Clinical Trials /

Biomarkers of Response to Ipilimumab and Nivolumab in First-line NSCLC

NCT03425331

Description:

This research study is studying two immunotherapy drugs as a possible treatment for advanced non-small cell lung cancer (NSCLC). The drugs involved in this study are: - Ipilimumab - Nivolumab

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Biomarkers of Response to Ipilimumab and Nivolumab in First-line NSCLC
  • Official Title: Biomarkers of Response to Ipilimumab and Nivolumab as First-line Therapy for Metastatic Non-small Cell Lung Cancer (NSCLC): an Open-label, Single Arm Phase 2 Study

Clinical Trial IDs

  • ORG STUDY ID: 17-566
  • NCT ID: NCT03425331

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
IpilimumabYervoyNivolumab+Ipilimumab
NivolumabOpdivoNivolumab+Ipilimumab

Purpose

This research study is studying two immunotherapy drugs as a possible treatment for advanced non-small cell lung cancer (NSCLC). The drugs involved in this study are: - Ipilimumab - Nivolumab

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of investigational drugs to learn whether the drugs work in treating a
      specific disease. "Investigational" means that the drugs are being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved ipilimumab for this specific
      disease but it has been approved for other uses, including for patients with advanced
      melanoma.

      The FDA (the U.S. Food and Drug Administration) has approved nivolumab as a treatment option
      for this disease. However, nivolumab it is not approved in combination with ipilimumab to
      treat NSCLC.

      Nivolumab and ipilimumab are both types of immunotherapy. Immunotherapy works by stimulating
      the body's own immune system to attack cancer cells. The combination of ipilimumab with
      nivolumab may or may not increase anti-cancer activity by further boosting the immune system.

      In this research study, the investigators are investigating if the combination of ipilimumab
      and nivolumab is effective in treating advanced NSCLC. The investigators are also
      investigating whether there are certain DNA or protein markers in the blood or tumor tissue
      that may indicate whether the combination will work in future patients.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab+IpilimumabExperimentalNivolumab will be administered once every 2 weeks intravenously Ipilimumab will be administered once every 6 weeks intravenously
  • Ipilimumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed stage IV NSCLC, with no prior systemic anti-cancer therapy of
             any kind (including EGFR and ALK inhibitors). Prior definitive chemoradiation for
             locally advanced disease is permitted as long as the last administration of
             chemotherapy or radiation (whichever was given last) occurred at least 6 months prior
             to enrollment. Prior adjuvant or neoadjuvant chemotherapy for early stage lung cancer
             is permitted if completed at least 6 months prior to initiating study treatment.

          -  Participants must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional
             techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See
             Section 11 for the evaluation of measurable disease.

          -  Age ≥ 18 years.

          -  ECOG performance status ≤ 1 (see Appendix A)

          -  Participants must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count ≥ 1,500/mcL

               -  Platelets ≥ 100,000/mcL

               -  Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

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

               -  AST(SGOT)/ALT(SGPT) ≤ 5 × institutional ULN if liver metastases are present

               -  Serum creatinine ≤ 1.5 × institutional ULN, OR

               -  Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with serum creatinine
                  levels above 1.5 × institutional ULN.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Participants must have a tumor tissue sample available (formalin-fixed paraffin
             embedded [FFPE] tissue block or unstained slides); may be newly obtained or obtained
             within 6 months prior to enrollment (without systemic therapy given after the sample
             was obtained). Participants without sufficient archival tissue may be enrolled
             following successful completion of the pre-treatment tumor tissue biopsy. Tissue must
             be a core needle biopsy, excisional, or incisional biopsy. Fine needle aspirates (FNA)
             or malignant effusions are not adequate. Bone biopsies without a soft tissue component
             are not adequate.

