EGFR-ADC (Becotatug Vedotin) Combined With PD-1 Inhibitor (Pucotenlimab) in Neoadjuvant Treatment of Advanced Penile Cancer

NCT07518979 | Not Yet Recruiting Phase 2

• 1 other identifier: MH-Penile-002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study is a Phase II research trial focused on a new preoperative treatment for men with advanced penile squamous cell carcinoma (a type of penile cancer). The cancer may be hard to treat with penile-sparing surgery, or it may have spread to nearby lymph nodes (like groin lymph nodes). We are testing a combination of two medicines: Becotatug vedotin (a targeted therapy that finds and kills cancer cells with high levels of a protein called EGFR) and Pucotenlimab (an immunotherapy that helps your body's immune system fight cancer). The goal is to see if this combination can shrink the tumor, make surgery more likely to remove all cancer cells, and improve treatment outcomes-while keeping side effects manageable. Who can join? To be eligible, you must: Be a man 18 years or older with confirmed penile squamous cell carcinoma; Have cancer that is hard to treat with penile-sparing surgery or has spread to regional lymph nodes; Have cancer cells that test positive for EGFR (a protein most penile cancers make); Have not received prior systemic cancer treatment (or had recurrence more than 6 months after adjuvant therapy for radical resection); Have adequate organ function (e.g., healthy heart, liver, and kidney function) to tolerate treatment; Understand the study and voluntarily agree to participate by signing an informed consent form. What will happen during the study? Screening (up to 28 days): You will have tests to confirm eligibility, including imaging scans, blood work, and EGFR testing on your tumor sample. Preoperative treatment (4-6 cycles): You will receive intravenous infusions of Becotatug vedotin (2.0 mg/kg) and Pucotenlimab (200 mg) every 3 weeks. Every 6 weeks, you will have imaging scans to check if the tumor is shrinking. Surgery: If the tumor responds to treatment (assessed by a team of doctors), you will undergo radical surgery to remove the cancer. If surgery is successful, you may continue Pucotenlimab as adjuvant therapy for 1 year. Follow-up: After treatment, you will be checked every 3 months for 2 years to monitor for cancer recurrence and long-term side effects. What are the study goals? Primary goal: To find out how many patients can have successful surgery to remove all visible cancer (R0 resection) after the combination treatment. Secondary goals: To measure how much the tumor shrinks (objective response rate), if the cancer stage improves (downstaging rate), if surgery removes all cancer cells (pathological complete response rate), how long patients stay cancer-free (disease-free survival), and how safe the treatment is. What are the potential risks? As with any cancer treatment, this combination may cause side effects. Common expected side effects include skin reactions (e.g., rash), digestive issues, changes in blood cell counts, liver function changes, and immune-related reactions (e.g., thyroid problems, lung inflammation). These side effects will be closely monitored by the study team, and treatments to manage them will be provided. This study is being conducted at West China Hospital, Sichuan University. It is a single-arm trial (all participants receive the same combination treatment) and will enroll about 60 patients. The study is expected to run from April 2026 to April 2028.

Conditions

Penile Cancer

Keywords

penile cancer; ADC; PD-1

Outcome Measures

Primary Outcomes (1)

• Surgical Resection Rate

  Proportion of patients who achieve R0 resection (no residual tumor cells at margins) after neoadjuvant therapy, confirmed by surgical records and postoperative pathological reports.

  Up to 6 months after the start of neoadjuvant therapy (after completion of 4-6 cycles of treatment and MDT evaluation).

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  Every 6 weeks during neoadjuvant therapy, up to 6 months.

• Downstaging Rate

  After completion of neoadjuvant therapy (up to 6 months).

• Pathological Complete Response (pCR) Rate

  Within 1 month after surgery.

• Major Pathological Response (MPR) Rate

  Within 1 month after surgery.

• Tumor Regression Grade (TRG)

  Within 1 month after surgery.

