Benmelstobart-Anlotinib-Chemo for Neoadjuvant Oral Cancer

NCT06848439 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: BENMEL-ANLO-CHEMO-II
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Exploring the Safety and Efficacy of Benmelstobart Combined with Anlotinib and Chemotherapy as Neoadjuvant Therapy Followed by Surgery and Postoperative Radiotherapy in Patients with Locally Advanced Oral Cancer This is a single-center, Phase II study targeting patients with stage III-IVb locally advanced oral squamous cell carcinoma who meet the inclusion and exclusion criteria. The neoadjuvant therapy consists of Benmelstobart combined with Anlotinib and chemotherapy for 3 cycles (21 days per cycle). Surgery is performed within 2 weeks after completing neoadjuvant therapy. Postoperative adjuvant treatment is selected based on pathological grading: Group A (Pathological Complete Response, pCR): Postoperative radiotherapy (RT) alone: 40Gy/5 weeks. Group B (Major Pathological Response, MPR): Postoperative radiotherapy (RT) alone: 50Gy/5 weeks. Group C (Partial Pathological Response/No Pathological Response): Low-to-intermediate risk patients (no extracapsular nodal extension and negative margins): RT: 60Gy/6 weeks. High-risk patients (extracapsular nodal extension and/or positive margins): Concurrent chemoradiotherapy (CCRT): 60-66Gy/6-6.6 weeks + Cisplatin: 60mg/m² every 3 weeks, 2-3 cycles. Additionally, all patients will receive adjuvant Benmelstobart 3-4 weeks after surgery, followed by Benmelstobart maintenance therapy (total treatment duration of 1 year).

Conditions

Mouth Neoplasms; Neoadjuvant Therapy; Immunotherapy; Molecular Targeted Therapy

Keywords

Mouth Neoplasms; Neoadjuvant therapy; Immunotherapy; Molecular Targeted Therapy

Outcome Measures

Primary Outcomes (1)

• Disease-free survival at 2 years, DFS

  Two years after enrollment

Secondary Outcomes (6)

• ORR

  Ten weeks after enrollment (after completion of neoadjuvant therapy)

• Major pathological response, MPR

  Twelve weeks after enrollment (after neoadjuvant therapy and surgery)

• pCR

  Twelve weeks after enrollment (after neoadjuvant therapy and surgery)

• LRFS at 2 years

  Two years after enrollment

• DMFS at 2 years

  Two years after enrollment

Study Arms (1)

Benmelstobart-Anlotinib-Chemo

EXPERIMENTAL

Drug: benmelstobart-Anlotinib-Chemo

Interventions

benmelstobart-Anlotinib-Chemo DRUG

Neoadjuvant Treatment Regimen : Benmelstobart: 1200mg, Day 1, IV (21 days per cycle); Anlotinib: 10mg, Days 1-14, orally (21 days per cycle); Cisplatin: 60mg/m², Day 1, IV (21 days per cycle); Albumin-bound Paclitaxel: 260mg/m², IV infusion, Day 1 (21 days per cycle). Total of 3 cycles. Surgery is performed within 2 weeks after completing neoadjuvant therapy. Postoperative adjuvant treatment is selected based on pathological grading: Group A (pCR): Postoperative RT alone: 40Gy/5 weeks. Group B (MPR): Postoperative RT alone: 50Gy/5 weeks. Group C (partial pathological response/no pathological response) : low and intermediate-risk patients: RT: 60Gy/6w; High-risk patients: CCRT: 60-66Gy/6-6.6w + cisplatin: 60mg/m2 Q3W, 2-3 cycles. All patients also received adjuvant Benmelstobart 3-4 weeks after surgery, as well as maintenance Benmelstobart for a total duration of 1 year.

Benmelstobart-Anlotinib-Chemo

Eligibility Criteria

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

You may qualify if:

• Age 18-75 years;
• ECOG PS score of 0-1;
• Pathologically confirmed untreated oral squamous cell carcinoma patients, classified as stage III-IVb according to the AJCC (8th edition) staging system;
• Women of childbearing potential must have taken reliable contraceptive measures or have a negative pregnancy test (serum or urine) within 7 days prior to enrollment, and be willing to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of the study drug, or be surgically sterilized. For men, they must agree to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of the study drug, or be surgically sterilized;
• Signed informed consent form by the participant, with good compliance.

You may not qualify if:

• Potential subjects must be excluded from the study if they meet any of the following criteria:
• Prior treatment with PD-1/PD-L1/CTLA-4 antibodies.
• Tumor invasion of major blood vessels.
• Requirement for systemic corticosteroid therapy (\>10 mg prednisone equivalent per day) or other immunosuppressive treatment within 14 days before administration or during treatment. Inhaled or topical steroids and adrenal corticosteroid replacement therapy at ≤10 mg/day prednisone equivalent are allowed in the absence of active autoimmune disease.
• History of any active immune-related or autoimmune disease, or a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active or uncontrolled severe infection (≥ Grade 2 NCI CTCAE v5.0 infection) within 4 weeks prior to enrollment.
• Coagulation disorders (INR \>1.5, prothrombin time (PT) \> ULN + 4 sec, or APTT \>1.5 × ULN), a tendency for bleeding, or undergoing thrombolytic or anticoagulant therapy. Note: The use of low-dose heparin (adult daily dose of 6,000-12,000 U) or low-dose aspirin (daily dose ≤100 mg) for prophylactic purposes is allowed if INR ≤1.5.
• Imaging evidence of tumor invasion of major blood vessels or tumors highly likely to invade major blood vessels and cause fatal hemorrhage during the study, as assessed by the investigator.
• Any signs or history of a bleeding tendency, regardless of severity. Patients with bleeding or hemorrhagic events (≥CTCAE Grade 2) within 4 weeks prior to randomization, or those with unhealed wounds, ulcers, or fractures.
• Major organ dysfunction:
• Hematological abnormalities (without correction via blood transfusion, blood products, G-CSF, or other hematopoietic stimulants within 14 days):
• Hemoglobin (HB) \<90 g/L.
• Absolute neutrophil count (ANC) \<1.5 × 10⁹/L.
• Platelets (PLT) \<100 × 10⁹/L.
• Biochemical abnormalities:

Sponsors & Collaborators

• Jiangsu Cancer Institute & Hospital: lead
• Affiliated Stomatological Hospital of Nanjing Medical University: collaborator

Study Sites (1)

Affiliated Stomatological Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Location

MeSH Terms

Conditions

Mouth Neoplasms

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases

Central Study Contacts

Lirong Wu, Doctor of Medicine

CONTACT

86+13701588737; wulirong126@126.com

Xiaomeng Song, Doctor of Medicine

CONTACT

sxm2081@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician; Associate Professor

Study Record Dates

• First Submitted: February 16, 2025
• First Posted: February 27, 2025
• Study Start: June 15, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)