Open-Label, Biomarker-Integrated Umbrella Trial for First-Line Treatment of Extensive-stage Small Cell Lung Cancer

NCT07172412 | Not Yet Recruiting Phase 2

• 1 other identifier: BUTTONS-001
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Extensive Stage Lung Small Cell Cancer

Outcome Measures

Primary Outcomes (3)

• PFS

  through study completion, an average of 1 year

• ORR

  through study completion, an average of 1 year

• OS

  through study completion, an average of 1 year

Study Arms (3)

Anlotinib TEAM

EXPERIMENTAL

Anlotinib+SOC therapy

Drug: Anlotinib; Drug: Etoposide + Cisplatin/Carboplatin; Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab

DLL3 TEAM

EXPERIMENTAL

DLL3 CAR-NK cell+SOC therapy

Biological: DLL3 CAR-NK cells; Drug: Etoposide + Cisplatin/Carboplatin; Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab

XPO1 TEAM

EXPERIMENTAL

Selinexor+SOC therapy

Drug: Selinexor; Drug: Etoposide + Cisplatin/Carboplatin; Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab

Interventions

Selinexor DRUG

Selinexor 60 mg biw q21d

XPO1 TEAM

Anlotinib DRUG

Anlotinib 12mg d1-14 qd PO

Anlotinib TEAM

DLL3 CAR-NK cells BIOLOGICAL

1.0×10\^9 DLL3-CAR-NK+ cells d5 q6w

DLL3 TEAM

Etoposide + Cisplatin/Carboplatin DRUG

Etoposide 100mg/m\^2 d1-3+ cisplatin 75mg/m\^2 d1-3 or Carboplatin AUC5

Anlotinib TEAM; DLL3 TEAM; XPO1 TEAM

Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab DRUG

Use immunotherapy according to the standard immunotherapy-combined-chemotherapy protocol.

Anlotinib TEAM; DLL3 TEAM; XPO1 TEAM

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The diagnosis of SCLC is confirmed by histology or cytology, and according to VALSG and AJCC9, the imaging diagnosis is extensive stage.
• Patients who have not previously received systemic therapy for advanced or metastatic disease, or patients who have relapsed after concurrent chemo-radiotherapy during the localized stage.
• The expected survival time is not less than 12 weeks.
• According to RECIST V1.1, there is at least one measurable lesion that has not undergone radiation therapy.
• The Eastern Cooperative Oncology Group (ECOG) physical condition score is evaluated as 0 or 1.
• When screening, there is sufficient bone marrow reserve, and no blood transfusion or hematopoietic stimulating factor treatment has been received 10 days before the test. The definition is as follows: absolute neutrophil counts (ANC) ≥ 1.5×109/L, platelet (PLT) ≥ 100×109/L and hemoglobin (HGB) ≥ 90g/L.
• Appropriate organ function during screening, meeting the following criteria: aspartate aminotransferase (AST) ≤ 2.5×ULN (with liver metastasis ≤ 5×ULN); alanine aminotransferase (ALT) ≤ 2.5ULN (with liver metastasis ≤ 5ULN); total serum bilirubin ≤ 1.5×ULN (with tumor infiltration ≤ 3×ULN); serum creatinine (Scr) ≤ 1.5×ULN, or creatinine clearance rate ≥ 60mL/min; international normalized ratio (INR) ≤ 1.5×ULN, and activated partial thromboplastin time (APTT) ≤ 1.5×ULN; the urine pregnancy test for women of childbearing age needs to be negative, and any male and female patients with fertility must agree to use effective contraceptive methods throughout the entire study process and for at least 1 year after treatment.

