Neoadjuvant Pucotenlimab and Becotatug Vedotin for Locally Advanced Penile Cancer

NCT07767266 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2026-FXY-152
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multicenter, single-arm Phase 2 clinical trial evaluating neoadjuvant pucotenlimab (anti-PD-1 immunotherapy) combined with becotatug vedotin (EGFR-targeted antibody-drug conjugate, ADC) for adults with locally advanced penile squamous cell carcinoma. Eligible patients have high-risk disease defined as T4 primary tumor with any nodal status or any T stage with N2-N3 lymph node metastasis and no distant metastasis. All participants receive up to 4 cycles of combination neoadjuvant therapy every 3 weeks. After treatment completion, a multidisciplinary team will assess if consolidative surgery can be performed. Patients who undergo surgery will continue single-agent pucotenlimab adjuvant treatment for 17 additional cycles (approximately 1 year). The primary goal is to measure the pathological complete response (pCR) rate. Secondary goals include objective response rate (ORR), progression-free survival (PFS),overall survival (OS) and safty profiles. Blood and tumor tissue samples will be collected to explore biomarkers that may predict treatment response and drug resistance. A total of 29 male patients will be enrolled.

Conditions

Penile Cancer; Penile Squamous Cell Carcinoma (PSCC)

Keywords

Penile cancer; Immunotherapy; Antibody-drug conjugate; Pucotenlimab; Becotatug Vedotin

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Remission (pCR) Rate

  Percentage of patients achieving pathological complete remission, defined as no residual invasive tumor cells in primary penile lesion and resected regional lymph nodes after neoadjuvant therapy and consolidative surgery.

  Within 4 weeks after consolidative surgery

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Evaluation at the end of Cycle 2 or 4 (each cycle is 21 days) of neoadjuvant treatment

• Progression-Free Survival (PFS)

  From the date of study enrollment until the date of first documented tumor progression or death from any cause (whichever occurs first), assessed up to 12 months

• Overall Survival (OS)

  From the date of study enrollment to death from any cause, assessed up to 12 months

• Incidence of Treatment-Related Adverse Events (TRAEs)

  From enrollment to 28 days after last study treatment

Study Arms (1)

Treatment

EXPERIMENTAL

Single arm: Neoadjuvant pucotenlimab + becotatug vedotin, then adjuvant pucotenlimab for surgical patients. Max 4 neoadjuvant cycles (Q3W): Day1 pucotenlimab 3mg/kg (max 200mg, 60min IV), ≥30min later becotatug vedotin 2.0mg/kg (60-90min IV). Therapy stops early for progression/unmanageable toxicity. Post-neoadjuvant MDT assessment for consolidative surgery. Resectable patients receive 17 cycles of adjuvant pucotenlimab 200mg Q3W.

Drug: Pucotenlimab plus Becotatug Vedotin

Interventions

Pucotenlimab plus Becotatug Vedotin DRUG

Neoadjuvant PD-1 inhibitor pucotenlimab (HX008) combine with EGFR ADC becotatug vedotin (MRG003) for locally advanced penile squamous cell carcinoma. Up to 4 Q3W neoadjuvant cycles; surgical patients receive 17-cycle adjuvant pucotenlimab.

Treatment

Eligibility Criteria

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

You may qualify if:

• Aged 18-75 years, biologically male.
• Histologically confirmed penile squamous cell carcinoma, stage T4 any N M0 or any T N2-N3 M0 without distant metastasis.
• Treatment-naive; or relapsed patients with ≥12 months interval from last prior systemic therapy.
• At least one measurable target lesion per RECIST 1.1.
• ECOG performance status 0-2.
• Adequate bone marrow, liver and renal function as predefined lab thresholds.
• Expected survival ≥12 months.
• No severe uncontrolled organ dysfunction.
• Able to understand and voluntarily sign written informed consent.

You may not qualify if:

• Pre-existing grade ≥2 peripheral neuropathy interfering daily activities.
• Prior neoadjuvant therapy for penile cancer; previous use of PD-1/PD-L1 inhibitors or EGFR ADCs including becotatug vedotin.
• Known hypersensitivity to pucotenlimab, becotatug vedotin or excipients.
• Active malignancy within 5 years (excluding cured basal cell skin carcinoma and low-risk prostate cancer).
• Uncontrolled severe cardiovascular disease, active hepatitis B/C, active infection requiring antibiotics within 2 weeks before enrollment.
• Live vaccine administered within 30 days before first dosing.
• HIV infection, autoimmune disease requiring systemic therapy within 2 years, long-term systemic immunosuppressants.
• Other conditions judged by investigators to interfere with study treatment or assessment.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Jiangsu Cancer Institute & Hospital: collaborator
• Hunan Cancer Hospital: collaborator
• West China Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• Tongji Hospital: collaborator
• The First Affiliated Hospital of Nanchang University: collaborator
• The Affiliated Tumor Hospital of Xinjiang Medical University: collaborator
• Tianjin Medical University Cancer Institute and Hospital: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, 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

Hui Han, MD, PhD

CONTACT

+86-020-8734-3860; hanhui@sysucc.org.cn

Longbin Xiong, MD

CONTACT

+86-020-8734-2318; xionglb@sysucc.org.cn

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: M.D., Ph.D.

Study Record Dates

• First Submitted: August 10, 2026
• First Posted: August 17, 2026
• Study Start: August 15, 2026
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): August 15, 2029
• Last Updated: August 17, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)