CA209-759: Blood-borne biomarkers for tumor response to Nivolumab in KRAS-mutated non-small cell lung cancer, an exploratory study

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 40

Inclusion Criteria

1. Histologically confirmed stage IIIB and stage IV NSCLC KRAS positive tumors only.
2. Available tumor tissue sample.
3. Prior palliative radiotherapy must have been completed at least 2 weeks prior to first dose nivolumab.
4. Any line of previous chemotherapy.
5. Nivolumab has to be the treatment that will be started.
6. At least one unidimensionally measurable lesion according to RECIST1.1 criteria.
7. Life expectancy more than 3 months.
8. ECOG PS 0-1.
9. Age18 years and older, both male and female subjects
10. Adequate organ functions
11. Signed informed consent.
12. Male and female patients with reproductive potential must use an approved contraceptive method,

Exclusion Criteria

1. Previous treatment with PD-1 or PD-L1 inhibitor.
2. Lung cancer previously treated for an ALK translocation, EGFR mutation or BRAF mutation
3. Pregnant or lactating women.
4. Patients who are poor medical risks because of non-malignant disease as well as those with active uncontrolled infection.
5. Patients without plasma sample at baseline (before treatment).
6. Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There 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.
7. Subjects with carcinomatous meningitis.
8. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization.
9. Subjects 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 a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
10. Other active malignancy requiring concurrent intervention.
11. Subjects 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.
12. 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 steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
13. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
14. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
15. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To discriminate, early in treatment, responders from non-responders to<br /><br>nivolumab in KRAS positive NSCLC.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>-Tumor response according RECIST1.1<br /><br>-To test (blood-borne and stool) biomarkers during nivolumab treatment to<br /><br>explore the predictive value for early tumor response (with one year survival<br /><br>as readout of response).<br /><br>-To develop a simple, affordable, diagnostic test using these data that can be<br /><br>rapidly adopted in clinical practice (e.g. ctDNA as biomarker in blood,<br /><br>calprotectin level in both stool and serum, peptides shared between the<br /><br>microbiota and the tumor that are identified by 16s RNA sequencing at baseline,<br /><br>serum IL-8, CRP, I-FABP, endotoxin and CRP-levels, or a combination). </p><br>

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