Clinical Trials /

PhIb Study Evaluating Safety and Efficacy of Combination Osimertinib and Ipilimumab in Patients w EGFR Mutated NSCLC

NCT04141644

Description:

This is a prospective, open label, interventional trial beginning with a phase 1b safety run-in followed by an expansion cohort.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PhIb Study Evaluating Safety and Efficacy of Combination Osimertinib and Ipilimumab in Patients w EGFR Mutated NSCLC
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: HCI124882
  • NCT ID: NCT04141644

Conditions

  • Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)

Interventions

DrugSynonymsArms
IpilimumabBMS-734016, MDX-010Treatment: all patients
OsimertinibTagrissoTreatment: all patients

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment: all patientsExperimentalPatients 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.
  • Ipilimumab
  • Osimertinib

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.

          -  Patient has measurable disease as defined by RECIST 1.1 as assessed by either CT or
             MRI at the time of starting osimertinib.

          -  Currently on a stable dose of osimertinib (40 mg or 80 mg daily) ≥ 28 days without
             clinical disease progression.

          -  ECOG Performance Status ≤ 2.

          -  Adequate organ function as defined as:

               -  Hematologic:

                    -  White blood cell count > 2.0 g/dL

                    -  Platelet count > 100,000/mm3

                    -  Hemoglobin ≥ 9 g/dL

                    -  Absolute neutrophil count (ANC) ≥ 1,000/mm3

               -  Hepatic:

                    -  Total Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

                    -  Except for patient with Gilbert's syndrome.

                    -  AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN

               -  Renal:

                    -  eGFR ≥ 30 mL/min/1.73m2 or creatinine clearance ≥ 30 mL/min by
                       Cockcroft-Gault:

                    -  Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72)

                    -  Females: (((140-age)×weight[kg])/(serum creatinine [mg/dL]×72))×0.85

          -  Concurrent enrollment in the study, "Rethinking Measurement of Performance Status in
             Cancer Patients," IRB 112529.

          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered post-menopausal if they have
             been amenorrheic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

               -  Women <50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy).

               -  Women ≥50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses >1 year ago, had
                  chemotherapy-induced menopause with last menses >1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy).

          -  Highly effective contraception for both male and female subjects throughout the study
             and for at least 5 months after the last dose of study therapy for females and 7
             months after the last dose for males if the risk of conception exists.

          -  Recovery to baseline or ≤ Grade 1 CTCAE v.5 from toxicities related to any prior
             treatments, unless AE(s) are clinically non-significant and/or stable on supportive
             therapy.

          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines.

        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).

          -  Diagnosis of any other malignancy within 2 years prior to study enrollment, except for
             adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the
             breast, bladder or of the cervix, and low-grade (Gleason 6 or below) prostate cancer
             on surveillance with no plans for treatment intervention (e.g., surgery, radiation, or
             castration) or prostate cancer that has been adequately treated with prostatectomy or
             radiotherapy and currently with no evidence of disease or symptoms is allowed.

          -  Uncontrolled CNS metastases are not allowed; subjects with previously treated brain
             metastases will be allowed if the brain metastases have been treated, toxicities have
             resolved to grade 1 or baseline and steroids are no longer required. Leptomeningeal
             metastases are not allowed.

               -  Patients with asymptomatic brain metastasis are allowed if previous steroid
                  treatment was discontinued ≥ 6 weeks.

               -  Patients with stable brain metastases on osimertinib therapy are eligible.

               -  Palliative radiation therapy is allowed while on study therapy (see Section 6.4).

          -  The subject has uncontrolled, significant intercurrent or recent illness including,
             but not limited to, the following conditions:

               -  Patients with known history or current symptoms of cardiac disease, or history of
                  treatment with cardiotoxic agents, should have a clinical risk assessment of
                  cardiac function using the New York Heart Association Functional Classification.
                  To be eligible for this trial, patients should be class 2B or better.

               -  Myocardial infarction, severe angina, or unstable angina within 6 months prior to
                  administration of first dose of study drug.

               -  Uncontrolled symptomatic hypertension that cannot be controlled with
                  anti-hypertensive agents.

               -  History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
                  ventricular fibrillation).

               -  Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial
                  fibrillation that is well controlled with anti-arrhythmic medication).

               -  Coronary or peripheral artery bypass graft within 6 months of screening.

               -  QTc prolongation > 500 msec.

               -  Active, clinically symptomatic left ventricular failure (left ventricle ejection
                  fraction (LVEF) < 50%).

               -  Other clinically significant disorders that would preclude safe study
                  participation.

          -  Known HIV infection with a detectable viral load within 6 months of the anticipated
             start of treatment.

             -Note: Patients on effective anti-retroviral therapy with an undetectable viral load
             within 6 months of the anticipated start of treatment are eligible for this trial.

          -  Known chronic hepatitis B virus (HBV) or hepatitis C virus infection with a detectable
             viral load.

             -Note: Patients with an undetectable HBV viral load on appropriate suppressive therapy
             are eligible. Patients with an undetectable HCV viral load on appropriate treatment
             are eligible.

          -  Vaccination with a live attenuated vaccine within 4 weeks of cycle one day one and
             while on trials is prohibited except for administration of inactivated vaccines.

          -  Known prior severe hypersensitivity to investigational product or any component in its
             formulations, including known severe hypersensitivity reactions to monoclonal
             antibodies (NCI CTCAE v5.0 Grade ≥ 3).

          -  Subjects taking prohibited medications as described in Section 6.4.2. A washout period
             of prohibited medications for a period of at least 5 half-lives or as clinically
             indicated should occur prior to the start of treatment.

          -  Subject is a prisoner or involuntarily incarcerated or is compulsorily detained for
             treatment of either a psychiatric or physical illness (e.g. infectious disease).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description: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 Outcome Measures

Measure:Efficacy of osimertinib in combination with ipilimumab: Objective response rate (ORR)
Time Frame:Patients will remain on treatment until progression and then followed for survival for 5 years from the end of treatment visit.
Safety Issue:
Description:Objective response rate (ORR) will be assessed by the number of patients obtaining a complete response plus the number of patients obtaining a partial response divided by the total number of response evaluable subjects.
Measure:Efficacy of osimertinib in combination with ipilimumab: Osimertinib progression free survival (oPFS)
Time Frame:PFS defined as the time between initiation of osimertinib and documented progression, death, or 5 yrs. from end of treatment
Safety Issue:
Description:Osimertinib progression free survival (oPFS) will be assessed as the time from the first dose of osimertinib until documented radiographic or clinical progression or death by any cause.
Measure:Efficacy of osimertinib in combination with ipilimumab: Ipilimumab progression free survival (iPFS)
Time Frame:iPFS defined as the time between the initiation of ipilimumab and documented progression, death, or 5 yrs from end of treatment
Safety Issue:
Description:Ipilimumab progression free survival (iPFS) as assessed as the time from the first dose of ipilimumab until documented radiographic or clinical progression or death by any cause.
Measure:Efficacy of osimertinib in combination with ipilimumab: Overall survival
Time Frame:will be assessed as the time between trial initiation and death of any cause up to 5 yrs after end of treatment
Safety Issue:
Description:Overall survival will be assessed as the time from trial initiation until death by any cause.
Measure:Efficacy of osimertinib in combination with ipilimumab
Time Frame: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.
Safety Issue:
Description:Time until the initiation of alternative anti-cancer therapy as defined as the time from radiographic progression until the first dose of alternative therapy.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

Last Updated

July 17, 2020