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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Early Phase 1

Conditions: Lung Cancer Metastatic; EGFR Gene Mutation; Lung Cancer

Treatments: Drug: Osimertinib; Drug: Dacomitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT03755102

18-341

Details and patient eligibility

About

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

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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17 participants in 2 patient groups

Cohort 1: Participants treated with dacomitinib alone

Experimental group

Description:

Participants in this cohort have a somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy.

Treatment:

Drug: Dacomitinib

Cohort 2: Participants treated with dacomitinib in combination with osimertinib

Experimental group

Description:

Participants in this cohort have a secondary acquired EGFR mutation in addition to the sensitizing mutation

Treatment:

Drug: Dacomitinib

Drug: Osimertinib