Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)Phase 1Osi+IpiNCT04141644

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

A Phase 1 study testing Ipilimumab and Osimertinib in people with Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder), run by University of Utah at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)
What is being tested?: Ipilimumab and Osimertinib
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteUnited States
Study dates: 20 Aug 2020to 30 Apr 2028
Phase: Phase 1
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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Hematologic:
White blood cell count > 2.0 k/microliter (uL)
Platelet count > 75,000/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
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," Institutional Review Board (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.

Who cannot join

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.

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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).
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.
Corrected QT interval (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 (HCV) 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).

Trial locations and contacts

1 site in 1 country.

United States1 site

Huntsman Cancer Institute
Salt Lake City, Utah, 84112

Other trials in United States

About this study

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

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

Read the 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.

Conditions: Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)
Being tested: Ipilimumab, Osimertinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IpilimumabDrug
Also called Bristol-Myers Squibb (BMS)-734016, Medarex (MDX)-010, Yervoy
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
OsimertinibDrug
Also called Tagrisso
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

Study groups in NCT04141644
Study group	Role	What they receive
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. Receives: Drug: Ipilimumab; Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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
Overall survival will be assessed as the time from trial initiation until death by any cause.
Measured: 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
Time until the initiation of alternative anti-cancer therapy as defined as the time from radiographic progression until the first dose of alternative therapy.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Aug 202030 Apr 2028

First posted28 Oct 2019
Study start20 Aug 2020
Primary completion29 Jan 2024
Study completion30 Apr 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (46)Papers the sponsor has linked to this study.
Other trials for Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)Studies of the same condition, open and under way.
More trials run by University of UtahThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: 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.
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04141644
Sponsor's protocol ID: HCI124882
Acronym: Osi+Ipi
Status last verified: May 2026
First submitted: 18 Oct 2019
Last updated: 19 May 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

American Cancer Society. Cancer Facts & Figures 2019. Atlanta:; 2019.
National Comprehensive Cancer Network. NCCN Guidelines Version 3.2019 Non-Small Cell Lung Cancer. NCCN; 2019.
Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, Hermes B, Cay Senler F, Csoszi T, Fulop A, Rodriguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. doi: 10.1056/NEJMoa1810865. Epub 2018 Sep 25.
PubMed 30280635
Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.
PubMed 29658856
Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.
PubMed 28885881
Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai CM, Tan EH, Ho JC, Chu da T, Zaatar A, Osorio Sanchez JA, Vu VV, Au JS, Inoue A, Lee SM, Gebski V, Yang JC. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2013 May 1;105(9):595-605. doi: 10.1093/jnci/djt072. Epub 2013 Apr 17.
PubMed 23594426
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29.
PubMed 15118073
Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 2008 Jul 24;359(4):366-77. doi: 10.1056/NEJMoa0800668. Epub 2008 Jul 2.
PubMed 18596266
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.
PubMed 19692680
Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. doi: 10.1016/S1470-2045(09)70364-X. Epub 2009 Dec 18.
PubMed 20022809
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. doi: 10.1056/NEJMoa0909530.
PubMed 20573926
Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Red Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Al-Kadhimi K, Rowlinson R, Klinowska T, Richmond GH, Cantarini M, Kim DW, Ranson MR, Pao W. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61. doi: 10.1158/2159-8290.CD-14-0337. Epub 2014 Jun 3.
PubMed 24893891
Janne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. doi: 10.1056/NEJMoa1411817.
PubMed 25923549
Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.
PubMed 27959700
Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.
PubMed 29151359

Study at a glance

From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04141644
Acronym / sponsor ID: Osi+Ipi / HCI124882
Conditions: Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)
Phase: Phase 1
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 24 participants (actual)
Lead sponsor: University of UtahUniversity, hospital or other
Collaborators: Bristol-Myers Squibb
Study start: 20 Aug 2020 (actual)
Primary completion: 29 Jan 2024 (actual)
Study completion: 30 Apr 2028 (estimated)
First posted: 28 Oct 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: 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.

Arm	Type	Receives
Treatment: all patients	Experimental	Drug: Ipilimumab, Drug: OsimertinibPatients 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (26 listed)

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.

Key exclusion criteria (33 listed)

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:
Current use of immunosuppressive medication at the time of study enrollment, EXCEPT for the following permitted steroids:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IpilimumabAlso: Bristol-Myers Squibb (BMS)-734016, Medarex (MDX)-010, YervoyCohort 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	Drug	Treatment: all patients
OsimertinibAlso: TagrissoCohort 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	Drug	Treatment: all patients

Primary outcome

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.

5 secondary outcomes

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.
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
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
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
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.

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
BackgroundAmerican Cancer Society. Cancer Facts & Figures 2019. Atlanta:; 2019.
BackgroundNational Comprehensive Cancer Network. NCCN Guidelines Version 3.2019 Non-Small Cell Lung Cancer. NCCN; 2019.
Background: PubMed 30280635Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, Hermes B, Cay Senler F, Csoszi T, Fulop A, Rodriguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. doi: 10.1056/NEJMoa1810865. Epub 2018 Sep 25.
Background: PubMed 29658856Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.
Background: PubMed 28885881Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.
Background: PubMed 23594426Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai CM, Tan EH, Ho JC, Chu da T, Zaatar A, Osorio Sanchez JA, Vu VV, Au JS, Inoue A, Lee SM, Gebski V, Yang JC. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2013 May 1;105(9):595-605. doi: 10.1093/jnci/djt072. Epub 2013 Apr 17.
Background: PubMed 15118073Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29.
Background: PubMed 18596266Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 2008 Jul 24;359(4):366-77. doi: 10.1056/NEJMoa0800668. Epub 2008 Jul 2.
Background: PubMed 19692680Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.
Background: PubMed 20022809Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. doi: 10.1016/S1470-2045(09)70364-X. Epub 2009 Dec 18.
Background: PubMed 20573926Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. doi: 10.1056/NEJMoa0909530.
Background: PubMed 24893891Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Red Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Al-Kadhimi K, Rowlinson R, Klinowska T, Richmond GH, Cantarini M, Kim DW, Ranson MR, Pao W. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61. doi: 10.1158/2159-8290.CD-14-0337. Epub 2014 Jun 3.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Matthew Gumbleton, MD principal investigator

Huntsman Cancer Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04141644, which also lists 46 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.