Advanced Stage Non-small Cell Lung CancerPhase 2NCT02350764
Evaluate the Mediators of Sensitivity and Resistance to Nivolumab Plus Ipilimumab in Patients With Advanced NSCLCs
A Phase 2 study testing nivolumab and pilimumab in people with Advanced Stage Non-small Cell Lung Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to closely examine tumor and blood samples from patients treated with nivolumab and ipilimumab in order to try to identify why some patients with lung cancers respond and why some patients do not. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Stage Non-small Cell Lung Cancer
- What is being tested?
- nivolumab and pilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jan 2015to 25 Sep 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patient must be capable, willing, and able to provide written, informed consent.
- ≥ 18 years old.
- Advanced stage NSCLC
- Previously treated with no more than two lines of prior systemic therapy for advanced stage lung cancer.
- Patients who previously received neoadjuvant, concurrent, or adjuvant chemotherapy for localized NSCLC and then recurred within 6 months of completing chemotherapy may be considered as having received one line of prior therapy
- Maintenance therapy does not count as a separate line of therapy
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- Patients must:
- Be scheduled to undergo a standard-of-care resection of tumor tissue as part of treatment plan prior to beginning study therapy. Patients may not have intervening systemic anti-cancer therapy between the time of resection and treatment with nivolumab.
- Have collection of adequate pre-treatment tissue for correlative analysis defined as sufficient material for 1) frozen tissue for DNA/RNA with touch prep/representative slide confirming tumor material present, 2) FFPE material for ICH with touch prep/representative slide confirming tumor material present, and 3) single-cell suspensions with >20 million live cells after tissue digestion but before freezing. Adequacy of collected material will be determined within 5 business days of each collected case.
- Have residual disease following surgical resection that is measurable by RECIST v1.1
- Previously irradiated sites of tumor may be considered measurable if there is radiographic progression at that site subsequent to the time of completing radiation.
- Have a safely biopsiable tumor lesion
- ECOG performance status of 0-1.
- Adequate hematologic, renal, and/or hepatic function (following criteria must be met within 28 days of C1D1:
- WBC ≥ 2,000/ul
- ANC ≥ 1,500/ul
- Hemoglobin ≥ 9.0 g/dl
- Platelet count ≥ 100,000/ul
- Total bilirubin ≤ 1.5 x ULN (unless evidence of Gilbert's syndrome, in which case, direct bilirubin must be ≤ 1.0 x ULN)
- AST and ALT ≤ 3 x UNL (unless elevated transaminases are felt to be directly related to metastatic disease involving the liver, in which case AST and ALT must be ≤ 5x ULN)
- Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance of ≥ 40 mL/min calculated using the formula of Cockcroft and Gault: (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female
- There is no restriction on the number of prior lines of systemic anti-cancer therapy. For those who have received prior systemic anti-cancer therapy, there must be at least 3 weeks since last systemic therapy.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 3 days prior to the start of study drug.
- Effective contraception:
- Women of childbearing potential must agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 23 weeks (5 half-lifes plus 30 days, the duration of an ovulatory cycle) after the last dose of nivolumab, or agree to completely abstain from heterosexual intercourse.
- Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through 31 weeks (5 half-lives plus 90 days, the duration of sperm turnover) after the last dose of study drug, or completely abstain from heterosexual intercourse.
Who cannot join
- Patients who are pregnant or lactating.
- Presence of activating EGFR mutations or ALK re-arrangement,unless previously treated with standard TKI therapy. All patients with adenocarcinoma histology must be tested for EGFR and ALK status.
- History of allergy to study drug components or history of severe hypersensitivity reaction of any monoclonal antibody.
- Prior treatment with immune checkpoint inhibitor, including (but not limited to) those targeting PD-1, PD-L1, PD-L2, CTLA-4, CD137, GITR, TIM3, LAG3, or OX40
- Any systemic anti-cancer therapy within 3 weeks prior to C1D1 of study therapy
- Exception is made for patients with EGFR or ALK re-arrangements who must have stopped TKI therapy at least 7 days prior to C1D1
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- Patients who have not previously been treated with platinum-based based doublet chemotherapy and who, in the judgment of the investigator, have rapidly progressive disease such that serious complications may arise from disease progression within the next 12 weeks will be excluded.
- Non-CNS radiotherapy within 1 week prior to C1D1 of study therapy
- Active infection requiring therapy
- Prior systemic immunosuppressive therapy (> 10 mg/day prednisone equivalents) within 1 week prior to C1D1 of study therapy. Inhaled, ocular, intra-articular, intranasal, and topical corticosteroids are permitted in absence of active autoimmune disease.
- Adrenal replacement doses are permitted in the absence of active autoimmune disease.
- Patients with known or suspected history of autoimmune disease. Subjects with type I diabetes melitis, hypothyroidism only requiring hormone replacement, resolved childhood asthma/atopy, patients with asthma requiring intermittent bronchodilator therapy, 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.
- Other active malignancy requiring concurrent intervention.
- Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless definitive therapy has been completed at least 1 year prior to study entry and the patient is now without evidence of disease from that malignance and no additional therapy is required or anticipated to be required during the study period.
- Known untreated brain or leptomeningeal metastasis.
