The primary objective of the study is to compare overall survival of participants randomized to receiving custirsen in combination with docetaxel with participants randomized to receive docetaxel alone.

Inclusion Criteria:

1. Patients must have a histologically or cytologically confirmed, unresectable, advanced or metastatic (Stage IV per American Joint Committee on Cancer 7th edition Tumor size, lymph Nodes affected, Metastases staging) non-small cell lung cancer (NSCLC).

2. Males or females ≥ 18 years of age at screening.

3. Life expectancy of > 12 weeks from screening, according to the investigator's assessment.

4. Patients must have received one prior line of platinum-based systemic anticancer therapy for advanced or metastatic NSCLC. Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued at the end of a treatment regimen.

5. Patients must have documented radiological disease progression either during or after the first-line therapy.

6. Patients must have at least one measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.

8. Have adequate values, bone marrow, renal and liver functions at screening as defined below:

   • Absolute neutrophil count ≥ 1.5 x 10^9/L
   • Platelet count ≥ 100 x 10^9/L
   • Hemoglobin ≥ 9 g/dL
   • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
   • Total Bilirubin ≤ 1.0 x ULN (unless elevated secondary to benign conditions such as Gilbert's disease)
   • Aspartate aminotransferase and alanine aminotransferase ≤ 1.5 x ULN.

9. Resolution of any toxic effects of prior therapy to Grade ≤1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (exception of alopecia and ≤ Grade 2 peripheral neuropathy).

10. Females of child-bearing potential must have negative serum pregnancy test within 72 hours before randomization.

11. Women of child-bearing potential will practice a highly effective method of birth control during and for 3 months after the chemotherapy/custirsen last dose. Men of reproductive potential who are not surgically sterile must agree to abstain from sexual activity or use medically accepted and highly effective method of contraception during and for 6 months after the chemotherapy/custirsen last dose.

12. Patients must be willing and able to give written informed consent prior to any protocol-specific procedures being performed and comply with the protocol requirements for the duration of the study.

Exclusion Criteria:

1. Patients treated with any systemic anti-cancer therapy for NSCLC within 21 days prior to randomization (6 weeks for bevacizumab).
2. Radiotherapy ≤ 2 weeks prior to randomization. Patients must have recovered from all radiotherapy-related toxicities.
3. Major surgical procedure within 4 weeks prior to randomization. Patient must have recovered from all surgery-related complications.
4. Patients with known central nervous system (CNS) metastases (patients with any clinical signs of CNS metastases must have a computed tomography or magnetic resonance imaging of the brain to rule out CNS metastases in order to be eligible for participation in the study). Patients who have had brain metastases treated with radiotherapy or surgically removed with no residual disease confirmed by imaging; patients should be clinically stable and off corticosteroid treatment at least 3 weeks prior to randomization).
5. Patients with current diagnosis or a history of another active primary malignancy (except in situ carcinoma of the cervix, adequately treated non-melanomatous skin cancers, clinically localized prostate cancer, superficial bladder cancer or other malignancy treated at least 5 years previously with no evidence of recurrence).
6. Severe or unstable medical conditions such as heart failure, ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an ongoing cardiac arrhythmia requiring medication (≥ Grade 2, according to NCI CTCAE v4.0) or any other significant or unstable concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy.
7. A history of events such as myocardial infarction, cerebrovascular accident or acute hepatitis within 3 months of randomization or treatment of a major active infection within one month of randomization, or any other significant event that in the opinion of the Investigator would preclude protocol therapy.
8. Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.
9. Female patients who are breastfeeding.
10. Patients previously treated with docetaxel for NSCLC or with known severe hypersensitivity to taxane therapies.
11. Patients with known and documented epidermal growth factor receptor (EGFR) mutation who have not received an EGFR inhibitor.