Pucotenlimab Combined With Becotatug Vedotin in Advanced Cutaneous Squamous Cell Carcinoma

Official title

Pucotenlimab Combined With Becotatug Vedotin in Advanced Cutaneous Squamous Cell Carcinoma: A Single-Arm, Multicenter, Prospective Phase II Clinical Trial

Overview

Study Design The study plans to enroll 38 patients. A Simon's two-stage design is employed. Based on historical data, the objective response rate (ORR) for patients meeting the inclusion criteria and receiving PD-1 inhibitor monotherapy is approximately 30%. The expected ORR for the combination of Pucotenlimab and Vebreltus is 55%. With a one-sided α=0.05 and 80% power, 9 patients will be enrolled in the first stage. If ≥2 patients achieve a partial response (PR) or complete response (CR), the study will proceed to the second stage. An additional 25 patients will be enrolled in the second stage, resulting in a total of 34 patients. If ≥15 patients in the total population achieve a PR, the study endpoint is considered met. Accounting for a 10% dropout rate, a total of 38 patients will be enrolled. Study Procedures After providing full informed consent and passing screening, eligible subjects will receive treatment with Vebreltus 2.0 mg/kg and Pucotenlimab 200 mg. On the first day of each treatment cycle, patients will receive an intravenous infusion of Pucotenlimab (infusion duration: 60 min ± 15 min, with the first cycle infusion lasting no less than 60 minutes). At least 30 minutes after the completion of the Pucotenlimab infusion, the Vebreltus infusion will commence (infusion duration: 60 min ± 15 min, with the first cycle infusion lasting no less than 60 minutes). Patients will receive the combination therapy once every 3 weeks until completion of 2 years of treatment or until the occurrence of a protocol-defined treatment discontinuation event. Following the end of treatment, each subject will undergo a 30-day (+7 days) safety follow-up to monitor adverse events and clinically relevant events. Post-treatment survival follow-up will be conducted every 12 weeks (±7 days). For subjects who discontinue treatment for reasons other than disease progression/death and do not initiate new anti-cancer therapy, tumor imaging assessments will continue per the original schedule until disease progression, initiation of new anti-cancer therapy, withdrawal of consent, loss to follow-up, or death, whichever occurs first. After enrollment, tumor response will be assessed according to RECIST v1.1 and iRECIST criteria. Imaging evaluations will be performed every 6 weeks (±7 days) from the first dose for the first 54 weeks, and then every 9 weeks (±7 days) thereafter (regardless of any delays in study drug administration), until iRECIST-confirmed progressive disease (iPD), initiation of new anti-cancer therapy, withdrawal of informed consent, loss to follow-up, or death, whichever occurs first. Exploratory Analysis This study will analyze the correlation between biomarkers in patient tumor tissue/blood samples (e.g., EGFR expression, PD-L1 CPS score, TILs) collected before and after treatment and clinical efficacy endpoints (e.g., ORR, PFS, DoR).

Interventions

• Drug Pucotenlimab
  The medications are administered via intravenous infusion. Pucotenlimab is given at a fixed dose of 200 mg, The infusion time is 60 ± 15 minutes (if infusion-related reactions occur, the infusion duration may be extended, up to a maximum of 4 hours). Dosing occurs on the first day of each 3-week cycle (Q3W). Pucotenlimab should be given first. For the first cycle, the infusion time for both drugs must not be less than 60 minutes.
• Drug Becotatug Vedotin
  The medications are administered via intravenous infusion. Becotatug Vedotin is dosed at 2.0 mg/kg based on the patient's actual body weight. The infusion time for Becotatug Vedotin is 60 ± 15 minutes (if infusion-related reactions occur, the infusion duration may be extended, up to a maximum of 4 hours). Dosing occurs on the first day of each 3-week cycle (Q3W). The infusion of Becotatug Vedotin should start at least 30 minutes after the completion of the Pucotenlimab infusion. For the first cy

Primary outcome measures

• Objective Response Rate [Time frame: up to 2 years]

Secondary outcome measures (4)

• Disease Control Rate [Time frame: up to 2 years]
• Progression-Free Survival [Time frame: up to 2 years]
• Duration of Response [Time frame: up to 2 years]
• Overall Survival [Time frame: up to 2 years]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form and agree to comply with the protocol requirements.
• Age ≥18 years and ≤80 years on the day of signing the informed consent form, regardless of gender.
• Life expectancy ≥12 weeks.
• Histopathologically confirmed cutaneous squamous cell carcinoma (cSCC), which is either locally advanced and inoperable (including recurrence after ≥2 prior surgeries, or deemed unresectable by a surgeon, or where surgery may lead to severe complications or deformity) or metastatic.
• Have received 0-1 prior lines of systemic chemotherapy for advanced cSCC, and have experienced disease progression during or after the most recent treatment (relapse within 6 months after completing adjuvant therapy is considered as one line of therapy).
• Able to provide tumor tissue specimens (paraffin blocks, paraffin-embedded sections, or fresh tissue sections) from a primary or metastatic site for pathological testing. The most recent archived tumor tissue specimen should be used. If archived tissue is unavailable, a new biopsy must be performed.
• Have at least one measurable lesion at baseline according to RECIST 1.1 criteria (the longest diameter ≥10 mm on CT scan, or short axis ≥15 mm for lymph nodes; measurable lesions should not have been irradiated, unless progression has been demonstrated within a prior radiation field or after local therapy). Digital photography may be used for superficial lesions.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to treatment initiation.
• No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to treatment initiation.
• Adequate organ function within 7 days prior to treatment initiation, defined as:

