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

Plain English Summary

EGFR-ADC (Becotatug Vedotin) Combined With PD-1 Inhibitor (Pucotenlimab) in Neoadjuvant Treatment of Advanced Penile Cancer is a Phase 2 clinical trial sponsored by Jiyan Liu studying Penile Cancer. This trial tests a new combination of two drugs, Becotatug Vedotin and Pucotenlimab, to shrink advanced penile cancer before surgery. It is for men aged 18 and older with penile squamous cell carcinoma that is difficult to treat with surgery or has spread to lymph nodes. Participants will receive intravenous infusions of the study drugs for 4-6 cycles, followed by surgery, and potentially more treatment. Alternative treatments may include standard chemotherapy, radiation, or surgery alone, depending on the cancer's stage and location. The trial aims to enroll 60 participants.

Official 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

Who Can Participate

Here is what you need to know about eligibility for this trial. Men aged 18 or older with a confirmed diagnosis of penile squamous cell carcinoma. Patients whose cancer is difficult to treat with surgery that preserves the penis or has spread to nearby lymph nodes. Individuals whose cancer cells show a specific protein called EGFR, which is targeted by one of the study drugs. Those who have not received prior systemic cancer treatment, or whose cancer recurred more than 6 months after previous treatment. This trial is studying Penile Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures whether the combination therapy allows for successful surgical removal of the cancer, which is crucial for long-term survival and quality of life. The specific primary outcome measures are: Surgical Resection Rate (Up to 6 months after the start of neoadjuvant therapy (after completion of 4-6 cycles of treatment and MDT evaluation).). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for more effective neoadjuvant treatments for advanced penile cancer, aiming to improve surgical outcomes and preserve penile function. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Penile Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a rare but aggressive cancer, with potential for a novel combination therapy to improve outcomes, signaling an opportunity in a niche oncology market. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of this new combination therapy compared to standard treatments. Understand that participation involves regular clinic visits for drug infusions, imaging scans, and blood tests. Be prepared for potential surgery after the initial treatment phase, and possibly further treatment afterward. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 60 participants

Interventions

• DRUG: Becotatug Vedotin — 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.
• DRUG: Pucotenlimab — 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.

Primary Outcomes

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

Secondary Outcomes

• 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.)

Full Eligibility Criteria

1. Inclusion Criteria （1）Histologically/cytologically confirmed penile squamous cell carcinoma (PSCC); （2）EGFR expression (IHC 1+, 2+, or 3+) confirmed by local pathology department; （3）No prior systemic therapy, or recurrence ≥6 months after adjuvant therapy for radical resection; （4）Male, aged ≥18 years; （5）Cytologically positive or clinically palpable inguinal lymphadenopathy, fixed mass, radiologically diagnosed pelvic lymph node metastasis, or penile preservation difficulty (unable to perform surgery with negative margin and functional penile stump preservation); （6）At least one measurable lesion per RECIST 1.1; （7）Adequate organ function:

   * 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.
2. Exclusion Criteria （1）Prior systemic therapy (except recurrence ≥6 months after adjuvant chemotherapy for radical resection); （2）Severe concurrent diseases or poor physical condition unsuitable for treatment/surgery (e.g., severely ulcerated/infected inguinal lymph nodes with high risk of poor wound healing); （3）Uncontrolled comorbidities: uncontrolled infection, active tuberculosis, uncontrolled diabetes, cardiovascular diseases (NYHA class III/IV heart failure, ≥grade 2 heart block, myocardial infarction within 12 months, unstable arrhythmia/angina, cerebral infarction within 6 months), interstitial lung disease, deep vein thrombosis/pulmonary embolism within 12 months, decompensated cirrhosis; （4）Active autoimmune diseases requiring systemic treatment within 2 years (except physiological replacement therapy); （5）Positive serological tests: HIV positive; HBsAg positive with HBV DNA ≥2000 copies/mL; HCV antibody positive with positive HCV RNA; （6）Major surgery within 4 weeks prior to enrollment, prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation; （7）Vaccination with anti-tumor vaccine within 4 weeks prior to enrollment or planned during the study; （8）Other conditions deemed unsuitable by the investigator.

Trial Locations

• West China Hospital of Sichuan University, Chengdu, Sichuan, China

Frequently Asked Questions

Related Conditions

• Penile Cancer
• Squamous Cell Carcinoma
• Genitourinary Cancers
• Oncology
• Targeted Therapy
• Immunotherapy
• Neoadjuvant Therapy
• Metastatic Cancer
• Lymph Node Metastasis
• EGFR-positive Cancers

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