Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer

The purpose of this study is to test the safety of dacomitinib and osimertinib, at increasing doses, to find out what effects, if any, this combination of drugs has on people with metastatic EGFR mutant lung cancer that has not been treated with an EGFR TKI.

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Key information

Conditions

Metastatic Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

19 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Memorial Sloan Kettering Basking Ridge, Basking Ridge, New Jersey, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Written informed consent
Advanced biopsy-proven metastatic non-small cell lung cancer
Somatic activating mutation in EGFR in a tumor biopsy
No prior EGFR inhibitor treatment (gefitinib, afatinib, erlotinib, dacomitinib, osimertinib) however, prior treatment with other chemotherapies are allowed
Archival tissue available from a pre-treatment tumor biopsy or willing to undergo a tumor biopsy prior to study initiation.
Measurable (RECIST 1.1) indicator lesion not previously irradiated
Karnofsky performance status (KPS) ≥ 70%
Age >18 years old
Ability to swallow oral medication
Agree to use effective methods of contraception from the time of screening until 3 months after treatment discontinuation (for males and females of child-bearing potential)
Adequate organ function

AST, ALT ≤ 3 x ULN
Total bilirubin ≤1.5x ULN
Creatinine ≤ 1.5x ULN OR calculated creatinine clearance ≥ 60ml/min
Absolute neutrophil count (ANC) ≥ 1000 cells/mm^3
Hemoglobin≥9.0 g/dL
Platelets ≥100,000/mm^3

Exclusion criteria

Pregnant or lactating women
Any radiotherapy within 1 week of starting treatment on protocol.
Any major surgery within 1 weeks of starting treatment on protocol.
Any evidence of active clinically significant interstitial lung disease
A mean QTc >470ms (Fridericia"s correction), clinically important arrhythmia, conduction or morphology of resting ECG (eg complete LBBB, 1st -3rd degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmia)
Cardiovascular disease or cerebrovascular disease, CVA or MI < 6 months prior to study enrollment, unstable angina, NYHA >Grade II CHF, or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment
History of pneumonitis or interstitial lung disease (ILD), drug induced ILD, radiation pneumonitits that required steroid treatment, and any evidence of clinically active ILD
Serious chronic GI conditions associated with diarrhea
Symptomatic, unstable brain metastases requiring escalating doses of steroids
Continue to have unresolved > CTCAE grade 1 toxicity from any previous treatment

Treatment and study plan

dacomitinib

Drug

Dose level 1 Dacomitinib, Dose level 2 Dacomitinib, Dose level 3 Dacomitinib. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.

Osimertinib

Drug

Dose level 1, 2 and 3 Osimertinib 40mg daily. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.

Primary outcomes

maximum tolerated dose

Time frame: 1 year

The MTD will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity (DLT). DLT is defined as any of the toxicity events described below that occurs within cycle 1 of treatment with the combination of dacomitinib and osimertinib.
Best overall response rate

Time frame: 1 year

Tumor response will be assessed using RECIST 1.1.The NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial. Dose-limiting toxicities (DLT"s) are defined as any of the following events occurring during the first cycle of treatment

Sponsors and collaborators

Lead sponsor

Memorial Sloan Kettering Cancer Center

Other

Registry information

Official study title

Phase 1 Study of Combination Dacomitinib and Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers

Important dates

Study start: 2019
Primary completion: 2025
Study completion: 2025
First posted: Jan 22, 2019
Registry last updated: Dec 23, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed