A Study of Vantictumab (OMP-18R5) in Combination With Docetaxel in Patients With Previously Treated NSCLC

A Phase 1b Study of Vantictumab (OMP-18R5) in Combination With Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of vantictumab when combined with docetaxel.

Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been determined, up to 10 patients may be enrolled in the cohort-expansion phase to better characterize the safety, tolerability and PK of vantictumab combined with docetaxel. Up to approximately 34 patients may be enrolled into the study.

Inclusion Criteria:

• Signed Informed Consent Form
• Age ≥18 years
• Histologically documented recurrent or advanced (Stage IV) NSCLC
• Eastern CooperativeOncology Group (ECOG) performance status of 0 or 1
• All acute treatmentrelated toxicity from prior therapy must have resolved to Grade ≤ 1 prior to study entry
• Adequate hematologic and end-organ function
• Evaluable or measurable disease per RECIST v1.1
• For women of childbearing potential and men with partners of childbearing potential, agreement to use two effective forms of contraception

Exclusion Criteria:

• Prior treatment with docetaxel for recurrent or advanced NSCLC

• More than two regimens of systemic cytotoxic chemotherapy for recurrent or advanced NSCLC

• Treatment with any anti-cancer therapy within 3 weeks prior to initiation of study treatment

• Known hypersensitivity to any component of study treatments

• Grade ≥ 2 sensory neuropathy

• Uncontrolled seizure disorder or active neurologic disease

• Untreated brain metastases

• Leptomeningeal disease as a manifestation of cancer

• Active infection requiring antibiotics

• Bisphosphonate therapy for symptomatic hypercalcemia

• Known history of clinically significant liver disease, including active viral hepatitis and cirrhosis

• Significant intercurrent illness including, but not limited to, unstable angina pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements

• Pregnancy, lactation, or breastfeeding

• Known HIV infection

• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

• Concurrent use of therapeutic warfarin

• New York Heart Association Classification III or IV (see Appendix E)

• Known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study

• Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan

• Bone metastases and one of the following:

  • Prior history of a pathologic fracture
  • Lytic lesion requiring an impending orthopedic intervention
  • Lack of treatment with a bisphosphonate or denosumab

• Treatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone), and Avandia® (rosiglitzone)

• Active treatment with an oral or IV glucocortocoid for ≥4 weeks at a daily dose equivalent to or greater than 7.5 mg of oral prednisone

• Fasting β-CTX of >1000 pg/mL

• Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia