This is a Two-cohort, Exploratory Clinical Study Assessing the Activity of Benmelstobart Combined With Chemotherapy With or Without Anlotinib in Resectable Limited-Stage Small Cell Lung Cancer

NCT ID: NCT06978153

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-20
• Study Completion Date: 2027-11-01

Brief Summary

A total of 66 patients were enrolled in this exploratory study and randomly assigned to cohort 1 and cohort 2, with 33 patients in each group. Cohort 1: Neoadjuvant therapy (benmelstobart combined with chemotherapy and anlotinib, 3 cycles, every 21 days is a cycle). Surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. Adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. Patients who achieved R0 resection received adjuvant therapy (benmelstobart combined with anlotinib, 12 cycles, every 21 days is a cycle). Cohort 2: Neoadjuvant therapy (benmelstobart combined with chemotherapy, 3 cycles, every 21 days is a cycle). Surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. Adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. Patients who achieved R0 resection received adjuvant therapy (benmelstobart, every 21 days is a cycle) .

Conditions

Limited Stage Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Neoadjuvant therapy (benmelstobart combined with chemotherapy and anlotinib)

Cohort 1: Neoadjuvant therapy (benmelstobart combined with chemotherapy and anlotinib, 3 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day 1. Anlotinib, 10 mg, po, qd, was taken orally for 2 consecutive weeks and stopped for 1 week. Anlotinib was stopped 1 week before surgery. Etoposide, 100mg/m2, day 1\~3. Cisplatin, 75mg/m2，day 1; or Carboplatin, AUC 5, day 1. Surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. Adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. Patients who achieved R0 resection received adjuvant therapy (benmelstobart combined with anlotinib, 12 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1; anlotinib, 10 mg, po, qd, was taken orally for 2 weeks and stopped for 1 week.

Group Type: EXPERIMENTAL

benmelstobart combined with chemotherapy and anlotinib

Intervention Type: DRUG

Cohort 1: Neoadjuvant therapy (benmelstobart combined with chemotherapy and anlotinib, 3 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day 1. Anlotinib, 10 mg, po, qd, was taken orally for 2 consecutive weeks and stopped for 1 week. Anlotinib was stopped 1 week before surgery. Etoposide, 100mg/m2, day 1\~3. Cisplatin, 75mg/m2，day 1; or Carboplatin, AUC 5, day 1. Surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. Adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. Patients who achieved R0 resection received adjuvant therapy (benmelstobart combined with anlotinib, 12 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1; anlotinib, 10 mg, po, qd, was taken orally for 2 weeks and stopped for 1 week.

Cohort 2: Neoadjuvant therapy (benmelstobart combined with chemotherapy)

Cohort 2: Neoadjuvant therapy (benmelstobart combined with chemotherapy, 3 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1; Etoposide, 100mg/m2, day 1\~3; Cisplatin, 75mg/m2，day 1; or Carboplatin, AUC 5, day 1. Surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. Adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. Patients who achieved R0 resection received adjuvant therapy (benmelstobart, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1.

Group Type: EXPERIMENTAL

benmelstobart combined with chemotherapy

Intervention Type: DRUG

Cohort 2: Neoadjuvant therapy (benmelstobart combined with chemotherapy, 3 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1; Etoposide, 100mg/m2, day 1\~3; Cisplatin, 75mg/m2，day 1; or Carboplatin, AUC 5, day 1. Surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. Adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. Patients who achieved R0 resection received adjuvant therapy (benmelstobart, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1.

Interventions

benmelstobart combined with chemotherapy and anlotinib

Cohort 1: Neoadjuvant therapy (benmelstobart combined with chemotherapy and anlotinib, 3 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day 1. Anlotinib, 10 mg, po, qd, was taken orally for 2 consecutive weeks and stopped for 1 week. Anlotinib was stopped 1 week before surgery. Etoposide, 100mg/m2, day 1\~3. Cisplatin, 75mg/m2，day 1; or Carboplatin, AUC 5, day 1. Surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. Adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. Patients who achieved R0 resection received adjuvant therapy (benmelstobart combined with anlotinib, 12 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1; anlotinib, 10 mg, po, qd, was taken orally for 2 weeks and stopped for 1 week.