          -  The effects of nivolumab and ipilimumab on the developing human fetus are unknown. For
             this reason, women of childbearing potential (WOCBP) must agree to follow instructions
             for acceptable contraception from the time of signing consent, and for 23 weeks after
             their last dose of protocol-indicated treatment. Should a woman become pregnant or
             suspect she is pregnant while she or her partner is participating in this study, she
             should inform her treating physician immediately. Men treated or enrolled on this
             protocol who are not azoospermic who are sexually active with WOCBP must agree to
             follow instructions for acceptable contraception from the time of signing consent, and
             for 31 weeks after their last dose of protocol-indicated treatment.

          -  Participants must be able and willing to undergo a pre-treatment tumor tissue biopsy.
             Participants must also be willing to undergo an on-treatment tumor tissue biopsy if
             clinically feasible.

        Exclusion Criteria:

          -  Participants with known EGFR mutations or ALK rearrangements. All subjects must have
             been tested for EGFR mutation and ALK rearrangement prior to study entry, unless they
             are known to have a KRAS mutation.

          -  Participants who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2,
             anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell
             co-stimulation or checkpoint pathways.

          -  Participants who received prior non-CNS directed palliative radiation therapy within 7
             days of the date of study entry.

          -  Participants who are receiving any other investigational agents.

          -  Participants with known untreated brain metastases should be excluded from this
             clinical trial because of their poor prognosis and because they often develop
             progressive neurologic dysfunction that would confound the evaluation of neurologic
             and other adverse events. 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 study
             entry. 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 first study
             treatment.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ipilimumab or nivolumab.

          -  Participants with previous malignancies are excluded unless a complete remission was
             achieved at least 2 years prior to first treatment and no additional therapy is
             required or anticipated to be required during the study period as judged by the
             treating investigator. Exceptions include non-melanoma skin cancers, and in situ
             cancers of any type (e.g. bladder, gastric, colon, cervical/dysplasia, melanoma, or
             breast carcinoma in situ).

          -  Participants with any other active malignancy requiring concurrent intervention.

          -  Participants with an active, known, or suspected autoimmune disease. Subjects with
             type I diabetes mellitus, hypothyroidism only requiring 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.

          -  Participants with a condition requiring systemic treatment with corticosteroids of >
             10 mg daily prednisone (or equivalent), or subjects requiring other immunosuppressive
             medications within 14 days of first treatment. Inhaled, topical, ophthalmologic, local
             steroid injections, and adrenal replacement steroid > 10 mg daily prednisone or
             equivalent are permitted in the absence of active autoimmune disease.

          -  Participants with interstitial lung disease that is symptomatic or may interfere with
             the detection or management of suspected drug-related pulmonary toxicity in the
             opinion of the treating investigator.

          -  Participants with a known history of testing positive for human immunodeficiency virus
             (HIV), or known acquired immunodeficiency syndrome (AIDS).

          -  Participants with known positive test for hepatitis B or C indicating acute or chronic
             infection.

          -  Participants with ≥ Grade 2 peripheral neuropathy.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because ipilimumab and nivolumab are both
             agents with the potential for teratogenic or abortifacient effects. Because there is
             an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with ipilimumab or nivolumab, breastfeeding should be
             discontinued if the mother is treated with ipilimumab or nivolumab. A negative serum
             pregnancy test is required prior to study entry.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best overall objective response rate
Time Frame:2 years
Safety Issue:
Description:RECIST1.1 measurements of CT scans will be measured during treatment to determine the objective response rate for patients being treated with nivolumab and ipilimumab.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:Time from registration to documented disease progression or death from any cause, whichever occurs first. The Kaplan-Meier method will be used to determine the progression-free survival.
Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:Time from registration to death from any cause. The Kaplan-Meier method will be used to calculate overall survival.
Measure:Duration of response
Time Frame:2 years
Safety Issue:
Description:Time from tumor response to documented disease progression or death from any cause, whichever occurs first.
Measure:Toxicity
Time Frame:2 years
Safety Issue:
Description:• Determined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Non-Small Cell Lung Cancer

Last Updated

February 1, 2018