Study of Carotuximab (TRC105) Plus Nivolumab in Patients With Metastatic NSCLC
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Carotuximab (TRC105); OPDIVO
Intervention description: Anti Endoglin Antibody; Programmed Death Receptor-1
Intervention MeSH terms: Nivolumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a multi-center, open-label, nonrandomized, dose-escalation, Phase 1b study of
      carotuximab in combination with standard dose nivolumab in patients with NSCLC that has
      progressed on or after platinum-based chemotherapy or PD-1/PD-L1 checkpoint inhibition, as a
      single agent or with chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed metastatic non-small cell lung cancer (NSCLC) with disease
             recurrence or progression during or after prior platinum-containing doublet
             chemotherapy regimen

          2. Histologically confirmed metastatic non-small cell lung cancer (NSCLC) that has
             relapsed following prior PD-1/PD-L1 checkpoint inhibitor therapy without Grade 3
             immune-related toxicity, which may or may not have included concurrent chemotherapy.
             Relapse following prior PD-1 checkpoint therapy is defined as confirmed progressive
             disease following stable disease or better (e.g., iSD, iPR, iCR) on at least 1 tumor
             assessment.

          3. Patients with an active oncogenic driver (e.g., epidermal growth factor [EGFR],
             activin-receptor-like kinase 1 [ALK1], or the proto-oncogene tyrosine-protein kinase
             ROS-1) must have progressed on or after a US Food and Drug Administration
             (FDA)-approved therapy for that aberration

          4. Patients who received adjuvant or neoadjuvant platinum-doublet chemotherapy (after
             surgery and/or radiation therapy) and developed recurrent or metastatic disease within
             6 months of completing therapy are eligible.

          5. Patients with recurrent disease > 6 months after adjuvant or neoadjuvant
             platinum-based chemotherapy, who also subsequently progressed during or after a
             platinum- doublet regimen given to treat the recurrence, are eligible.

          6. Formalin fixed, paraffin-embedded (FFPE) tumor tissue block that permits the
             preparation of 20 unstained slides of tumor sample (archival) - Biopsy must be
             excisional, incisional, or core. Needle aspiration is insufficient. In cases where
             archival tumor tissue is unavailable, tumor biopsy will be required prior to treatment
             initiation.

          7. Programmed death ligand 1 (PD-L1) determination by validated immunohistochemistry
             assay

          8. Measurable disease by iRECIST

          9. Age ≥ 18 years

         10. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

         11. Resolution of all acute adverse events resulting from prior cancer therapies to
             National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
             Grade ≤ 1 or baseline (except alopecia or neuropathy)

         12. Adequate organ function

         13. Willingness and ability to consent for self to participate in study

         14. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other study procedures

        Exclusion Criteria:

          1. Autoimmune disease requiring treatment within the past twelve months.

          2. Condition requiring systemic treatment with either corticosteroids

          3. History or active interstitial lung disease

          4. Prior therapy with T-cell therapy, including an immune checkpoint inhibitor. Patients
             who received prior immune checkpoint inhibitor therapy are allowed in Expansion Cohort
             2 in the absence of recurrent grade 2 (except skin, endocrine and constitutional
             symptoms), or ≥ 3 immune-related toxicity).

          5. Prior treatment with carotuximab

          6. Current treatment on another therapeutic clinical trial

          7. Receipt of systemic anticancer therapy, including investigational agents, within 28
             days prior to study treatment (Note: If anticancer therapy was given within 28 days
             prior to starting study treatment, patients are not excluded if ≥ 5 times the
             elimination half-life of the drug has elapsed.)

          8. Major surgical procedure or significant traumatic injury within 4 weeks prior to study
             treatment, and must have fully recovered from any such procedure; and no date of
             surgery (if applicable) or anticipated need for a major surgical procedure planned
             within the next 6 months

          9. Chest radiotherapy ≤ 28 days, wide field radiotherapy ≤ 28 days (defined as > 50% of
             volume of pelvic bones or equivalent), or limited field radiation for palliation ≤ 14
             days prior to study treatment - Such patients must have recovered adequately from any
             side effects of such therapy.

         10. Hypertension defined as blood pressure (BP) systolic > 150 or diastolic > 90 mm Hg
             (Note: Initiation or adjustment of antihypertensive medication prior to study entry is
             allowed provided that the average of 3 BP readings prior to study treatment is ≤150/90
             mm Hg.)

         11. Ascites or pericardial effusion that required intervention within 3 months prior to
             study treatment

         12. History of brain involvement with cancer, spinal cord compression, or carcinomatous
             meningitis, or new evidence of brain or leptomeningeal disease

         13. Angina, myocardial infarction (MI), symptomatic congestive heart failure,
             cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary
             embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery
             bypass grafting (CABG) within 6 months prior to study treatment

         14. Deep venous thrombosis within 6 months prior to study treatment, unless the patient is
             anti-coagulated without the use of warfarin for ≥2 weeks prior to study treatment; in
             this situation, low molecular weight heparin is preferred

         15. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g.,
             hereditary hemorrhagic telangiectasia)

         16. Thrombolytic use (except to maintain IV catheters) within 10 days prior study
             treatment

         17. Known active viral or nonviral hepatitis or cirrhosis

         18. Any active infection requiring systemic treatment

         19. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months
             prior to study treatment

         20. History of peptic ulcer within the past 3 months prior to study treatment, unless
             treated for the condition and complete resolution has been documented by
             esophagogastroduodenoscopy (EGD) within 28 days prior to study treatment

         21. History of gastrointestinal perforation or fistula in the 6 months prior to study
             treatment, or while previously on antiangiogenic therapy, unless underlying risk has
             been resolved (e.g., through surgical resection or repair)

         22. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
             related illness

         23. Pregnancy or breastfeeding - Female patients must be surgically sterile (i.e., ≥6
             weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal
             ligation) or be postmenopausal, or must agree to use effective contraception during
             the study and for 3 months following last dose of carotuximab. All female patients of
             reproductive potential must have a negative pregnancy test (serum or urine) within 7
             days prior to study treatment. Male patients must be surgically sterile or must agree
             to use effective contraception during the study and for at least 180 days following
             last dose of study drug (carotuximab or nivolumab, whichever occurs later).

         24. Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or may
             interfere with the interpretation of study results and, in the judgment of the
             Investigator, would make the patient inappropriate for this study.