TKI treatment should be provided for new genetic testing The subjects who fail to provide tumor samples will be allowed to enroll only after communication and consultation with the sponsor.
• Cohort expansion phase:
• Cohort1: tumor samples collected from the progression site of disease during or after PD after the last TKI treatment should be provided for genetic testing at central laboratory.
• Cohorts 2 and 3: tumor samples collected from the progression site of disease during or after PD after the last TKI treatment should be provided for genetic testing. The genetic testing will be exempted if subjects have the test results meeting the above requirements before their enrollment.

You may not qualify if:

• Patients who have received systemic anticancer therapies (e.g., chemotherapy, molecularly targeted therapy, radiotherapy, biotherapy, hormone therapy, vaccine therapy), or antineoplastic TCM therapy in the 2 weeks prior to the first dose of study treatment; or who have received immune-checkpoint inhibitor therapy in the 4 weeks prior to the first dose of study treatment;
• Patients who have received radical radiotherapy (including radiotherapy of more than 25% of bone marrow) in the 4 weeks prior to the first dose, or who have received local palliative radiotherapy for bone metastatic lesions in the 1 week prior to the first dose;
• Patients who have received strong or moderate CYP3A, P-gp inhibitors in the 1 week prior to the first dose or in 5 half-lives of these drugs (whichever is longer), or need to continue to receive these drugs during the study; and who have received strong or moderate CYP2B6, CYP1A2 and CYP3A inducers in the 4 weeks prior to the first dose;
• Patients who are in the treatment period of other interventional clinical studies in the 4 weeks prior to the first dose. However, participants of non-interventional clinical studies (e.g., epidemiologic studies) are eligible for enrollment in this study. Patients in the survival follow-up period of interventional clinical studies are also eligible for enrollment in this study;
• Patients who have active bacterial, fungal or viral infection requiring systemic therapies within the 1 week prior to the first dose;
• Patients who have underwent a major operation (e.g., a surgical operation requiring local or general anesthesia and hospitalization) in the 3 weeks prior to the start of study treatment;
• Patients with a history of chronic diarrhea, including but not limited to Crohn's disease, irritable bowel syndrome, etc.;
• Patients who have experienced \> CTCAE Grade 1 continuous diarrhea within the 1 week prior to the first dose;
• Patients with serious respiratory disorders, e.g. interstitial lung disease, radiation pneumonitis, drug-induced pneumonia (however, patients whose conditions have resolved and stabilized for 3 months or more are eligible for enrollment);
• Patients with symptomatic metastasis to central nervous system (CNS) and/or with meningitis carcinomatosa.
• Note: patients with brain metastases whose clinical symptoms have stabilized after treatment are eligible for participation in the study, provided that their conditions are radiographically stabilized (defined as stability demonstrated by 2 brain images acquired by the same imaging technique after treatment of brain metastases). These imaging scans should be carried out at an interval of at least 4 weeks, and show no signs of intracranial progression. Furthermore, brain metastases or its treatment induced neurologic symptoms need to regress to baseline level or resolve. All steroids administered as a part of the treatment must be completed ≥ 3 days prior to the administration of study treatment.
• Patients with clinically significant cardiovascular and cerebrovascular diseases, including but not limited to:
• Myocardial infarction or unstable angina in the 6 months prior to the first dose;
• Stroke or transient ischemic attack in the 6 months prior to the first dose;
• Any clinically significant abnormalities in resting ECG in terms of cardiac rhythm, heart rate, conduction or morphology, e.g. complete left bundle branch block, third-degree conduction block, second-degree conduction block, PR interval \> 250 ms, etc.;

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Qilu Pharmaceutical.Co.,Ltd

Jinan, Shandong, 273200, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Study Design

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

Model Details: This is a phase 1, open-label, dose escalation and cohort expansion study and conducted in China and the United States to investigate the safety, tolerability and preliminary efficacy of QLH11811 in advanced or metastatic NSCLC patients who have progressed after prior EGFR-TKI treatment. The study consists of the following 2 phases: phase 1: dose escalation (1a) and phase 2: cohort expansion (1b), as detailed in Overall Schematic of Study Design. Phase 1a: this dose escalation study will be conducted in China and the United States, respectively, and the dose escalation will start from starting dose in China and from dose level next to the MTD determined in Chinese subjects in the United States. Phase 1b: after the determination of RP2D, this cohort expansion study will be conducted in China and the United States concurrently to observe the safety, tolerability and efficacy of QLH11811 in advanced NSCLC patients who have EGFR mutation

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: September 26, 2022
• Study Start: October 25, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: March 28, 2023

Record last verified: 2022-09

Locations

CN (1)