Intervention Type: DRUG

benmelstobart combined with chemotherapy

Cohort 2: Neoadjuvant therapy (benmelstobart combined with chemotherapy, 3 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1; Etoposide, 100mg/m2, day 1\~3; Cisplatin, 75mg/m2，day 1; or Carboplatin, AUC 5, day 1. Surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. Adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. Patients who achieved R0 resection received adjuvant therapy (benmelstobart, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients voluntarily participate in this study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up.
• Aged 18 to 75 years (inclusive) at the time of signing informed consent, regardless of gender.
• Histologically confirmed small cell lung cancer (SCLC).
• Confirmed as stage I-IIIB SCLC (T1-3N0-2M0) per AJCC 9th Edition.
• Patients who have received 1 cycle of chemotherapy are eligible; no other prior treatments are permitted.
• ECOG Performance Status (PS) 0 or 1.
• Assessed by the investigator as having no surgical contraindications.
• At least one measurable lesion per RECIST 1.1 criteria.
• Expected survival ≥8 weeks.
• Women of childbearing potential (aged 15-49) must have a negative serum pregnancy test within 7 days before treatment initiation and agree to use reliable contraception during the study until 8 weeks after discontinuation. Normal function of major organs meeting the following criteria:
• Hematologic tests (no blood transfusion, blood products, G-CSF, or hematopoietic stimulants within 14 days): Hemoglobin (Hb) ≥90 g/L; Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelets (PLT) ≥80×10⁹/L.
• Biochemical tests meeting: Total bilirubin (TBIL) ≤1.5×ULN; ALT/AST ≤2.5×ULN; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCr) ≥60 mL/min.
• Urine protein <2+; for patients not on anticoagulation: INR ≤1.5, APTT ≤1.5×ULN. Patients on full-dose or parenteral anticoagulants may enroll if dosing has been stable for ≥2 weeks and coagulation tests are within therapeutic ranges.

Exclusion Criteria

• Histologically confirmed mixed-type SCLC.
• Extensive-stage SCLC.
• ECOG PS >1.
• Active or untreated CNS metastases confirmed by CT/MRI during screening/prior imaging.
• Uncontrolled tumor-related pain.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage (≥1×/month).
• Uncontrolled/symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected serum calcium >ULN).
• Systemic immunostimulants (e.g., IFN-α, IL-2, TNF) within 4 weeks prior to enrollment (cancer vaccines allowed if prior).
• Systemic corticosteroids (>10 mg prednisone/day or equivalent) or immunosuppressants within 14 days, except: Replacement therapy (≤10 mg prednisone/day); Topical/ocular/intra-articular/nasal/inhaled steroids with minimal systemic absorption; Short-term (≤7 days) prophylactic use (e.g., contrast allergy) or for non-autoimmune conditions.
• Imaging-confirmed tumor invasion of major vessels or high risk of fatal hemorrhage per investigator; or cavitary/necrotic lung tumors.
• Other malignancies within 5 years except: cervical CIS, cured basal cell carcinoma, Ta/Tis bladder tumors.
• Prior use of anlotinib or other antiangiogenic agents.
• Prior anti-PD-1/PD-L1/CTLA-4 antibodies or other T-cell co-stimulation/checkpoint pathway therapies (e.g., ICOS, CD40/CD137/GITR/OX40 agonists).
• Hypersensitivity to anlotinib or benmelstobart components.
• Factors impairing oral drug intake (e.g., dysphagia, chronic diarrhea, intestinal obstruction).
• Uncontrolled comorbidities including:

1. Poorly controlled hypertension (SBP ≥150 mmHg, DBP ≥100 mmHg);

2. Grade ≥1 myocardial ischemia/infarction, arrhythmias (QTc ≥480 ms), or ≥NYHA Class II heart failure;

3. Abnormal coagulation (INR >1.5, PT >ULN+4s, APTT >1.5×ULN), bleeding tendency, or thrombolytic/anticoagulant therapy (prophylactic low-dose heparin [6,000-12,000 U/day] or aspirin [≤100 mg/day] allowed if INR ≤1.5);

4. Active/severe uncontrolled infections;

5. Cirrhosis, decompensated liver disease, active/chronic hepatitis requiring antivirals;

6. Renal failure requiring dialysis;

7. Immunodeficiency (HIV+, congenital/acquired immunodeficiency) or organ transplant history;

8. Poorly controlled diabetes (FBG >10 mmol/L);

9. Urine protein ≥++ or 24-h urine protein >1.0 g;

10. Epilepsy requiring treatment;

11. Non-healing wounds/fractures.

• Significant hemoptysis (>50 mL/day within 2 weeks) or clinically significant bleeding (e.g., GI bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ≥++).
• Interstitial lung disease (ILD), drug-induced ILD, steroid-requiring radiation pneumonitis, or active ILD.
• Arterial/venous thromboembolism within 6 months (e.g., stroke [including TIA], DVT, PE).
• Grade ≥2 peripheral neuropathy (excluding trauma-related).
• Major surgery/severe trauma with residual effects within 14 days.
• Concurrent clinical trials or <4 weeks from prior trial treatment.
• Live/attenuated vaccination within 30 days before benmelstobart or planned during study.
• History of severe hypersensitivity to monoclonal antibodies.
• Pregnant/lactating women.
• Uncontrolled psychiatric/neurological disorders affecting compliance.
• Other factors per investigator judgment that may lead to study termination (e.g., severe illness, lab abnormalities, or social/family constraints compromising safety/data collection).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tang-Du Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Yan Xiaolong Yan

Role: CONTACT

yanxiaolong@fmmu.edu.cn

+8615991269383

Other Identifiers

Shaanxi-Lung-03

Identifier Type: -

Identifier Source: org_study_id