(1)Bone Marrow Function: Absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥90 g/L; and no transfusion or blood product administration within 14 days prior to the first dose, and no treatment with biologic response modifiers (e.g., G-CSF, erythropoietin) within 7 days prior to the first dose.

(2)Liver Function: For patients without liver metastases: total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN. For patients with liver metastases: TBIL ≤1.5 × ULN, ALT and AST ≤5 × ULN.

(3)Renal Function: Serum creatinine (Cr) ≤1.5 × ULN, or creatinine clearance (Ccr) ≥50 mL/min (calculated using the Cockcroft-Gault formula) (4)Coagulation Function: International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (APTT) ≤1.5 × ULN (unless the patient is receiving therapeutic anticoagulation).

11.Men and women of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 6 months after the last dose of the investigational product. Women of childbearing potential include premenopausal women and women within 2 years of menopause. A negative serum pregnancy test result is required for women of childbearing potential within ≤7 days before the first dose of the investigational product.

Exclusion criteria

• History of other malignancies within the past five years, except for cured cervical carcinoma in situ, thyroid cancer, or cutaneous basal cell carcinoma.
• Prior receipt of any of the following treatments:

• Any prior therapy targeting anti-PD-1, anti-PD-L1, PD-L2, CD137, CTLA-4 antibodies, or any other antibodies/drugs specifically targeting T-cell costimulation or immune checkpoint pathways;
• Any prior EGFR monoclonal antibody therapy;
• Investigational drug administration within 28 days before the first dose;
• Anticancer chemotherapy within 21 days before the first dose (washout period ≥14 days for oral fluoropyrimidines, leucovorin, or weekly paclitaxel chemotherapy; ≥42 days for nitrosoureas or mitomycin);
• Radiotherapy within 28 days before the first dose, or palliative radiotherapy for bone metastases within 2 weeks;
• Major surgery within 28 days before the first dose without full recovery, or planned major surgery within the first 12 weeks after receiving the study drug.
• Symptomatic brain or leptomeningeal metastases (unless treated >6 months prior, with negative imaging within 4 weeks before enrollment, and stable neurological status without steroid therapy).
• Any severe or uncontrolled systemic disease per investigator's judgment, including poorly controlled hypertension (systolic BP >160 mmHg or diastolic BP >100 mmHg), uncontrolled diabetes, or active bleeding signs.
• Poorly controlled cardiac diseases, including NYHA Class II or higher heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant supraventricular/ventricular arrhythmias requiring treatment.
• Active infections, including:

Hepatitis B (HBsAg-positive AND HBV DNA ≥2000 IU/mL, excluding drug-induced or other non-viral hepatitis);

Hepatitis C (anti-HCV antibody-positive AND HCV RNA above the lower limit of detection);

HIV infection; or uncontrolled active bacterial, viral, fungal, rickettsial, or parasitic infections (unless treated and resolved before study drug initiation).

• History of hypersensitivity to any component of Pucotenlimab or Vebreltus (e.g., histidine, histidine hydrochloride, sucrose, mannitol, polysorbate 80), or ≥Grade 3 allergic reactions to macromolecular protein preparations/monoclonal antibodies.
• Primary immunodeficiency history or active autoimmune disease requiring immunosuppressants or systemic glucocorticoids (dose ≥10 mg/day prednisone or equivalent within 2 weeks before enrollment).

Note: Patients with type I diabetes, stable hypothyroidism on hormone replacement, psoriasis/eczema not requiring systemic therapy, or vitiligo may be enrolled. Topical/inhaled corticosteroids or short-term (≤7 days) glucocorticoid use for non-autoimmune conditions are exempted.

• History or presence of interstitial lung disease, radiation pneumonitis, severe chronic obstructive pulmonary disease, severe respiratory insufficiency, or symptomatic bronchospasm.
• Positive serum pregnancy test, lactation, or unwillingness to use adequate contraception during the study and for 6 months after the last dose.
• Other conditions deemed inappropriate for participation by the investigator (e.g., alcohol/drug abuse).

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Fudan University Shanghai Cencer Center, Shanghai, Shanghai — Shanghai

Identifiers

NCT: NCT07394244 · Fudan CSCC-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