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

NCT04141644 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCI124882
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Short and Long term tolerability of ipilimumab in combination with osimertinib: Adverse Events (AEs)

  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.

  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.

Secondary Outcomes (5)

• 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.

Study Arms (1)

Treatment: all patients

EXPERIMENTAL

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.

Drug: Ipilimumab; Drug: Osimertinib

Interventions

Ipilimumab DRUG

Cohort 1: Osi 40 mg or 80 mg daily; Ipi 3 mg/kg every 3 weeks Cohort 2: Osi 40 mg or 80 mg daily; Ipi 1 mg/kg every 3 weeks

Also known as: Bristol-Myers Squibb (BMS)-734016, Medarex (MDX)-010, Yervoy

Treatment: all patients

Osimertinib DRUG

Cohort 1: Osi 40 mg or 80 mg daily; Ipi 3 mg/kg every 3 weeks Cohort 2: Osi 40 mg or 80 mg daily; Ipi 1 mg/kg every 3 weeks

Also known as: Tagrisso

Treatment: all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤ 2.
• 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
• 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.
• Aspartate aminotransferase (AST)(SGOT)/Alanine aminotransferase (ALT)(SGPT) ≤ 2.5 × institutional ULN

You may not qualify if:

• 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 central nervous system (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).

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

Ipilimumab; CTLA-4 Antigen; osimertinib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Matthew Gumbleton, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase 1b, open label study of osimertinib in combination with ipilimumab in eligible adult patients with locally advanced or metastatic EGFR mutated non-small cell lung cancer. The study will focus on the safety and long term tolerability of the combination. The study will begin with a safety lead-in evaluation consisting of a cohort of six patients. Once safety has been established, the trial will open enrollment to the expansion cohort. The expansion cohort will enroll an additional 14 patients at the same doses evaluated during the safety lead-in.

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: October 28, 2019
• Study Start: August 20, 2020
• Primary Completion: January 29, 2024
• Study Completion (Estimated): April 30, 2028
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)