Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Nivolumab

Ipilimumab

Nintedanib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Nivolumab + Ipilimumab + Nintedanib dose escalation.

Nivolumab: 3 mg/kg IV Q2 weeks.

Ipilimumab: 1 mg/kg Q6 weeks.

Nintedanib Level -1: 100 mg by mouth (PO) once a day (QD) Days 1-14 (Daily dose =100 mg).

Nintedanib Level 0:150 mg by mouth (PO) once a day (QD) Days 1-14 (Daily dose =150 mg)

Nintedanib Level 1: 100 mg PO twice daily (BID) Days 2-28 (Daily dose = 200 mg).

Nintedanib Level 2: 150 mg PO BID Days 1-14 (Daily dose = 300 mg).

Nintedanib Level 3: 200 mg PO BID Days 1-14 (Daily dose = 400 mg).

Arm A: Newly diagnosed or treatment-naïve patients, with a target overall response rate (ORR) of 50%.

Nivolumab + Ipilimumab + Nintedanib at RP2D.

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%.

Nivolumab + Ipilimumab + Nintedanib at RP2D.

Nintedanib 100-200 mg capsules by mouth twice daily for two-week cycles.

Jhanelle E. Gray, M.D.

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.

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

Dose escalation to determine the MTD and Recommended Phase 2 Dose (RP2D) of concurrent administration of nivolumab, ipilimumab, and nintedanib. The maximum tolerated dose (MTD) is defined as the dose with the dose limiting toxicity (DLT) rate of 30%.

Objective response is defined as confirmed CR or confirmed PR based on modified RECIST guidelines version 1.1. The ORR will be estimated by calculating the proportion of patients who achieve OR; the 80% Confidence Interval (CI) and 95% CI for the OR rate will be estimated using the exact binomial distribution. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Disease control is defined as CR, PR, or SD based on RECIST guidelines version 1.1 with modifications. The disease control rate (DCR) will be estimated by the proportion of patients who achieve DC, and its 80% CI and 95% CI will be estimated using the exact binomial distribution. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Overall survival will be determined as the time from the start of treatment with nivolumab plus ipilimumab plus nintedanib until death due to any cause. For patients who are alive at the time of data cut-off, OS will be censored on the last date when patients are known to be alive. The Kaplan-Meier method will be used to estimate the OS curve and the OS rate at time points of interest.

Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

Spots Global Cancer Trial Database for Phase I/II Study of Nivolumab and Ipilimumab Combined With Nintedanib in Non Small Cell Lung Cancer

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