Study of Sacituzumab Govitecan With Atezolizumab/Durvalumab as Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer

The goal of this clinical trial is to learn if the combination of sacituzumab govetican (SG) and atezolizumab/durvalumab is effective in controlling cancer tumor growth in adults with extensive stage small cell lung cancer. These drugs are FDA approved individually in different cancers. This combination is evaluated in breast cancer and showed promising combination. The effectiveness of this treatment combination will be measured by changes in tumor size and appearance of new tumors. Participants in the trial will: * receive treatment SG and immunotherapy every 21 days for up to 2 years or until it is no longer works for the patient. * CT scans at 6weeks for first 6 cycles and then every 9-12 weeks and MRI brain every 12 weeks. * provide tissue (optional) and blood for additional testing (learn about the cancer).

Small Cell Lung Cancer (SCLC) is a high-grade neuroendocrine tumor, accounting for nearly 15% of all lung cancers. It is characterized by rapid doubling time, high vascularity, apoptotic imbalance, and early widespread hematogenous metastasis. More than two-thirds of the patients present with extensive stage and only one-third of them present with limited stage confined to the chest. Prognosis continues to be poor with a 3yr relative survival rate of 13%. Despite high response rate with platinum-based chemotherapy, the median survival is limited in patients with advanced SCLC due to early recurrence. The addition of atezolizumab to platinum doublet in the extensive stage has shown only marginal improvement in both progression free survival (PFS) (5.2 months vs 4.3 months) and median overall survival (OS) (12.3 months vs 10.3 months) Similar results were observed with the addition of Durvalumab (median OS- 12.9 months vs 10.5 months). Therefore, there is a significant need to develop strategies that can sustain the response of platinum-based chemotherapy and thus prolong PFS and OS in advanced SCLC patients. Transmembrane glycoprotein Trophoblast cell surface antigen 2 (TROP-2) is expressed at membranous and/ or cytoplasmic levels in many epithelial solid tumors including SCLC and is associated with poor prognosis. It plays an important role in carcinogenesis and tumor progression. Sacituzimab govitecan (SG) is an anti-TROP-2 antibody-drug conjugate composed of a humanized monoclonal antibody coupled with a toxic payload, SN-38, an active metabolite of irinotecan with a hydrolyzable linker. The antitumor activity/ efficacy of SG in SCLC was first noticed in first in human studies with \>30% reduction of target lesions even after progression on prior topoisomerase I inhibitor. SG was evaluated in a phase I/II dose expansion/ escalation cohort to assess safety and efficacy in relapsed and refractory SCLC following 2 median prior therapies with a primary endpoint of objective response, assessed by imaging. A dose of 10mg/kg was determined to be dose-maximized efficacy and safety. Key treatment-related adverse events reported were neutropenia (57.8%) and diarrhea (56.2%). Patients with homozygous UGT1A1 allele status had an increased risk of neutropenia. Other common side effects reported were nausea/ vomiting, abdominal pain, anorexia, constipation, fatigue, anemia, and alopecia. Overall response rates of 14% (7/50) based on ITT (intention to treat) and 17% (6/36) for patients in the 10 mg/kg dose group, with a median duration of response of 5.7 months. Stable disease is noted in 42% of patients (21/50). In an open-label, multicohort Phase 2 study (TROPiCS-03), SG was evaluated in a second-line setting in patients who progressed after chemotherapy/immunotherapy in SCLC. Among 43 patients enrolled, the overall response rate was 41.9%, with a median PFS of 4.4 months (95% CI 3.81-6.11) and a median OS of 13.6 months (95% CI 6.57-14.78). All patients h Покажи пълното описание...

Inclusion Criteria: * Participant is willing and able to give informed consent for participation in the trial. * Male or Female aged 18 years or above. * Participants must have a histologically or cytologically confirmed diagnosis of small cell lung cancer (SCLC) and extensive stage at diagnosis or locally advanced disease and unable to receive curative intent radiation. * Participants must have received at least four cycles of platinum plus etoposide and at least 2-3 cycles of atezolizumab/ Durvalumab. * No evidence of progression on restaging CT CAP following 4-6 cycles of Chemo/IO from the last dose of the chemotherapy cycle. * ECOG performance status of 0-2 * Patients must not have active uncontrolled HIV, HBV, and HCV infections. Well-controlled infections on treatment will be allowed to participate in the trial. * Patients with stable and asymptomatic brain metastasis. * Adequate organ function - bone marrow, kidney, and liver. Exclusion Criteria: * Significant renal impairment requiring dialysis or hepatic impairment with end-stage liver disease. * Participants with leptomeningeal disease. * Participants with a recent diagnosis of heart failure and acute coronary disease within 3 months. * Participants who are unable to receive immunotherapy with chemotherapy for induction will be excluded, or those immunotherapy was discontinued to manage immune-related adverse events * Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrolment. * Patients with prior exposure to anti-PD-1, anti-PD-L1, or anti-PD-L2 agents or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4) within 12 months of the study is not allowed.