Study Arms (1)

Becotatug Vedotin + Pucotenlimab Neoadjuvant Arm

EXPERIMENTAL

This single-arm, phase II intervention arm evaluates neoadjuvant therapy with Becotatug Vedotin (an EGFR-targeting antibody-drug conjugate) combined with Pucotenlimab (a PD-1 inhibitor) in patients with EGFR-expressing locally advanced penile squamous cell carcinoma (PSCC) who have penile preservation difficulty or regional lymph node metastasis. All eligible participants receive the same standardized regimen: intravenous infusion of Becotatug Vedotin at 2.0 mg/kg and Pucotenlimab at 200 mg, administered once every 3 weeks for 4 to 6 cycles. Following neoadjuvant treatment, tumor resectability is assessed by a multidisciplinary team (MDT). Patients with resectable disease undergo radical surgery (penile-sparing resection or total/partial penectomy plus inguinal/pelvic lymph node dissection as indicated). Those achieving R0 resection (complete resection with negative margins) receive adjuvant Pucotenlimab for 1 year to consolidate antitumor immunity.

Drug: Becotatug Vedotin; Drug: Pucotenlimab

Interventions

Becotatug Vedotin DRUG

Becotatug vedotin is an EGFR-targeted antibody-drug conjugate (ADC) composed of a high-affinity anti-EGFR monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable valine-citrulline linker. In this phase II neoadjuvant trial, it is administered intravenously at a dose of 2.0 mg/kg once every 3 weeks for 4-6 cycles, in combination with Pucotenlimab, for patients with EGFR-expressing locally advanced penile squamous cell carcinoma.

Also known as: MRG003

Becotatug Vedotin + Pucotenlimab Neoadjuvant Arm

Pucotenlimab DRUG

Pucotenlimab is a humanized, high-affinity anti-PD-1 monoclonal antibody that blocks PD-1/PD-L1/PD-L2 binding to reactivate antitumor immunity. In this trial, it is administered intravenously at 200 mg once every 3 weeks: 4-6 cycles as neoadjuvant therapy with Becotatug vedotin, followed by 1 year of adjuvant therapy for patients achieving R0 resection, for EGFR-expressing locally advanced penile squamous cell carcinoma.

Becotatug Vedotin + Pucotenlimab Neoadjuvant Arm

Eligibility Criteria

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

You may qualify if:

• Left ventricular ejection fraction (LVEF) ≥50%;
• Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥3.0×10⁹/L, absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet (PLT) ≥80×10⁹/L;
• Total bilirubin (TBIL) ≤1.5×ULN, AST/ALT ≤2.5×ULN (≤5×ULN for liver metastasis), serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL/min; （8）Voluntarily participate, understand the study, and sign informed consent form.

Sponsors & Collaborators

• Jiyan Liu: lead
• West China Hospital: collaborator
• Lepu Medical Technology (Beijing) Co., Ltd.: collaborator

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Penile Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Penile Diseases; Male Urogenital Diseases

Central Study Contacts

Hong-Shuai Li, Dr

CONTACT

+86-18384262516; lihongshuai456@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: SPONSOR INVESTIGATOR
• PI Title: Neoadjuvant Therapy with EGFR-ADC (Becotatug vedotin) Combined with PD-1 Inhibitor (Pucotenlimab) for Penile Squamous Cell Carcinoma with Penile Preservation Difficulty or Regional Lymph Node Metastasis: A Single-Arm, Phase II Clinical Trial

Model Details: This is a single-arm, open-label, phase II interventional study. All enrolled participants will receive the same neoadjuvant treatment regimen: Becotatug vedotin (EGFR-ADC, 2.0 mg/kg) combined with Pucotenlimab (anti-PD-1 inhibitor, 200 mg) administered intravenously every 3 weeks for 4-6 cycles. No control group or randomization is applied. Following treatment response evaluation by a multidisciplinary team, eligible patients will undergo radical surgery, and those achieving R0 resection may receive 1 year of adjuvant Pucotenlimab.

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 9, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2031
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)