Osimertinib, Cetuximab, and Tucatinib for the Treatment of EGFR-Mutant Stage IV or Recurrent Non-small Lung Cell Cancer

NCT06067776 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UCDCC#298NCI-2022-04431P30CA093373
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of osimertinib, cetuximab, and tucatinib in treating patients with EFGR-mutant non-small cell lung cancer that is stage IV or has come back (recurrent). Osimertinib and tucatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cetuximab is a chimeric human/mouse IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR), a receptor overexpressed in many types of cancer, and may interfere with the ability of tumor cells to grow and spread. Giving osimertinib, cetuximab, and tucatinib may work better in treating patients with non-small cell lung cancer.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  The occurrence of a dose-limiting toxicity in participants receiving the combination of osimertinib, cetuximab, and tucatinib.

  First dose through cycle 1 (each cycle is 28 days)

Secondary Outcomes (3)

• Incidence of adverse events

  First dose through 30 days post last dose

• Objective response rate (ORR)

  First dose through progression or end of study treatment, whichever occurs first, assessed up to 10 months

• Progression-free survival (PFS)

  Up to 2 years post last dose

Study Arms (1)

Treatment (tucatinib, osimertinib, cetuximab)

EXPERIMENTAL

Patients receive tucatinib 200mg orally BID, osimertinib 80mg orally daily, and cetuximab 250mg/m\^2 IV every 2 weeks of a 28-day cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Cetuximab; Drug: Osimertinib; Drug: Tucatinib

Interventions

Cetuximab BIOLOGICAL

Given IV

Also known as: ERBITUX

Treatment (tucatinib, osimertinib, cetuximab)

Osimertinib DRUG

Given PO

Also known as: TAGRISSO

Treatment (tucatinib, osimertinib, cetuximab)

Tucatinib DRUG

Given PO

Also known as: TUKYSA

Treatment (tucatinib, osimertinib, cetuximab)

Eligibility Criteria

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

You may qualify if:

• Participants with Stage IV or recurrent/metastatic histologically confirmed non-small cell lung cancer (NSCLC).
• NSCLC must harbor at least one of the following EGFR activating mutations: Exon 21 L858R, Exon 19 deletion, Exon 18 G719X, Exon 21 L861Q, Exon 20 S768I.
• For patients in the dose escalation cohort, patients must have progressed on any prior EGFR-Tyrosine Kinase Inhibitor (TKI) and if T790M positive must have also progressed on osimertinib. Participants in the dose expansion cohort must have had progressive disease as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version (v)1.1 criteria on osimertinib as first-line therapy.
• \. Participants in the dose expansion cohort must be negative for clinically significant non-ERBB bypass tract resistance such as MET amplification, BRAF mutation, RAS-RAF-MAPK alteration, ALK fusion, RET fusion by a Clinical Laboratory Improvement Amendments (CLIA) (performed after progression on prior EGFR-TKI; if any questions please consult with the Principal Investigator). A defined subset of patients in the expansion cohort will have human epidermal growth factor receptor (HER2) aberrant signaling as putative resistance to osimertinib with overexpression/amplification (or more rarely HER2 Exon 20 insertion mutation) as determined by IHC (3+ IHC) or FISH (HER2/CEP17 \> 2.2 or HER2 copy number \> 6) or NGS for HER2 mutation.
• Adequate archival tissue from a biopsy performed after progression of disease on previous osimertinib (or last EGFR-TKI for dose escalation cohort) or willingness to consent for a fresh tumor biopsy.
• Participants must have measurable disease by RECIST 1.1, by positron emission tomography/computed tomography (PET/CT) or CT imaging within 28 days prior to registration. The CT from a combined PET/CT may be used only if it is of diagnostic quality.
• Men and women \>=18 years of age at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Life expectancy greater than 3 months.
• Absolute neutrophil count \>= 1.5 x 10\^9/L.
• Platelets \>= 100 x 10\^9/L.
• Hemoglobin \>= 9 g/dL.
• Serum albumin \>= 2.5 g/dL.
• Bilirubin =\< 1.5 x the upper limit of normal (ULN).
• Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate transaminase (AST) =\< 2.5 x ULN.

You may not qualify if:

• History of pneumonitis requiring steroids, including history of radiation-induced pneumonitis.
• Known or suspected leptomeningeal disease as documented by the investigator. Stable asymptomatic brain metastases not requiring steroids is allowed; radiation for brain metastases is allowed as long as there is a two-week washout period prior to starting study treatment.
• Have poorly controlled (\> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding central nervous system (CNS)-directed therapy.
• The participant has a known allergy / history of hypersensitivity reaction to any of the treatment components (including any ingredient or similar ingredient used in the product formulations) or red meat.
• History of tick bite or any other contraindication to one of the administered treatments.
• History of arterial or venous thromboembolism within 3 months prior to study enrollment. Participants with a history of venous thromboembolism beyond 3 months prior to study enrollment can be enrolled if they are appropriately treated with low molecular weight heparin or direct oral anti-coagulants.
• History or evidence of current clinically relevant coronary artery disease \>= Grade III by the Canadian Cardiovascular Society Angina Grading Scale or uncontrolled congestive heart failure of current \> Class III as defined by the New York Heart Association.
• The participant has experienced myocardial infarction within 6 months prior to study enrollment.
• The participant has a history of clinically significant ventricular arrhythmia, cardiac arrest, or torsades de pointes.
• The participant has high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency.
• The participant has uncontrolled or poorly controlled hypertension (\>180 mmHg systolic or \> 130 mmHg diastolic.
• Use of a strong cytochrome P450 CYP2C8 inhibitor within 5 half-lives of the inhibitor or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to the first dose of study treatment.
• The participant is pregnant or breast feeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment.
• The participant has any ongoing or active clinically significant infection, including known active tuberculosis or known ongoing or active infection with the human immunodeficiency virus.
• Recent (within 30 days before enrollment) or concurrent yellow fever vaccination.

Sponsors & Collaborators

• Jonathan Riess: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Cetuximab; osimertinib; tucatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jonathan W Riess

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Selina Laqui

CONTACT

916-734-0565; sblaqui@ucdavis.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 17, 2023
• First Posted: October 5, 2023
• Study Start: January 1, 2024
• Primary Completion: January 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: October 5, 2023

Record last verified: 2023-10

Locations

US (1)