Clinical trial NCT06978153: 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
Official title: Perioperative Treatment With Benmelstobart Combined With Chemotherapy With or Without Anlotinib in Resectable Limited-Stage Small Cell Lung Cancer: A Randomized, Two-Cohort, Multicenter, Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Limited Stage Small Cell Lung Cancer
Lead sponsor: Tang-Du Hospital
Sponsor class: OTHER
First posted: 2025-05-18
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Model Description
Primary purpose: TREATMENT

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) .


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).

Primary outcomes:
measure: event-free survival (EFS)
timeFrame: up to 2 years
Secondary outcomes:
measure: Major pathologic response rate (MPR)
timeFrame: 7 days after surgery
measure: Complete pathological response (pCR)
timeFrame: 7 days after surgery
measure: Objective response rate (ORR)
timeFrame: 7 days after surgery
measure: overall survival (OS)
timeFrame: up to 3 year
measure: Treatment-related adverse events evaluated according to CTCAE v5.0
timeFrame: up to 2 years
measure: Surgical complications evaluated according to the Clavien-Dindo classification
timeFrame: up to 2 years
Other outcomes:
Locations:
Study officials:
References: