A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.

A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progressionon Osimertinib.

The purpose of this study is to assess whether dacomitinib after osimertinib is effective in participants with metastatic EGR-mutant lung cancers.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Lung Cancer Metastatic; EGFR Gene Mutation
• Intervention / Treatment: Drug: Dacomitinib; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Rockville Centre
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent
• Advanced biopsy-proven metastatic non-small cell lung cancer
• Somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy
• Prior treatment with osimertinib with response followed by disease progression
• No prior first or second generation EGFR inhibitor treatment (gefitinib, afatinib, erlotinib)
• Archival tissue available from a tumor biopsy done after disease progression on osimertinib or willing to undergo a tumor biopsy or liquid biopsy after disease progression on osimertinib 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

• 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/mm3
  • Hemoglobin>/=8.0 g/dL
  • Platelets >/=75,000/mm3

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
• Continue to have unresolved > grade 1 toxicity from any previous treatment Treatment
• Patients with a known mechanism of resistance to osimertinib that will clearly not respond to dacomitinib therapy (i.e. known MET amplification, ALK fusion, RET fusion).
• Symptomatic brain metastases or leptomeningeal disease requiring escalating doses of steroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Participants treated with dacomitinib alone; Participants in this cohort have a somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy.	Drug: Dacomitinib; Cohort 1 Dacomitinib Dosing: Dose level 1: Dacomitinib 45mg daily Dose level -1: Dacomitinib 30mg daily Dose level -2: Dacomitinib 15mg daily Cohort 2 Dacomitinib Dosing: Dose level 1: Dacomitinib 30 mg daily Dose level -1: Dacomitinib 15 mg daily
Experimental: Cohort 2: Participants treated with dacomitinib in combination with osimertinib; Participants in this cohort have a secondary acquired EGFR mutation in addition to the sensitizing mutation	Drug: Dacomitinib; Cohort 1 Dacomitinib Dosing: Dose level 1: Dacomitinib 45mg daily Dose level -1: Dacomitinib 30mg daily Dose level -2: Dacomitinib 15mg daily Cohort 2 Dacomitinib Dosing: Dose level 1: Dacomitinib 30 mg daily Dose level -1: Dacomitinib 15 mg daily; Drug: Osimertinib; In cohort 2, participants will begin on dacomitinib orally daily in combination with Osimertinib Dose level Osimertinib Dosing: Dose level 1: Osimertinib 80 mg daily Dose level -1: Osimertinib 40 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	1 year
Progression-free survival	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Helen Yu, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2018
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (Actual): November 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Memorial Sloan Kettering Cancer Center; osimertinib; dacomitinib; EGFR C797S; EGFR mutant lung cancer; 18-341
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: 18-341

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No