Extensive Stage Lung Small Cell CancerPhase 2NCT07172412
Open-Label, Biomarker-Integrated Umbrella Trial for First-Line Treatment of Extensive-stage Small Cell Lung Cancer
A Phase 2 study testing Selinexor, Anlotinib and DLL3 CAR-NK cells in people with Extensive Stage Lung Small Cell Cancer, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Extensive Stage Lung Small Cell Cancer
- What is being tested?
- Selinexor, Anlotinib and DLL3 CAR-NK cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- 1 siteChina
- Study dates
- Nov 2025to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
- Individuals who have undergone major surgery or experienced significant trauma within 4 weeks prior to screening, or who require elective surgery during the trial period, have been evaluated by the researchers as unsuitable for inclusion.
- 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.
- Subjects with uncontrolled systemic bacterial, viral, or fungal infections after optimal treatment.
- Participated in other interventional clinical studies within 4 weeks before the first administration.
- Individuals with poor adherence or those who are deemed unsuitable for clinical trials by researchers due to other reasons.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 300060
Tianjin, Tianjin Municipality
Dingzhi Huang, 022-23340123-3210
About this study
Official title: An Umbrella Ib/II Phase Study Evaluating the Efficacy and Safety of First-Line Combination Therapy in the Treatment of Extensive-Stage Small Cell Lung Cancer
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).
Read the detailed description
Patients received specific targeted therapy combined with SOC treatment (etoposide 100 mg/m² on days 1-3 + carboplatin AUC5 on day 1 + immunotherapy on day 1): (1) DLL3 cohort: 1.0 × 10^9 DLL3-CAR-positive NK cells d5 q6w; (2) XPO1 cohort: Oral selinexor 60 mg biweekly q21d; (3) Anlotinib cohort: Oral anlotinib 12 mg on days 1-14, q21d.
- Conditions
- Extensive Stage Lung Small Cell Cancer
- Being tested
- Selinexor, Anlotinib, DLL3 CAR-NK cells, Etoposide + Cisplatin/Carboplatin, Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Selinexor 60 mg biw q21d
AnlotinibDrug
Anlotinib 12mg d1-14 qd PO
DLL3 CAR-NK cellsBiological
1.0×10^9 DLL3-CAR-NK+ cells d5 q6w
Etoposide + Cisplatin/CarboplatinDrug
Etoposide 100mg/m^2 d1-3+ cisplatin 75mg/m^2 d1-3 or Carboplatin AUC5
Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/SerplulimabDrug
Use immunotherapy according to the standard immunotherapy-combined-chemotherapy protocol.
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib TEAM | Experimental | Anlotinib+SOC therapy Receives: Drug: Anlotinib; Drug: Etoposide + Cisplatin/Carboplatin; Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab |
| DLL3 TEAM | Experimental | DLL3 CAR-NK cell+SOC therapy Receives: Biological: DLL3 CAR-NK cells; Drug: Etoposide + Cisplatin/Carboplatin; Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab |
| XPO1 TEAM | Experimental | Selinexor+SOC therapy Receives: Drug: Selinexor; Drug: Etoposide + Cisplatin/Carboplatin; Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Measured: through study completion, an average of 1 year
ORR
Measured: through study completion, an average of 1 year
OS
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2025
- Study startNov 2025 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Extensive Stage Lung Small Cell CancerStudies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 165 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07172412
- Sponsor's protocol ID
- BUTTONS-001
- Status last verified
- Sep 2025
- First submitted
- 8 Sep 2025
- Last updated
- 30 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 38181741Wang 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.
PubMed 33493586Qin 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.
PubMed 39887933
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Umbrella Ib/II Phase Study Evaluating the Efficacy and Safety of First-Line Combination Therapy in the Treatment of Extensive-Stage Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT07172412
- Acronym / sponsor ID
- BUTTONS-001
- Conditions
- Extensive Stage Lung Small Cell Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 165 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- Nov 2025 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 15 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Patients received specific targeted therapy combined with SOC treatment (etoposide 100 mg/m² on days 1-3 + carboplatin AUC5 on day 1 + immunotherapy on day 1): (1) DLL3 cohort: 1.0 × 10^9 DLL3-CAR-positive NK cells d5 q6w; (2) XPO1 cohort: Oral selinexor 60 mg biweekly q21d; (3) Anlotinib cohort: Oral anlotinib 12 mg on days 1-14, q21d.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Anlotinib TEAM | Experimental | Drug: Anlotinib, Drug: Etoposide + Cisplatin/Carboplatin, Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/SerplulimabAnlotinib+SOC therapy |
| DLL3 TEAM | Experimental | Biological: DLL3 CAR-NK cells, Drug: Etoposide + Cisplatin/Carboplatin, Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/SerplulimabDLL3 CAR-NK cell+SOC therapy |
| XPO1 TEAM | Experimental | Drug: Selinexor, Drug: Etoposide + Cisplatin/Carboplatin, Drug: Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/SerplulimabSelinexor+SOC therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelinexorSelinexor 60 mg biw q21d | Drug | XPO1 TEAM |
| AnlotinibAnlotinib 12mg d1-14 qd PO | Drug | Anlotinib TEAM |
| DLL3 CAR-NK cells1.0×10^9 DLL3-CAR-NK+ cells d5 q6w | Biological | DLL3 TEAM |
| Etoposide + Cisplatin/CarboplatinEtoposide 100mg/m^2 d1-3+ cisplatin 75mg/m^2 d1-3 or Carboplatin AUC5 | Drug | Anlotinib TEAM, DLL3 TEAM, XPO1 TEAM |
| Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/SerplulimabUse immunotherapy according to the standard immunotherapy-combined-chemotherapy protocol. | Drug | Anlotinib TEAM, DLL3 TEAM, XPO1 TEAM |
Primary outcome
PFS
Time frame: through study completion, an average of 1 year
ORR
Time frame: through study completion, an average of 1 year
OS
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2025.
- Background: PubMed 38181741Liu 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.
- Background: PubMed 33493586Wang 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.
- Background: PubMed 39887933Qin 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Selinexor, Anlotinib and DLL3 CAR-NK cells in people with Extensive Stage Lung Small Cell Cancer, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dingzhi Huang, M.D (+86-22-23340123-3210, dingzhih72@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: through study completion, an average of 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07172412, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2025.