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Carcinoma, Non-Small-Cell LungPhase 2G360-IITNCT05715229

Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy

A Phase 2 study testing Nivolumab, Ipilimumab and Carboplatin in people with Carcinoma, Non-Small-Cell Lung, run by Hackensack Meridian Health at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This clinical trial plans to assess to what extent the on-treatment circulating tumor DNA (ctDNA) can predict the subset of patients with NSCLC who will respond to immunotherapy treatment only and which patients will need both immunotherapy and chemotherapy modalities for their treatment regimen. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Nivolumab, Ipilimumab and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
3 sitesUnited States
Study dates
29 Sep 2023to 13 Aug 2026
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Eligible patients will have newly diagnosed, previously untreated histologically documented Stage IV NSCLC
  • Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay.
  • Patients will require a baseline Guardant360 CDx test prior to enrollment
  • Patients willing to undergo serial ctDNA testing as required by protocol
  • Patients will be over the age of 18
  • Life expectancy ≥12 weeks
Show all 17Show fewer
  • Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per the treating investigator.
  • Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization
  • ECOG Performance Score ≤2
  • Adequate organ function
  • Hemoglobin > 9 g/dL
  • Platelets > 100,000mm3 or 100 x 109/L
  • AST, ALT < 2.5 x ULN with no liver metastases or < 5x ULN with the presence of liver metastases
  • Total bilirubin < 1.5 x ULN if no liver metastases or < 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
  • Absolute neutrophil count (ANC) > 1500 cells/mm3
  • Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault's equation
  • Willing to use highly effective contraceptive measures if child-bearing potential or if the patient's sexual partner is a woman of childbearing potential: a. Female subjects should be using a highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to starting of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: i. Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not a tubal ligation b. Male subjects should be willing to use barrier contraception

Who cannot join

  • Patients under the age of 18
  • Inability to provide informed consent by either the patient or the authorized representative
  • Patients with known EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations that have approved first-line targeted therapies are excluded from the study (All patients must have a tissue or blood-based testing to identify these driver alterations)
  • Patients with no detectable ctDNA or ctDNA VAF ≤ 0.3% on Guardant360 CDx at baseline
  • Subjects with untreated CNS metastases are excluded.
  • Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.
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  • Subjects with carcinomatous meningitis
  • Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization
  • Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to randomization and no additional therapy is required or anticipated to be needed during the study period.
  • Other active malignancy requiring concurrent intervention.
  • Subjects with an active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, and hypothyroidism only require hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroids > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  • Significant uncontrolled cardiovascular disease, including but not limited to, any of the following:
  • Uncontrolled hypertension, which is defined as systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg despite optimal medical management.
  • Active coronary artery disease, including unstable all newly diagnosed angina within 3 months of study enrollment.
  • Myocardial infarction in the past 6 months.
  • History of congenital long QT syndrome.
  • History of clinically significant arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes.
  • Uncontrolled heart failure, defined as class III of 4 by the New York Heart Association functional classification.
  • History of a current diagnosis of myocarditis.
  • the Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
  • Subjects with Grade 2 peripheral neuropathy
  • Life expectancy <12 weeks

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • John Theurer Cancer Center, Hackensack Meridian Health

    Hackensack, New Jersey, 07410

  • Jersey Shore University Medical Center

    Neptune City, New Jersey, 07753

  • Lombardi Comprehensive Cancer Center, Georgetown University

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Multicenter Phase II Randomized Trial Of Immunotherapy Versus Chemotherapy Guided By Circulating Tumor DNA-Based Molecular Response On Patients With Metastatic NSCLC

This clinical trial plans to assess to what extent the on-treatment circulating tumor DNA (ctDNA) can predict the subset of patients with NSCLC who will respond to immunotherapy treatment only and which patients will need both immunotherapy and chemotherapy modalities for their treatment regimen.

Read the detailed description

Subjects will be randomized 2:1 and patients in both arms will begin treatment with nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the larger arm will receive treatment based on the Guardant360 Response assay results, as described below. Subjects will undergo ctDNA evaluation with Guardant360 Response assay 6- week post-randomization and at the time of progression. Response to therapy will be assessed by interval imaging with CT scan of the chest/abdomen/pelvis (and MRI brain if applicable) with response evaluated by irRECIST criteria every 12 weeks until disease progression.

