A Phase Ib Study to Evaluate the Safety and Efficacy of Osimertinib in Combination With Ipilimumab in Patients With EGFR Mutated Non-Small-Cell Lung Cancer Tumors
Overview
- Phase
- Phase 1
- Intervention
- Ipilimumab
- Conditions
- Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)
- Sponsor
- University of Utah
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Short and Long term tolerability of ipilimumab in combination with osimertinib: Adverse Events (AEs)
- Status
- Active, Not Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a prospective, open label, interventional trial beginning with a phase 1b safety run-in followed by an expansion cohort.
Detailed Description
The primary objective is to assess the short and long term tolerability of ipilimumab in combination with osimertinib. The secondary objective is to assess efficacy of osimertinib in combination with ipilimumab. Ipilimumab will be given for a total of four doses and osimertinib will be given until treatment discontinuation criteria is met. Ipilimumab at the assigned dose level every 3 weeks for four doses in combination with once daily osimertinib.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subject aged ≥ 18 years.
- •Histologically or cytologically confirmed metastatic, non-small cell lung cancer (NSCLC).
- •The presence of any sensitizing epidermal growth factor receptor (EGFR) tumor mutation.
- •Currently on a stable dose of osimertinib (40 mg or 80 mg daily) ≥ 28 days without clinical disease progression.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Adequate organ function as defined as:
- •Hematologic:
- •White blood cell count \> 2.0 k/microliter (uL)
- •Platelet count \> 100,000/mm3
- •Hemoglobin ≥ 9 g/dL
Exclusion Criteria
- •Prior EGFR targeted therapy.
- •Prior radiation therapy within 2 weeks prior to cycle one day one.
- •Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo-or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
- •Known history of:
- •Immune-mediated colitis, inflammatory bowel disease, or interstitial lung disease/pneumonitis.
- •Intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
- •Current use of immunosuppressive medication at the time of study enrollment, EXCEPT for the following permitted steroids:
- •Intranasal, inhaled, topical steroids, eye drops or local steroid injection (eg,intra-articular injection);
- •Systemic corticosteroids at physiologic doses ≤ 10mg/day of prednisone or equivalent;
- •Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication).
Arms & Interventions
Treatment: all patients
Patients entering trial should be on stable dose of osi for ≥4 weeks. Patients will self-administer osi by mouth regardless of food once daily. Doses should be taken at about the same time every day (±6hrs) and recorded on the patient dosing diary. Doses missed outside of the dosing window should not be made up but patients should be instructed to take their next dose at their regularly scheduled time. Ipi will be administered at the assigned dose level every 21 days (±3days) for a max of 4 doses. Ipi must be infused using a volumetric pump over 90min (±10min) through an IV line. Upon completion of the ipilimumab regimen, patients will continue osimertinib daily until disease progression, initiation of new anti-cancer therapy, or death by any cause.
Intervention: Ipilimumab
Treatment: all patients
Patients entering trial should be on stable dose of osi for ≥4 weeks. Patients will self-administer osi by mouth regardless of food once daily. Doses should be taken at about the same time every day (±6hrs) and recorded on the patient dosing diary. Doses missed outside of the dosing window should not be made up but patients should be instructed to take their next dose at their regularly scheduled time. Ipi will be administered at the assigned dose level every 21 days (±3days) for a max of 4 doses. Ipi must be infused using a volumetric pump over 90min (±10min) through an IV line. Upon completion of the ipilimumab regimen, patients will continue osimertinib daily until disease progression, initiation of new anti-cancer therapy, or death by any cause.
Intervention: Osimertinib
Outcomes
Primary Outcomes
Short and Long term tolerability of ipilimumab in combination with osimertinib: Adverse Events (AEs)
Time Frame: The safety elevation period will be from cycle one day one to cycle two day 21. First 4 cycles=21 days. Additional cycles are 28days.
Adverse Events (AEs) as characterized by type, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v5.0), timing, seriousness, and relationship to study treatment.
Secondary Outcomes
- Efficacy of osimertinib in combination with ipilimumab: Objective response rate (ORR)(Patients will remain on treatment until progression and then followed for survival for 5 years from the end of treatment visit.)
- Efficacy of osimertinib in combination with ipilimumab: Osimertinib progression free survival (oPFS)(PFS defined as the time between initiation of osimertinib and documented progression, death, or 5 yrs. from end of treatment)
- Efficacy of osimertinib in combination with ipilimumab: Ipilimumab progression free survival (iPFS)(iPFS defined as the time between the initiation of ipilimumab and documented progression, death, or 5 yrs from end of treatment)
- Efficacy of osimertinib in combination with ipilimumab: Overall survival(will be assessed as the time between trial initiation and death of any cause up to 5 yrs after end of treatment)
- Efficacy of osimertinib in combination with ipilimumab(will be assessed as the time between radiographic progression and the initiation of any alternative anti-cancer therapy up to 5 yrs. after end of treatment.)