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

Overview

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) .

Interventions

• Drug 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. Adjuv
• 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, eve

Primary outcome measures

• event-free survival (EFS) [Time frame: up to 2 years]

Secondary outcome measures (6)

• Major pathologic response rate (MPR) [Time frame: 7 days after surgery]
• Complete pathological response (pCR) [Time frame: 7 days after surgery]
• Objective response rate (ORR) [Time frame: 7 days after surgery]
• overall survival (OS) [Time frame: up to 3 year]
• Treatment-related adverse events evaluated according to CTCAE v5.0 [Time frame: up to 2 years]
• Surgical complications evaluated according to the Clavien-Dindo classification [Time frame: up to 2 years]

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:

• Poorly controlled hypertension (SBP ≥150 mmHg, DBP ≥100 mmHg);
• Grade ≥1 myocardial ischemia/infarction, arrhythmias (QTc ≥480 ms), or ≥NYHA Class II heart failure;
• 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);
• Active/severe uncontrolled infections;
• Cirrhosis, decompensated liver disease, active/chronic hepatitis requiring antivirals;
• Renal failure requiring dialysis;
• Immunodeficiency (HIV+, congenital/acquired immunodeficiency) or organ transplant history;
• Poorly controlled diabetes (FBG >10 mmol/L);
• Urine protein ≥++ or 24-h urine protein >1.0 g;
• Epilepsy requiring treatment;
• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06978153 · Shaanxi-Lung-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