Keywords
Advanced Non Small Cell Lung Cancer (NSCLC), Metastatic NSCLC, circulating tumor DNA (ctDNA), G360
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

Study groups in NCT05715229
Study groupRoleWhat they receive
Arm AActive comparatorArm A - Intervention arm (Immunotherapy and Chemotherapy) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks Platinum- doublet Chemotherapy (Histology-based) 4 cycles depending on the investigator's discretion. Carboplatin dosed at AUC 5, and either Paclitaxel 175 mg/m2 for squamous or Pemetrexed 500 mg/m2 for non-squamous
Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed
Arm BOtherArm B - control arm (Immunotherapy only) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

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

  1. Progression Free Survival (PFS)

    To compare progression free survival in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results.

    Measured: Time from randomization to objective disease progression, or death from any cause, whichever first, up to 36 months

Secondary outcomes (5)

  1. Progression Free Survival on Subsequent line of therapy (PFS2)

    To compare progression free survival on subsequent line of therapy (PFS2) between patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results

    Measured: Duration of time from randomization to second objective disease progression, or death from any cause, whichever first, up to 36 months

  2. Overall Survival

    To compare overall survival (OS) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results

    Measured: Duration of time from first treatment to time of death, up to 36 months

  3. Objective Response Rate

    To compare objective response rate (ORR) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on treatment-ctDNA results.

    Measured: Duration of time between the date of first treatment and the date of objectively documented progression per irRECIST or the date of initiation of palliative local therapy or the date of subsequent anti-cancer therapy, whichever occurs first, up to 36 mo

  4. Duration of Response

    To compare duration of response (DOR) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results.

    Measured: Duration of time between the date of first confirmed response to the date of the first documented tumor progression (per irRECIST), or death due to any cause, whichever occurs first, up to 36 months

  5. Safety and Tolerability

    Serious adverse events will be summarized by treatment group as number and percentages. Overall summary of SAEs by grade (any grade, grade 3-4, grade 5) will be reported. Overall summary of drug-related SAEs by worst CTC grade (any grade, grade 3-4, grade 5) will be reported.

    Measured: All analyses will be conducted using the 30-day safety window

Timeline

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

  1. First posted6 Feb 2023
  2. Study start29 Sep 2023
  3. Primary completion13 Aug 2026
  4. Study completion13 Aug 2026

Why it stopped: Slow Accrual

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Subjects will be randomized 2:1 and patients in both arms will begin treatment with nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the arm A will receive treatment based on the Guardant360 Response assay results, as described below. Arm B will continue the immunotherapy only.
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05715229
Sponsor's protocol ID
Pro2022-0016
Acronym
G360-IIT
Status last verified
Sep 2026
First submitted
6 Jan 2023
Last updated
23 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Goldberg SB, Narayan A, Kole AJ, Decker RH, Teysir J, Carriero NJ, Lee A, Nemati R, Nath SK, Mane SM, Deng Y, Sukumar N, Zelterman D, Boffa DJ, Politi K, Gettinger SN, Wilson LD, Herbst RS, Patel AA. Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA. Clin Cancer Res. 2018 Apr 15;24(8):1872-1880. doi: 10.1158/1078-0432.CCR-17-1341. Epub 2018 Jan 12.

    PubMed 29330207

  • Hellmann MD, Nabet BY, Rizvi H, Chaudhuri AA, Wells DK, Dunphy MPS, Chabon JJ, Liu CL, Hui AB, Arbour KC, Luo J, Preeshagul IR, Moding EJ, Almanza D, Bonilla RF, Sauter JL, Choi H, Tenet M, Abu-Akeel M, Plodkowski AJ, Perez Johnston R, Yoo CH, Ko RB, Stehr H, Gojenola L, Wakelee HA, Padda SK, Neal JW, Chaft JE, Kris MG, Rudin CM, Merghoub T, Li BT, Alizadeh AA, Diehn M. Circulating Tumor DNA Analysis to Assess Risk of Progression after Long-term Response to PD-(L)1 Blockade in NSCLC. Clin Cancer Res. 2020 Jun 15;26(12):2849-2858. doi: 10.1158/1078-0432.CCR-19-3418. Epub 2020 Feb 11.

