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

Phase 1

Active, not recruiting

• Conditions: Metastatic Non-small Cell Lung Cancer
• Interventions: Drug: Dacomitinib; Drug: Osimertinib

• Registration Number: NCT03810807
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-17
• Study First Submitted: 2019-01-17
• Study First Submitted QC: 2019-01-17
• Study First Posted: 2019-01-22
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-04
• Primary Completion: 2026-01
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 22

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dacomitinib and Osimertinib	Dacomitinib	Patients will begin on combination dacomitinib and osimertinib at the prescribed doses. A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.
Dacomitinib and Osimertinib	Osimertinib	Patients will begin on combination dacomitinib and osimertinib at the prescribed doses. A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.

Primary Outcome Measures

Name	Time	Method
Best overall response rate	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
maximum tolerated dose	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.

Trial Locations

Locations (7)

Memorial Sloan Kettering Westchester; 🇺🇸 Harrison, New York, United States

Memorial Sloan Kettering Bergen; 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Basking Ridge; 🇺🇸 Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth; 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Nassau; 🇺🇸 Uniondale, New York, United States

Memorial Sloan Kettering Commack; 🇺🇸 Commack, New York, United States