Extensive Stage Lung Small Cell Cancer

Eligible untreated participants with Extensive Stage Small Cell Lung Cancer (ES-SCLC) who are ≥ 18 years of age will be randomized to receive ivonescimab 10 milligrams per kilogram (mg/kg) or ivonescimab 20 mg/kg in combination with carboplatin and etoposide. Ivonescimab is a type of drug called a bispecific antibody. Antibodies are proteins that specifically recognize and bind to other types of proteins called antigens. Antibodies and antigens can work together to help the immune system fight cancer cells. Bispecific antibody, meaning it targets two different molecules at the same time. Ivonescimab is a new drug that may help the immune system attack cancer cells and may also block certain pathways that cancer uses to grow and spread. This dual action of ivonescimab aims to help the immune system to fight the cancer and also disrupt tumor growth by blocking blood vessel formation that tumors use to grow. Participants will receive induction with 4 cycles of ivonescimab (dose determined by randomization) with standard of care carboplatin and etoposide followed by maintenance therapy with ivonescimab at the same dose received during induction. Treatment will continue until disease progression, unacceptable toxicity or participant withdrawal. The purpose of this study is to determine what dose of ivonescimab works best in combination with carboplatin and etoposide chemotherapy in ES-SCLC. We will also examine the side effects, good and bad, associated with ivonescimab.

Eligible untreated participants with Extensive Stage Small Cell Lung Cancer (ES-SCLC) who are ≥ 18 years of age will be randomized to receive ivonescimab 10 milligrams per kilogram (mg/kg) or ivonescimab 20 mg/kg in combination with carboplatin and etoposide. Ivonescimab is a type of drug called a bispecific antibody. Antibodies are proteins that specifically recognize and bind to other types of proteins called antigens. Antibodies and antigens can work together to help the immune system fight cancer cells. Bispecific antibody, meaning it targets two different molecules at the same time. Ivonescimab is a new drug that may help the immune system attack cancer cells and may also block certain pathways that cancer uses to grow and spread. This dual action of ivonescimab aims to help the immune system to fight the cancer and also disrupt tumor growth by blocking blood vessel formation that tumors use to grow. Participants will receive induction with 4 cycles of ivonescimab (dose determined by randomization) with standard of care carboplatin and etoposide followed by maintenance therapy with ivonescimab at the same dose received during induction. Treatment will continue until disease progression, unacceptable toxicity or participant withdrawal. The purpose of this study is to determine what dose of ivonescimab works best in combination with carboplatin and etoposide chemotherapy in ES-SCLC. We will also examine the side effects, good and bad, associated with ivonescimab.

This is a single arm, multi-center clinical trial. The goal of this clinical trial is to evaluate the efficacy, safety and biomarkers of Tafolecimab combined with Sintilimab and Chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). Tafolecimab is a recombinant fully humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK-9), which can reduce low-density lipoprotein-C levels and increase the expression level of major histocompatibility complex class I (MHC-I) on tumor cells. Sintilimab is a fully humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1).

START-lung is an international, multicentre, single-arm phase II trial. Protocol treatment consists of tarlatamab administered as an intravenous infusion until disease progression according to RECIST v1.1 criteria, unacceptable toxicity, or patient decision, whichever comes first. The primary objective of the trial is to assess the clinical efficacy of tarlatamab, in terms of 12-month OS rate, in patients with ES-SCLC and ECOG PS 2 who have previously received only one line of platinum-etoposide doublet chemotherapy with immune-checkpoint inhibition and whose disease has progressed.

This is an open-label umbrella study conducted in first treatment ES-SCLC patients, employing a novel umbrella trial design (biomarker-integrated multi-arm trial with a shared ICI+chemotherapy control arm). Eligible patients were assigned to trial arms based on biomarker expression levels. Biomarker subgroups were defined as: (1) High ASCL1/NEUROD1/DLL3 expression: DLL3-CAR-NK cells combined with ICI + etoposide + carboplatin (DLL3 group); (2) Myc overexpression: XPO1 inhibitor selinexor combined with ICI + etoposide + carboplatin (XPO1 group); (3) VIM/AXL high expression group treated with anlotinib combined with ICI + etoposide + carboplatin (anlotinib group).