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) Testing for EGFR, ALK, and PD-L1 is required. Testing for other actionable genomic alterations is recommended and to be performed as per local standard of care and availability of targeted treatment.
5) Must have progressed after platinum-based chemotherapy in combination with anti-PD-L1 antibody OR platinum-based chemotherapy and anti-PD-L1 antibody (in either order) sequentially.
* Note: Includes patients who received prior platinum-based chemoradiotherapy (with or without maintenance anti-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-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.
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.