Becotatug Vedotin Combined With a PD-1 Inhibitor in the Treatment of Locally Advanced Recurrent Nasopharyngeal Carcinoma.

An Exploratory, Single-arm, Phase II Study of Becotatug Vedotin Combined With a PD-1 Inhibitor in the Treatment of Locally Advanced Recurrent Nasopharyngeal Carcinoma.

This study plans to enroll patients with histologically or cytologically confirmed locally recurrent nasopharyngeal carcinoma. After signing informed consent, eligible subjects will receive three cycles of standard-dose becotatug vedotin combined with a PD-1 inhibitor. Following treatment, imaging assessment and surgical evaluation will be performed. Subjects deemed operable will undergo endoscopic nasal surgery, after which the MDT (multidisciplinary team) will discuss and determine a maintenance treatment plan. For subjects who are not eligible for surgery, the MDT will decide on either maintenance therapy or a switch to an alternative treatment regimen.

Inclusion Criteria:

• Written informed consent obtained prior to any trial-related procedures.
• ≥ 18 years of age.
• Histologically or cytologically confirmed recurrent nasopharyngeal carcinoma (locoregional recurrence and/or regional lymph node recurrence), without distant metastases. Including patients with local recurrence at T2 stage and/or retropharyngeal lymph node metastasis adjacent to the internal carotid artery.
• At least one lesion at baseline meeting RECIST 1.1 criteria for target lesions (TL). Tumor assessment must be performed by CT or MRI scan within 28 days before treatment.
• ECOG performance status 0-1.
• Life expectancy ≥ 3 months.
• Adequate organ function for drugs and surgery
• For female patients of childbearing potential, a urine or serum pregnancy test must be performed within 3 days prior to the first dose of study drug (Cycle 1 Day 1) and the result must be negative. If the urine pregnancy test cannot be confirmed as negative, a blood pregnancy test is required. Non-childbearing potential is defined as postmenopausal for at least 1 year, or having undergone surgical sterilization or hysterectomy.
• If there is a risk of conception, all subjects (male or female) must use contraceptive methods with a failure rate of < 1% per year during the entire treatment period and for 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy, if applicable).

Exclusion Criteria:

• Diagnosis of any malignancy other than nasopharyngeal carcinoma within 5 years prior to first dose (excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ that has been radically resected).
• Prior treatment with an ADC drug containing MMAE as the payload.
• Known active bleeding signs of the lesion under endoscopy.
• Currently participating in an interventional clinical study, or having received another investigational drug or used an investigational device within 4 weeks prior to first dose.
• Systemic treatment with traditional Chinese patent medicine with anti-tumor indications or immunomodulatory agents (including thymosin, interferon, interleukin; excluding topical use for pleural effusion control) within 2 weeks prior to first dose.
• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, glucocorticoids, or immunosuppressants) within 2 years prior to first dose. Replacement therapies (e.g., thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic treatment.
• Receiving systemic glucocorticoid therapy (excluding intranasal, inhaled, or other routes of topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to first dose.

Note: Physiological doses of glucocorticoids (≤ 10 mg/day prednisone or equivalent) are permitted.

• History of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Failure to fully recover from toxicity and/or complications caused by any prior intervention (i.e., ≤ Grade 1 or returned to baseline, excluding fatigue or alopecia) before starting treatment.
• Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive).
• Untreated active hepatitis B (defined as HBsAg positive with detectable HBV-DNA copy number exceeding the upper limit of normal of the central laboratory).

Note: Hepatitis B subjects meeting the following criteria may also be enrolled:

HBV viral load < 1000 copies/mL (200 IU/mL) prior to first dose; subjects should receive anti-HBV therapy throughout the study chemotherapy period to prevent viral reactivation.

For subjects who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring for viral reactivation is needed.

Subjects with active HCV infection (HCV antibody positive and HCV-RNA level above the lower limit of detection).

• Receipt of live vaccine within 30 days prior to first dose (Cycle 1, Day 1). Note: Injectable inactivated influenza vaccines for seasonal flu are allowed within 30 days prior to first dose; however, intranasally administered live attenuated influenza vaccines are not permitted.
• Pregnant or lactating women. Presence of any severe or uncontrolled systemic disease.