Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Trastuzumab

Antibodies

Antibodies, Monoclonal

Osimertinib

Immunoglobulins

Mitogens

Trastuzumab biosimilar HLX02

Necitumumab

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive necitumumab IV over 60 minutes and trastuzumab IV over 30-90 minutes on days 1 and 15. Patients also receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Quality-of-Life Assessment

Questionnaire Administration

Karla Russell

Jonathan W. Goldman

Jonathan W Goldman

This phase Ib/II trial studies the side effects and best dose of trastuzumab and necitumumab together with osimertinib, and to see how well they work for the treatment of stage IV non-small cell lung cancer that is EGFR-mutated, resistant to osimertinib, and has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as trastuzumab and necitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving trastuzumab and necitumumab together with osimertinib may work better than osimertinib alone in treating patients with stage IV EGFR-mutated non-small cell lung cancer.

PRIMARY OBJECTIVES:

I. Determine the recommended phase II dose (RP2D) of osimertinib and necitumumab in combination with trastuzumab. (Phase Ib) II. Evaluate the efficacy of osimertinib, necitumumab, and trastuzumab (ONT) as measured by objective response rate (ORR), which is defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of ONT as measured progression free survival (PFS), duration of response (DoR), and overall survival (OS).

II. To evaluate the safety and tolerability of ONT as measured by adverse events (AEs) defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V 5.0).

EXPLORATORY OBJECTIVES:

I. To assess patient-reported outcomes on health-related quality of life and adverse events.

II. Assess potential biomarkers associated with response from liquid biopsies and optional but recommended baseline tissue biopsy.

IIa. Correlate pre-and post-treatment biopsies molecular changes with response. III. Correlate mutant allele fraction in circulating tumor deoxyribonucleic acid (DNA) (ctDNA) via liquid biopsy with response.

OUTLINE: This is a phase Ib, dose-escalation study of osimertinib and necitumumab followed by a phase II study.

Patients receive necitumumab intravenously (IV) over 60 minutes and trastuzumab IV over 30-90 minutes on days 1 and 15. Patients also receive osimertinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed up at 30 days, every 8 weeks through week 24, then every 12 weeks up to 1 year.

Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer

UCLA L-08: A Phase Ib/II Study of Combined HER Inhibition Adding Necitumumab and Trastuzumab to Osimertinib in Patients With Refractory EGFR-Mutated Lung Cancer

Will be obtained from the Functional Assessment of Cancer Therapy - Lung (FACT-L) questionnaire. Will be analyzed by the clinical biostatisticians in the University of California, Los Angeles (UCLA) Department of Medicine Medical Statistics Core.

Will be assessed using response from liquid biopsies and optional but recommended baseline tissue biopsy. Will correlate pre-and post-treatment biopsies molecular changes (i.e. expression of HER2, HER3, AXL, MET) with response.

Will be assessed using liquid biopsy with response.

Will be defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0).

Will be based on the Full Analysis Set (FAS) of the phase II portion of the trial and the phase Ib patients treated at the recommended phase II dose (RP2D). ORR is defined as defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be determined by the investigator. A Cox proportional hazards model will be used to estimate the hazard ratio and its 95% confidence interval (CI).

PFS is defined as the time from trial initiation to cancer progression per RECIST 1.1 based on investigator assessment or death due to any cause.

DoR is time from documentation of tumor response to disease progression.

OS is defined as time from randomization to death by any cause.

Will be assessed using Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer	NCT04285671	Metastatic Lung... Refractory Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Necitumumab Osimertinib Quality-of-Life... Questionnaire A... Trastuzumab	18 Years -	Jonsson Comprehensive Cancer Center
Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer	NCT04285671	Metastatic Lung... Refractory Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Necitumumab Osimertinib Quality-of-Life... Questionnaire A... Trastuzumab	18 Years -	Jonsson Comprehensive Cancer Center

Spots Global Cancer Trial Database for stage iv lung cancer american joint committee on cancer (ajcc) v8