Lurbinectedin with Osimertinib for the Treatment of Transformed Small Cell Lung Cancer

Inclusion Criteria

• ≥ 18 years old at the time of informed consent
• Ability to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
• Must have a histologically or cytologically confirmed transformation to small cell lung carcinoma/cancer
• Must have an initial diagnosis of EGFR altered (EGFR-mutated) non-small cell lung cancer and received EGFR targeted therapy (tyrosine kinase inhibitor [TKI]) osimertinib, and does not demonstrate evidence of acquired molecular underpinnings (i.e., presence of a MET amplification ≥ 6 copies or EGFR C797S) resulting in progression on osimertinib, aside from histologic transformation to small cell lung cancer. Interruptions of osimertinib prior to enrollment on study is permitted. * Note: Tissue specimens from archival tissue are encouraged but not required for enrollment
• Patients who have received platinum (cisplatin or carboplatin)/etoposide after histologic transformation are permitted on study. Receipt of last cycle of therapy should be at least 3 weeks prior to initiation of treatment on study. Last exposure to immunotherapy such as anti-PD-L1 should be at least four weeks from treatment to initiation of treatment on study. Patients who decline to receive platinum/etoposide after SCLC transformation, for personal preferences or considered medical ineligible for this regimen, may be considered for this study, subject to investigator discretion
• Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (on baseline testing within 21 days of enrollment)
• Platelet count (Plt) ≥ 100 x 10^9/L (on baseline testing within 21 days of enrollment)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (on baseline testing within 21 days of enrollment); for patients with suspected/documented Gilbert’s syndrome, total bilirubin ≤ 3 x ULN
• Aspartate aminotransferase (AST) ≤ 3 x ULN (on baseline testing within 21 days of enrollment)
• Alanine aminotransferase (ALT) ≤ 3 x ULN (on baseline testing within 21 days of enrollment)
• Creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR, calculated per institutional standards) should be > 30 mL/min (on baseline testing within 21 days of enrollment)
• Women of childbearing potential must have a negative pregnancy test within 21 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria: * Has achieved menarche at some point; or * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Women of childbearing potential and men with any partners of child-bearing potential must agree to use 2 forms of effective contraception throughout the study and for 6 months after the last study treatment. * Note: Acceptable methods of birth control include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections)
• Male subjects must agree to refrain from donating sperm during the study and for 6 months after the last study treatment. Female subjects must agree to refrain from donating eggs during the study and for 6 months after the last study treatment

Exclusion Criteria

• Patients who have tumors harboring EGFR exon 20 insertion alterations, EGFR C797S, or known mechanisms of resistance to osimertinib (i.e., MET amplification) aside from histologic transformation to SCLC
• Patients who are pregnant (treatment can cause fetal harm) and/or breastfeeding
• Symptomatic or unstable brain metastases, requiring > 2 mg dexamethasone orally daily, or received palliative radiation to the central nervous system (CNS) within 2 weeks of enrollment
• Patients with known history of interstitial lung disease (ILD) or pneumonitis (> grade 1) or ILD/pneumonitis (> grade 1) related to antineoplastic drug treatment
• Prior history of documented Stephen Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), erythema multiforme major (EMM), or aplastic anemia on osimertinib
• History of congenital long corrected QT interval (QTc) syndrome or mean resting QTc > 500 msec at screening with two replicated electrocardiograms (EKGs) at baseline screening for the study
• History of ongoing unstable or uncontrolled cardiac conditions, including documented cardiomyopathy or symptomatic congestive heart failure (defined as New York Heart Association [NYHA] class III or IV)
• Prior history of documented severe allergic or anaphylactic reaction to osimertinib
• Prior history of documented aplastic anemia with osimertinib
• Prior history of documented allergic or anaphylactic reactions to inactive ingredients of lurbinectedin, including sucrose, lactic acid, and sodium hydroxide