- o Patients with brain metastases are eligible if metastases have been adequately treated and neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least two weeks prior to C1D1. In addition, must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
- Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- Any positive test for HIV
- Any positive test for HCV RNA or HBsAg.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: An Exploratory Study to Evaluate the Mediators of Sensitivity and Resistance to Nivolumab Plus Ipilimumab in Patients With Advanced NSCLCs
The purpose of this study is to closely examine tumor and blood samples from patients treated with nivolumab and ipilimumab in order to try to identify why some patients with lung cancers respond and why some patients do not.
- Being tested
- nivolumab, pilimumab
- Keywords
- Nivolumab, Lung, ipilimumab, NSCLC, 14-137
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nivolumabDrug
pilimumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab | Experimental | Patients will begin treatment with nivolumab IV 3mg/kg and ipilimumab 1mg/kg. Treatment with nivolumab will continue every 2 weeks (+/- 3 days) thereafter and treatment with ipilimumab will continue every 6 weeks (+/- 3 days) thereafter. Treatment will continue until protocol-defined toxicity, confirmed progression of disease*, withdrawal of consent, or death. Receives: Drug: nivolumab; Drug: pilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rate (Confirmed Partial + Complete Response) Will be Assessed as Part of This Study. Tumor Response Will be Assessed Using RECIST 1.1)
confirmed partial + complete response will be assessed as part of this study. Tumor response will be assessed using RECIST 1.1. All responses must be confirmed on subsequent scan to be considered a true response. Tumor assessments will be performed after.6 weeks (+/- 1 week) and subsequently every six week (+/- 1 week) thereafter while on study until week 48. After week 48, tumor assessments will be conducted every 12 weeks (+/- week). Additional tumor assessments may be performed at the discretion of the treating physician.
Measured: every 6 weeks (+/- 1 week) until week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2015 (estimated)
- Study start20 Jan 2015
- Primary completion25 Sep 2023
- Study completion25 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Stage Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Adam Schoenfeld, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02350764
- Sponsor's protocol ID
- 14-137
- Status last verified
- Sep 2023
- First submitted
- 20 Jan 2015
- Last updated
- 29 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study to Evaluate the Mediators of Sensitivity and Resistance to Nivolumab Plus Ipilimumab in Patients With Advanced NSCLCs
- ClinicalTrials.gov ID
- NCT02350764
- Acronym / sponsor ID
- 14-137
- Keywords
- Nivolumab, Lung, ipilimumab, NSCLC, 14-137
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 20 Jan 2015 (actual)
- Primary completion
- 25 Sep 2023 (actual)
- Study completion
- 25 Sep 2023 (actual)
- First posted
- 30 Jan 2015 (estimated)
- Results
- Posted 29 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to closely examine tumor and blood samples from patients treated with nivolumab and ipilimumab in order to try to identify why some patients with lung cancers respond and why some patients do not.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab | Experimental | Drug: nivolumab, Drug: pilimumabPatients will begin treatment with nivolumab IV 3mg/kg and ipilimumab 1mg/kg. Treatment with nivolumab will continue every 2 weeks (+/- 3 days) thereafter and treatment with ipilimumab will continue every 6 weeks (+/- 3 days) thereafter. Treatment will continue until protocol-defined toxicity, confirmed progression of disease*, withdrawal of consent, or death. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Patient must be capable, willing, and able to provide written, informed consent.
- ≥ 18 years old.
- Advanced stage NSCLC
- Previously treated with no more than two lines of prior systemic therapy for advanced stage lung cancer.
- Patients must:
Key exclusion criteria (19 listed)
- Patients who are pregnant or lactating.
- Presence of activating EGFR mutations or ALK re-arrangement,unless previously treated with standard TKI therapy. All patients with adenocarcinoma histology must be tested for EGFR and ALK status.
- History of allergy to study drug components or history of severe hypersensitivity reaction of any monoclonal antibody.
- Prior treatment with immune checkpoint inhibitor, including (but not limited to) those targeting PD-1, PD-L1, PD-L2, CTLA-4, CD137, GITR, TIM3, LAG3, or OX40
- Any systemic anti-cancer therapy within 3 weeks prior to C1D1 of study therapy
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 |
|---|---|---|
| nivolumab | Drug | Nivolumab |
| pilimumab | Drug | Nivolumab |
Primary outcome
Best Overall Response Rate (Confirmed Partial + Complete Response) Will be Assessed as Part of This Study. Tumor Response Will be Assessed Using RECIST 1.1)
Time frame: every 6 weeks (+/- 1 week) until week 48
confirmed partial + complete response will be assessed as part of this study. Tumor response will be assessed using RECIST 1.1. All responses must be confirmed on subsequent scan to be considered a true response. Tumor assessments will be performed after.6 weeks (+/- 1 week) and subsequently every six week (+/- 1 week) thereafter while on study until week 48. After week 48, tumor assessments will be conducted every 12 weeks (+/- week). Additional tumor assessments may be performed at the discretion of the treating physician.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Adam Schoenfeld, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nivolumab and pilimumab in people with Advanced Stage Non-small Cell Lung Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site 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 26 inclusion and 19 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: finished, as of the sponsor's last update on 29 May 2024. 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 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?
Yes. Results are posted in the registry (first posted 29 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Best Overall Response Rate (Confirmed Partial + Complete Response) Will be Assessed as Part of This Study. Tumor Response Will be Assessed Using RECIST 1.1) (time frame: every 6 weeks (+/- 1 week) until week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 May 2024.