You may not qualify if:

• During screening, patients with symptomatic central nervous system (CNS) metastasis (asymptomatic CNS metastasis, or asymptomatic and stable condition after local treatment for 4 weeks can be enrolled).
• Individuals with a history of central nervous system diseases before screening, such as epilepsy, cerebral ischemia/bleeding, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, mental illness, or any autoimmune disease associated with central nervous system involvement.
• Received chemotherapy, radiation therapy, immunotherapy, targeted therapy, biological therapy, endocrine therapy within 4 weeks of screening, and was evaluated by the researcher as not suitable for enrollment.
• The adverse reactions of previous anti-tumor treatments have not yet recovered to level 1 (CTCAE5.0), except for toxicity that the researchers have determined to have no safety risk, such as hair loss and level 2 peripheral neurotoxicity.
• Those who discontinue systemic hormone therapy for less than 72 hours before the first administration, but are allowed to use physiological replacement doses of hormones (such as prednisone \< 10mg/d or equivalent).
• Received organ/tissue transplantation before screening.
• Prior to screening, it was known that the patient had active systemic autoimmune diseases and was currently undergoing treatment.
• Those who meet any of the following conditions during screening: hepatitis B surface antigen (HBsAg) is positive, and the copy number of HBV DNA is greater than the measurable lower limit; hepatitis C antibody (HCV Ab) is positive; treponema pallidum antibody (TP-Ab) is positive; HIV antibody is positive; The copy numbers of EBV-DNA and CMV-DNA are higher than the measurable lower limit.
• Within 2 years prior to screening or currently suffering from other malignant tumors.
• When screening, the heart meets any of the following conditions: New York Heart Association (NYHA) ≥ Level II, Left Ventricular Ejection Fraction (LVEF) ≤ 50% (ECHO); Hypertension (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg) or pulmonary hypertension that has not been controlled after standardized treatment; Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first administration; valvular disease with clinical significance; There are serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias that require clinical intervention, II-III degree atrioventricular block, etc.
• Patients with tumor involving the atrium or ventricle during screening.
• When screening, there are clinical emergencies that require urgent treatment due to tumor obstruction or compression (such as intestinal obstruction or vascular compression).
• Individuals with active bleeding during screening.
• Those with a history of deep vein thrombosis or pulmonary embolism within 6 months before screening.
• Individuals who have received live vaccines within 6 weeks before screening.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 300060

Tianjin, Tianjin Municipality, China

Location

Related Publications (3)

• Liu Q, Zhang J, Guo C, Wang M, Wang C, Yan Y, Sun L, Wang D, Zhang L, Yu H, Hou L, Wu C, Zhu Y, Jiang G, Zhu H, Zhou Y, Fang S, Zhang T, Hu L, Li J, Liu Y, Zhang H, Zhang B, Ding L, Robles AI, Rodriguez H, Gao D, Ji H, Zhou H, Zhang P. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell. 2024 Jan 4;187(1):184-203.e28. doi: 10.1016/j.cell.2023.12.004.

  PMID: 38181741 BACKGROUND

• Wang J, Sun T, Meng Z, Wang L, Li M, Chen J, Qin T, Yu J, Zhang M, Bie Z, Dong Z, Jiang X, Lin L, Zhang C, Liu Z, Jiang R, Yang G, Li L, Zhang Y, Huang D. XPO1 inhibition synergizes with PARP1 inhibition in small cell lung cancer by targeting nuclear transport of FOXO3a. Cancer Lett. 2021 Apr 10;503:197-212. doi: 10.1016/j.canlet.2021.01.008. Epub 2021 Jan 23.

  PMID: 33493586 BACKGROUND

• Qin T, Wang J, Wang J, Du Q, Wang L, Liu H, Liu W, Li X, Jiang Y, Xu Q, Yu J, Liu H, Wang T, Li M, Huang D. Nuclear to Cytoplasmic Transport Is a Druggable Dependency in HDAC7-driven Small Cell Lung Cancer. Adv Sci (Weinh). 2025 Apr;12(14):e2413445. doi: 10.1002/advs.202413445. Epub 2025 Jan 30.

  PMID: 39887933 BACKGROUND

MeSH Terms

Interventions

selinexor; anlotinib; Etoposide; Cisplatin; Carboplatin; tislelizumab; atezolizumab

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Central Study Contacts

Dingzhi Huang, M.D

CONTACT

+86-22-23340123-3210; dingzhih72@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 15, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available within 6 months of study completion

Locations

CN (1)