CPI-613 and Docetaxel in Treating Patients With Stage IIIB or IV Non-small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To determine the maximum tolerate dose (MTD) of CPI-613 when used in combination with
docetaxel therapy in advanced stage non-small cell lung cancer (NSCLC). (Phase1) II. To
evaluate the response rate in patients receiving CPI-613 in combination with docetaxel
therapy. (Phase 2)

SECONDARY OBJECTIVES:

I. To determine the safety of CPI-613 addition to docetaxel therapy. II. To determine the
progression-free survival with CPI-613 in combination with docetaxel therapy at 27 weeks.

III. To determine the median progression-free survival with CPI-613 in combination with
docetaxel therapy.

OUTLINE: This is a phase I, dose-escalation study of CPI-613 followed by a phase II study.

Patients receive CPI-613 intravenously (IV) over 2 hours on days 1 and 3, and docetaxel IV on
day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients that achieve stable disease after 6 courses
then receive CPI-613 alone on days 1and 3. Courses repeat every 21 days for up to 2 years in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then
periodically for 2 years.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed stage IIIB or IV NSCLC
with radiographic proof of measurable disease per Response Evaluation Criteria in
Solid Tumors (RECIST) version (v)1.1 criteria

- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

- Life expectancy of >= 3 months

- Patients must have received previous systemic therapy to include: a regimen of
chemotherapy, immunotherapy including anti-PDL or anti-PD-L1 therapies, combined
chemotherapy and immunotherapy, provided treatment was discontinued >= 2 weeks prior
to initiation of treatment on the present protocol

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])
within institutional upper limit of normal

- International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN)

- Prothrombin time (PT) =< 1.5 x ULN

- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN or within therapeutic range
if receiving anticoagulant therapy OR

- Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above
institutional normal

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study through 30 days after the last dose of study medication; should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately

- Ability to understand and the willingness to sign an Institutional Review Board
(IRB)-approved informed consent document (either directly or via a legally authorized
representative)

Exclusion Criteria:

- Patients who have had immunotherapy or tyrosine kinase inhibitor (TKI) therapy within
two weeks prior to entering the study

- Radiotherapy or prior systemic chemotherapy within 2 weeks

- Patients who have been treated with more than one chemotherapy regimen, immunotherapy
regimen or chemotherapy/immunotherapy regimen for metastatic non-small cell lung
cancer

- Adverse events resulting from previous therapies have not recovered to grade 1 or less

- Patients may not be receiving any other investigational agents

- Patients with untreated, symptomatic brain metastases should be excluded from this
clinical trial (patients with asymptomatic brain metastases amenable to treatment with
Gamma Knife radiosurgery ["GKRS"] are eligible and may receive GKRS while on protocol)

- Lactating females

- Patients with EGFR, ALK or ROS-1 mutations who are eligible for treatment with a TKI
and who have not received such treatment

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to CPI-613 or docetaxel

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with CPI-613

- Any condition that may, in the opinion of the investigator, compromise the safety of
the patient