    PubMed 32046999

  • Guibert N, Jones G, Beeler JF, Plagnol V, Morris C, Mourlanette J, Delaunay M, Keller L, Rouquette I, Favre G, Pradines A, Mazieres J. Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer. Lung Cancer. 2019 Nov;137:1-6. doi: 10.1016/j.lungcan.2019.09.005. Epub 2019 Sep 6.

    PubMed 31518912

  • Herbreteau G, Langlais A, Greillier L, Audigier-Valette C, Uwer L, Hureaux J, Moro-Sibilot D, Guisier F, Carmier D, Madelaine J, Otto J, Souquet PJ, Gounant V, Merle P, Molinier O, Renault A, Rabeau A, Morin F, Denis MG, Pujol JL. Circulating Tumor DNA as a Prognostic Determinant in Small Cell Lung Cancer Patients Receiving Atezolizumab. J Clin Med. 2020 Nov 27;9(12):3861. doi: 10.3390/jcm9123861.

    PubMed 33261056

  • Ricciuti B, Jones G, Severgnini M, Alessi JV, Recondo G, Lawrence M, Forshew T, Lydon C, Nishino M, Cheng M, Awad M. Early plasma circulating tumor DNA (ctDNA) changes predict response to first-line pembrolizumab-based therapy in non-small cell lung cancer (NSCLC). J Immunother Cancer. 2021 Mar;9(3):e001504. doi: 10.1136/jitc-2020-001504.

    PubMed 33771889

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

    PubMed 30207593

  • Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12.

    PubMed 33433946

  • Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020 Aug 13;383(7):640-649. doi: 10.1056/NEJMoa1916623.

    PubMed 32786189

  • Reinmuth N, Reck M. Immunotherapy for Lung Cancer. Oncol Res Treat. 2016;39(6):360-8. doi: 10.1159/000446726. Epub 2016 May 25.

    PubMed 27259861

  • Laoui D, Van Overmeire E, De Baetselier P, Van Ginderachter JA, Raes G. Functional Relationship between Tumor-Associated Macrophages and Macrophage Colony-Stimulating Factor as Contributors to Cancer Progression. Front Immunol. 2014 Oct 7;5:489. doi: 10.3389/fimmu.2014.00489. eCollection 2014.

    PubMed 25339957

  • Postow MA, Harding J, Wolchok JD. Targeting immune checkpoints: releasing the restraints on anti-tumor immunity for patients with melanoma. Cancer J. 2012 Mar-Apr;18(2):153-9.

    PubMed 22453017

  • Zhang Y, Huang S, Gong D, Qin Y, Shen Q. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol. 2010 Sep;7(5):389-95. doi: 10.1038/cmi.2010.28. Epub 2010 May 31.

    PubMed 20514052

  • Ang YL, Lim JS, Soo RA. Profile of nivolumab in the treatment of metastatic squamous non-small-cell lung cancer. Onco Targets Ther. 2016 May 30;9:3187-95. doi: 10.2147/OTT.S84356. eCollection 2016.

    PubMed 27313464

  • Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015 Mar;16(3):257-65. doi: 10.1016/S1470-2045(15)70054-9. Epub 2015 Feb 20.

    PubMed 25704439

  • Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, Poddubskaya E, Borghaei H, Felip E, Paz-Ares L, Pluzanski A, Reckamp KL, Burgio MA, Kohlhaeufl M, Waterhouse D, Barlesi F, Antonia S, Arrieta O, Fayette J, Crino L, Rizvi N, Reck M, Hellmann MD, Geese WJ, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Eberhardt WEE. Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017 Dec 10;35(35):3924-3933. doi: 10.1200/JCO.2017.74.3062. Epub 2017 Oct 12.

    PubMed 29023213

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Ipilimumab and Carboplatin in people with Carcinoma, Non-Small-Cell Lung, run by Hackensack Meridian Health at 3 sites in United States.

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 17 inclusion and 25 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: stopped early, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was stopped early (reason given: Slow Accrual). Results are not available in the source record.

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?

Progression Free Survival (PFS) (time frame: Time from randomization to objective disease progression, or death from any cause, whichever first, up to 36 months). 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 NCT05715229, which also lists 30 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 23 Sep 2026.

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