Open-Label, Global, Multicenter, Randomized, Phase 3 Study of Sacituzumab Govitecan Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy

Patients must meet all of the following inclusion criteria at screening/Day *1
to be eligible for participation in this study (no waivers for patient
eligibility will be offered or permitted):
1) Female or male patients, 18 years of age or older, able to understand and
give written informed consent
2) Life expectancy of 3 months or more
3) Pathologically documented NSCLC with documented evidence of Stage 4 NSCLC
disease at the time of enrollment (based on the American Joint Committee on
Cancer, Eighth Edition).
4) EGFR, ALK, and PD-L1 results are required prior to enrollment (see Section
6.3.10). Resulting for other actionable genomic alterations is recommended and
to be performed as per local standard of care and availability of targeted
treatment. For patients with squamous cell carcinoma, EGFR and ALK testing is
optional.
5) Must have progressed after platinum-based chemotherapy in combination with
anti-PD-1/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1
antibody (in either order) sequentially.
• Note: Includes patients who received prior platinum based chemoradiotherapy
(with or without maintenance anti PD1/PD L1 antibody) for Stage 3 disease. To
be considered to have progressed during or after prior treatment with
platinum-based chemotherapy, patients should have either received prior
platinum-based chemotherapy in the recurrent/metastatic setting or have
experienced disease progression within 6 months of last dose of platinum-based
chemotherapy administered as part of concurrent chemoradiation for Stage 3
disease or as neoadjuvant or adjuvant therapy. To be considered to have
progressed during or after prior treatment with an anti-PD-1/PD-L1 antibody,
patients should have either received this therapy in the recurrent/metastatic
setting or have experienced disease progression during *maintenance* treatment
following concurrent chemoradiation for Stage 3 disease.
a) No additional treatments are allowed in the recurrent/metastatic setting for
patients with no actionable genomic alterations.
b) Patients with EGFR, ALK, or any other known actionable genomic alterations
must have also received treatment with at least 1 locally approved and
available TKI appropriate to the genomic alteration (see Appendix 8).
c) Documented radiographic disease progression while on or after receiving the
most recent treatment regimen for advanced or metastatic NSCLC.
6) Measurable disease based on computed tomography (CT) or magnetic resonance
imaging (MRI) as assessed by the investigator in accordance with per RECIST
Version 1.1. Tumor lesions situated in a previously irradiated area are
considered measurable if progression has been demonstrated in such lesions.
Historical images within 28 days of the screening visit may be accepted as a
screening image if deemed acceptable in the opinion of the investigator.
7) Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
(Appendix 5) before randomization.
8) Adequate hematologic counts without transfusional or growth factor support
within 2 weeks of study drug initiation (hemoglobin >= 9 g/dL, absolute
neutrophil count >= 1500/mm3, and platelets >= 100,000/µL).
9) Adequate hepatic function (bilirubin <= 1.5 upper limit of normal [ULN],
aspartate aminotransferase and alanine aminotransferase <= 2.5xULN or <= 5xULN if
known liver metastases, and serum albumin > 3 g/dL).
• Note: The investigator should follow local practice guidelines and/or the
docetaxel label approved in the country of drug administration for assessing
eligibility of patients for the study.
10) Creatinine clearance of at least 30 mL/min as assessed by the
Cockcroft-Gault equation {Cockcroft 1976}.
11) Male patients and female patients of childbearing potential who engage in
heterosexual intercourse must agree to use protocol-specified method(s) of
contraception as described in Appendix 3.

Patients who meet any of the following exclusion criteria at screening/Day *1
are not eligible to be enrolled in this study (no waivers for patient
eligibility will be offered or permitted):
1) Mixed small-cell lung cancer and NSCLC histology.
2) Positive serum pregnancy test (Appendix 3) or women who are lactating.
3) Known hypersensitivity to the study drugs, their metabolites, or formulation
excipients.
4) Requirement for ongoing therapy with or prior use of any prohibited
medications for SG and docetaxel as per Sections 5.6.1 and 5.11, respectively.
5) Received a prior anticancer biologic agent within 4 weeks prior to
enrollment or have received prior chemotherapy, targeted small molecule
therapy, or radiation therapy within 2 weeks prior to enrollment and have not
recovered (ie, > Grade 2 is considered not recovered) from AEs at the time of
study entry. Patients participating in observational studies are eligible.
6) Have not recovered (ie, > Grade 2 is considered not recovered) from AEs due
to a previously administered agent.
• Note: Patients with any grade alopecia are an exception to this criterion and
will qualify for the study.
• Note: If patients received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
study drug.
7) Previously received treatment with any of the following:
a) Topoisomerase 1 inhibitors. Any agent including an ADC containing a
chemotherapeutic agent targeting topoisomerase 1
b) Trop-2-targeted therapy
c) Docetaxel as monotherapy or in combination with other agents
8) Active second malignancy
• Note: Patients with a history of malignancy that have been completely
treated, with no evidence of active cancer for 3 years prior to enrollment, or
patients with surgically cured tumors with low risk of recurrence (eg,
nonmelanoma skin cancer, histologically confirmed complete excision of
carcinoma in situ, or similar) are allowed to enroll.
9) NSCLC that is eligible for definitive local therapy alone.
10) Clinically severe pulmonary compromise resulting from intercurrent
pulmonary illnesses including, but not limited to, any underlying pulmonary
disorder (ie, pulmonary emboli within 3 months of enrollment, severe asthma,
severe chronic obstructive pulmonary disease, restrictive lung disease, pleural
effusion, etc); any autoimmune, connective tissue, or inflammatory disorders
with pulmonary involvement (ie, rheumatoid arthritis, Sjogren syndrome,
sarcoidosis, etc); or prior pneumonectomy.
11) Known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate
provided they have stable CNS disease for at least 4 weeks prior to enrollment
and all neurologic symptoms have returned to baseline, have no evidence of new
or enlarging brain metastases, and are taking 10 mg/day or less of prednisone
or its equivalent. All patients with carcinomatous meningitis are excluded
regardless of clinical stability.
12) Met any of the following criteria for cardiac disease:
a) Myocardial infarction or unstable angina pectoris within 6 months of
enrollment.
b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or
ventricular fibrillation), high grade atrioventricular block, or other cardiac
arrhythmias requiring antiarrhythmic medications (except for atrial
fibrillation that is well controlled with antiarrhythmic medication); history
of QT interval prolongation.
c) New York Heart Association Class III or greater congestive heart failure or
left ventricular ejection fraction of less than 40%.
13) Active chronic inflammatory bowel disease (ulcerative colitis, Crohn*s
disease) or gastrointestinal perforation within 6 months of enrollment.
14) Active serious infection requiring antibiotics.
15) Positive HIV 1 or HIV-2 antibody with detectable viral load OR taking
medications that may interfere with SN 38 metabolism.
16) Positive for hepatitis B surface antigen. Patients who test positive for
hepatitis B core antibody will require hepatitis B virus DNA by quantitative
polymerase chain reaction for confirmation of active disease.
17) Positive hepatitis C antibody and detectable hepatitis C viral load.
18) Other concurrent medical or psychiatric conditions that, in the
investigator*s opinion, may be likely to confound study interpretation or
prevent completion of study procedures and follow up examinations.