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Clinical Trial 19406

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT03377023

Phase: Phase I/II
Principal Investigator: Gray, Jhanelle

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

Phase I/II Study of Nivolumab and Ipilimumab combined with Nintedanib in Non Small Cell Lung Cancer

Summary

The main purpose of this study is to see if the combination of nivolumab, ipilimumab and nintedanib is effective in people with non- small cell lung cancer. Researchers also want to find out if the combination of nivolumab, ipilimumab and nintedanib is safe and tolerable.

Objective

Phase I (Dose Escalation): Determine the MTD and RP2D of concurrent administration of nivolumab, ipilimumab, and nintedanib. Phase II (Single Arm Cohorts): To determine the efficacy of concurrent administration of nivolumab, ipilimumab, and nintedanib in NSCLC patients. (1) Arm A: Newly diagnosed or treatment-naïve patients, with a target ORR of 50%, or (2) Arm B: Patients who have been previously exposed to immunotherapy, such as anti-PD-1, anti-PD-L1 or anti-CTLA-4, with a target ORR of 20%.

Treatments

Therapies

Immunotherapy; Therapy (NOS)

Medications

BMS-936558 (Nivolumab); Ipilimumab (); Nintedanib (); Nivolumab (Opdivo); Yervoy (Ipilimumab)

Inclusion Criteria

Participants must have histologic or cytological diagnosis of advanced/metastatic Non-Small Cell Lung Cancer (NSCLC) with no curative treatment options. For those with mixed histology, there must be a predominant histology.

18 years of age or older on day of signing informed consent.

Life expectancy of at least 3-6 months.

Eastern Cooperative Oncology Group (ECOG) performance status score 0 and 1

For phase I trial portion, treatment naïve or patients previously treated with chemotherapy, immunotherapy or targeted therapy for NSCLC are allowed. Patient who underwent curative intent chemotherapy and/radiation in the neoadjuvant or adjuvant setting are allowed to enroll if tumor recurrence occurred greater than 6 months from completion of that therapy. Patients with NSCLC tumor known to harbor a genomic aberration for which FDA approved treatment is available are allowed to enroll if they have received prior treatment with the FDA approved targeted therapy.

For phase II trial portion, Patients will be enrolled as 2 parallel cohorts: A.) Arm A (treatment naïve): Patients who are newly diagnosed and treatment naïve. Patient who underwent curative intent chemotherapy and/radiation in the neoadjuvant or adjuvant setting are allowed to enroll if tumor recurrence occurred greater than 6 months from completion of therapy. Patients with NSCLC tumor known to harbor a genomic aberration for which FDA approved treatment is available are allowed to enroll if they have received prior treatment with the FDA approved targeted therapy. B.) Arm B (immunotherapy pre-treated group): Patients who have received prior immunotherapy. Patients who are primary refractory to immunotherapy or have relapsed disease. Patients with NSCLC tumor known to harbor a genomic aberration for which FDA approved treatment is available are allowed to enroll if they have received prior treatment with the FDA approved targeted therapy.

At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

QTcB must be > Adequate normal organ and marrow function

Have archival tissue where available.

Willing and able to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Patients for whom newly obtained samples cannot be provided may submit an archived specimen upon agreement from the Sponsor.

Female participants of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Ability to understand and willingness to provide written informed consent signed and dated prior to admission to the study in accordance with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.

Exclusion Criteria

Concurrent use of other anticancer agents or other investigational drugs or treatment in another clinical trial with a non- FDA-approved medication within past 4 weeks before start of therapy.

Chemo-, or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within past 2 weeks prior to treatment with trial drug.

Radiotherapy (except brain and extremities or stereotactic treatment) within past 2 weeks prior to treatment with trial drug.

In immunotherapy pretreated patients, history of dose-limiting toxicity with prior immunotherapy agents.

Prior nintedanib treatment.

Known hypersensitivity to nintedanib, nivolumab, ipilimumab, peanut or soy or any other trial drug, or their excipients.

Toxicity from previous anti-cancer therapy that has not resolved to a Grade 1. Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included.

History of leptomeningeal carcinomatosis.

Radiotherapy to a target lesion within past 3 months prior to baseline imaging unless that area has demonstrated progression.

Active brain metastases; dexamethasone therapy allowed if administered as stable or decreasing dose for at least 3 weeks before randomization otherwise no steroids to exceed prednisone 10 mg/day prior to starting trial treatment. Symptomatic or uncontrolled CNS metastasis.

Current or prior use of immunosuppressive medication 7 days before first dose of nivolumab or ipilimumab, with exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. A brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions is permitted. Topical corticosteroids are permitted..

Active or prior documented autoimmune disease within past 2 years. Some exceptions apply.

Centrally located tumors with radiographic evidence of local invasion of major blood vessels.

Known history/evidence of active, non-infectious pneumonitis.

Therapeutic anticoagulation with drugs requiring INR monitoring (some exceptions apply) or antiplatelet therapy.

Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during on-treatment study period.

History of clinically significant hemorrhagic or thromboembolic event in past 6 months.

Known inherited predisposition to bleeding or thrombosis.

Significant cardiovascular diseases.

Coagulation parameters: INR > 2, PT and PTT > 50% of deviation of IULN.

Another primary malignancy within past 2 years except for: Basal cell skin cancer; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated carcinoma in situ without evidence of disease.

Active serious infections if requiring systemic antibiotic or antimicrobial therapy

Known active Hepatitis B or Hepatitis C

History of known active primary immunodeficiency

History of allogeneic organ transplant

Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study treatment.

Gastrointestinal disorders or abnormalities that would interfere with absorption of study drug

Serious illness or concomitant non-oncological disease that may increase the risk associated with study participation or study drug administration

Sexually active and unwilling to use a medically acceptable method of contraception during the trial and after end of active therapy

Pregnancy or breastfeeding.

Additional criteria may apply

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