Pirfenidone Combined With Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC

This study will be conducted in two phases: 1) a Phase I dose escalation study with a
Standard 3+3 design to determine the recommended Phase II dose and 2) a Phase Ib expansion
study to evaluate early signs of efficacy and obtain more toxicity data. The Phase I trial
will be a single center, dose-escalation study of pirfenidone combined with standard
chemotherapy in the treatment of advanced/metastatic NSCLC, followed by a Phase Ib trial to
determine early clinical efficacy [objective tumor response rate (ORR)] and toxicity data.

Inclusion Criteria:

- Histologically/cytologically documented Stage IIIB to Stage IV unresectable non-small
cell lung cancer (either squamous cell carcinoma or non-squamous cell lung cancer or
mixed histology; epidermal growth factor (EGFR) or ALK mutation excluded unless
previously treated with a TKI). Patients with adenocarcinoma must have been tested for
EGFR and ALK mutations.

- At least one measurable tumor lesion as defined by Response Evaluation Criteria In
Solid Tumors (RECIST) v1.1.

- 18 years of age and older.

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

- Participants should be chemotherapy naïve in the Stage IV NSCLC setting, with the
exception of chemotherapy for neoadjuvant or adjuvant treatment that completed at
least 6 months before the study treatment.

- Participants' blood test must meet the following requirements: Absolute neutrophil
count (ANC) ≥ 1.5 x 10^9/L; Platelets ≥ 100 x 10^9/L; Hemoglobin level ≥ 9 g/dL.

- Clinical biochemistry examination must meet the following requirements: Alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x upper limit of
normal (ULN) or ≤ 5 X ULN for patients with liver metastases; Serum creatinine ≤ 1.5 x
ULN or estimated GFR ≥ 50 mL/min/m^2; Total bilirubin ≤ 1.5 x ULN; Urine pregnancy
test is negative for women of childbearing potential, within 14 days before study
treatment.

- Estimated life expectancy of at least 6 months.

- May have received prior immunotherapy.

- Have archived tissue available or be willing to undergo a fresh biopsy during
screening, if deemed feasible by the investigator/study PI. If neither available, the
patients enrollment must be reviewed and approved by the PI.

- Voluntarily participate in the clinical trial, understanding they may withdraw
participation at any time.

- Able to understand and provide written informed consent prior to trial participation.

Exclusion Criteria:

- Are currently undergoing other anti-tumor therapies or have concurrent active cancer.

- Patients who were enrolled into any other treatment clinical trial and received
treatment on that trial within 4 weeks of study treatment.

- Any clinical laboratory findings give reasonable suspicion of a disease or condition
that contraindicates the use of any study medication or render the subject at high
risk from treatment.

- Patients with previously untreated brain metastases should be excluded. Patients with
treated and stable (>4 weeks) brain metastases may be eligible for enrollment.

- History of allergic reactions to carboplatin or paclitaxel.

- Have had immunotherapy or radiotherapy within 4 weeks prior to study treatment or
those who have not recovered from adverse events due to agents administered more than
4 weeks prior to study treatment. Prior history of palliative radiation for
symptomatic bony or brain metastases is permissible.

- Are receiving any other investigational agents.

- Patients with known ROS1 mutations who have not received prior targeted therapy.

- Alcohol or drug dependence.

- Uncontrolled coagulopathy.

- Uncontrolled hyper- or hypothyroidism.

- Known hypersensitivity to pirfenidone, carboplatin, pemetrexed or paclitaxel.

- Pre-existing peripheral neuropathy of Grade II or higher.

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

- Patients receiving any medications or substances that are moderate to strong
inhibitors CYP1A2 are ineligible.

- Pregnant women are excluded from this study. Women of child-bearing potential and men
must agree to use adequate contraception prior to study entry and for the duration of
study participation. Should a woman become pregnant or suspect she is pregnant while
she or her partner is participating in this study, she should inform her treating
physician immediately. Men treated or enrolled on this protocol must also agree to use
adequate contraception prior to the study, for the duration of study participation,
and 4 months after completion of study drug administration.