A Randomized Phase II Trial of Cabozantinib and Cabozantinib Plus Nivolumab Versus Standard Chemotherapy in Patients with Previously Treated Non-Squamous NSCLC

Protocol: ECOG – EA5191

SCHEMA EA9181

Please Note: Below is partial eligibility, for full eligibility requirement’s, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 and/or    (810) 762-8038. Thank you!

Eligibility:

1. Must be at least 18 years of age.
2. Patient must have pathologically confirmed non-squamous non-small cell lung carcinoma (NSCLC).
3. Patient must have Stage IV disease (includes M1a, M1b, or recurrent earlier stage disease), according to the 8th edition of the lung cancer TNM classification system.
4. Patient must have predominant non-squamous histology (patients with NSCLC NOS are eligible). Mixed tumors will be categorized by the predominant cell type. If small cell elements are present the patient is ineligible.
5. Patient’s tumor(s) must be tested and known negative for EGFR TKI sensitizing mutations (EGFR Exon 19 deletions, L858R, L861Q, G719X) and ALK gene rearrangements (by FISH, NGS, or IHC) by routine CLIA-certified clinical testing methods. Negative circulating tumor DNA results alone are not acceptable. Prior testing for tumor PD-L1 status is not required.
6. Patients WITHOUT tumors with known molecular alterations in ROS1, MET, RET (see below), or must have progressed radiographically (per local investigator assessment) following one, but only one, line of platinum-based chemotherapy AND one, but only one, line of prior immunotherapy. Lines of therapy are defined by clinical or radiographic progression. Patients may have received chemotherapy and immunotherapy either concurrently or sequentially in either order. Patient must have received at least 2 prior doses of checkpoint inhibitor therapy in an every 2, 3, or 4 week schedule. No submission of molecular testing is required and patients may be registered for Step 0 then proceed directly to Step 1 screening.  OR  Patients with tumors with known molecular alterations in ROS1, MET, and RETmust have progressed radiographically (per local investigator clinical assessment) on atleast one line of prior chemotherapy or targeted therapy, but there is no limit on number of prior number of therapies. Reciept of prior immunotherapy is allowed but not required.
7. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (in the opinion of the treating physician) are eligible for this trial.
8. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
9. Patients with new or progressive brain metastases (active brain metastases) are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of study treatment.