Clinical trial NCT03425331 (phase 2, status: suspended)
Conditions: non-small cell lung cancer
ICD codes: C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: ipilimumab, nivolumab
SMILES: COC1=CC=CC=C1OCC(O)CO, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    slow accrual, competing studies, and lack of efficacy
  
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.