Starting soon
Phase 2
Neoadjuvant Presurgical Becotatug Vedotin (MRG003) Plus Pucotenlimab (HX008) in Oral Cavity Squamous Cell Carcinoma
Condition(s) studied
Oral Squamous Cell CarcinomaHead and Neck CancerLocally Advanced Head and Neck CancerNeoadjuvant Therapy
Investigational drug(s) / intervention(s)
Becotatug Vedotin (MRG003)Pucotenlimab
Becotatug Vedotin (MRG003): Anti-EGFR antibody-drug conjugate (ADC) composed of a recombinant humanized anti-EGFR monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable valine-citrulline linker. Administered at 2.3 mg/kg intravenously every 3 weeks for 3 cycles.
Pucotenlimab: Humanized anti-PD-1 monoclonal antibody (IgG4) that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2. Administered at 200 mg intravenously every 3 weeks for 3 cycles.
Study summary
This is a phase 2, open-label, single-arm clinical trial evaluating neoadjuvant therapy with Becotatug vedotin (MRG003) combined with Pucotenlimab (HX008) in patients with previously untreated, resectable stage III-IVA oral cavity squamous cell carcinoma (OSCC) with a PD-L1 Combined Positive Score (CPS) of 1 or higher.
Eligible participants will receive 3 cycles of neoadjuvant treatment (Becotatug vedotin 2.3 mg/kg plus Pucotenlimab 200 mg, intravenously, every 3 weeks), followed by radical surgery 2-3 weeks after the last cycle of neoadjuvant therapy. Postoperative adjuvant radiotherapy will be stratified based on pathological response and risk factors: patients achieving major pathological response (MPR, defined as ≤10% residual viable tumor) with negative margins and no extranodal extension (ENE) will receive de-escalated radiotherapy (50-54 Gy); patients not achieving MPR or with high-risk features will receive standard radiotherapy (60-66 Gy) with or without concurrent cisplatin chemotherapy.
The primary endpoint is major pathological response (MPR). Secondary endpoints include objective response rate (ORR), pathological complete response (pCR), event-free survival (EFS), overall survival (OS), and safety profile. Exploratory biomarkers will be assessed in tumor tissue and peripheral blood.
A total of 32-33 participants will be enrolled using a Simon two-stage optimal design (α=0.05, power=80%).
Eligibility
Inclusion Criteria:
* Voluntary participation with written informed consent, good compliance, and willingness to complete follow-up.
* Age ≥18 years and ≤70 years, regardless of gender.
* ECOG performance status score of 0 or 1.
* Histopathologically confirmed, previously untreated, primary oral cavity squamous cell carcinoma (OSCC); central laboratory-confirmed PD-L1 Combined Positive Score (CPS) ≥1; clinical stage III-IVA (AJCC 8th edition) with potential for curative surgical resection as assessed by the investigator; no evidence of definite locoregional residual or distant metastasis.
* Adequate organ function within 14 days prior to the first dose, without transfusion or hematopoietic growth factor support:
* Bone marrow: ANC ≥1.5×10\^9/L; platelet count ≥100×10\^9/L; hemoglobin ≥90 g/L.
* Liver: TBIL ≤1.5×ULN; AST/ALT ≤3.0×ULN; ALP ≤2.5×ULN; serum albumin ≥28 g/L.
* Kidney: creatinine clearance (Ccr) ≥40 mL/min (calculated by Cockcroft-Gault formula) or serum creatinine ≤1.5×ULN.
* Coagulation: INR ≤1.5×ULN and APTT ≤1.5×ULN (excluding patients receiving therapeutic anticoagulation).
* Cardiac: LVEF ≥50% with no significant cardiac dysfunction.
* Negative serum pregnancy test within 7 days prior to the first dose for women of childbearing potential; all fertile male and female participants must agree to use highly effective contraception from signing of informed consent through 1 year after the last dose of Pucotenlimab.
Exclusion Criteria:
* Age \>70 years or \<18 years.
* History of other malignancies within the past 5 years, except adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
* HIV infection.
* HBsAg positive with HBV DNA \>200 IU/mL or 1000 copies/mL.
* HCV antibody positive.
* Severe concurrent diseases that may pose significant risks or affect trial compliance, including unstable cardiac disease, renal disease, chronic hepatitis, poorly controlled diabetes (fasting blood glucose \>1.5×ULN), severe cognitive impairment, or psychiatric disorders.
* Active pulmonary tuberculosis infection within the past 1 year, or history of active tuberculosis \>1 year ago unless documented prior standard anti-tuberculosis treatment.
* History of interstitial lung disease.
* Active, known, or suspected autoimmune disease. Exceptions: type I diabetes, hypothyroidism requiring only hormone replacement therapy, and skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia).
* Systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive therapy within 28 days prior to signing informed consent. Patients receiving ≤10 mg/day prednisone equivalent or inhaled/topical corticosteroids are eligible.
* Live vaccination within 30 days prior to signing informed consent or planned during the study.
* Prior surgery, chemotherapy, radiotherapy, immunotherapy, or other anti-tumor therapy for head and neck cancer (excluding diagnostic procedures).
* Known hypersensitivity to macromolecular protein preparations, or any component of Becotatug vedotin, Pucotenlimab, or cisplatin.
* Pregnancy, lactation, or anticipated pregnancy during the study period.
Primary outcome measure(s)
- Major Pathological Response (MPR) Rate — At the time of surgery, following 3 cycles of neoadjuvant therapy (each cycle is 21 days)
MPR is defined as the proportion of participants with ≤10% residual viable tumor cells in the resected primary tumor specimen following neoadjuvant therapy, as assessed by central pathology review.
Trial sites (2)
| Facility | City | Region | Status |
|---|
| Hospital of Stomatology, Sun Yat-sen University |
Guangzhou |
Guangdong |
|
| Sun Yat-sen University Cancer Center |
Guangzhou |
Guangdong |
|