Overview

This phase II clinical study aims to evaluate the efficacy and safety of QL1706 in combination with lenvatinib in patients with previously treated advanced or metastatic penile squamous cell carcinoma.

The primary objective of the study is to determine the median progression-free survival (PFS) of this regimen according to RECIST 1.1 criteria. Secondary objectives include evaluating objective response rate, disease control rate, overall survival, duration of response, safety, and the rate of conversion surgery.

All enrolled participants will receive QL1706 plus lenvatinib as induction therapy for up to four treatment cycles (21 days per cycle). After completion of four cycles, tumor response will be assessed by imaging and multidisciplinary team (MDT) evaluation. Patients whose tumors become resectable and who are considered likely to benefit from surgery may undergo conversion surgery. Patients who are not eligible for surgery will continue study treatment.

Following induction therapy or surgery, participants may continue QL1706 plus lenvatinib as continuation therapy. QL1706 will be administered for up to one year, and lenvatinib will be continued until disease progression according to RECIST 1.1, unacceptable toxicity, withdrawal of consent, or investigator decision.

Tumor assessments will be performed using imaging studies such as CT or MRI at scheduled intervals. Safety will be monitored through clinical evaluations, laboratory testing, and adverse event reporting throughout the study.

Eligibility

Inclusion Criteria:

1. Age between 18 and 80 years.
2. Histologically or cytologically confirmed penile squamous cell carcinoma.
3. Previous treatment with chemotherapy, immunotherapy, and/or targeted therapy.
4. At least one measurable target lesion according to RECIST 1.1 criteria.
5. ECOG performance status score of ≤ 2.
6. Adequate bone marrow function: Hemoglobin (Hb) ≥ 75 g/L, White Blood Cell count (WBC) ≥ 3.0×10⁹/L, Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L, Platelet count (PLT) ≥ 100×10⁹/L.
7. Adequate organ function:

   Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline Phosphatase (ALP) ≤ 2.5 times the upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN.

   Serum creatinine ≤ 1.5 × ULN.

8. Life expectancy of ≥ 12 months.
9. No significant history of severe cardiac, pulmonary, hepatic, or other major organ diseases.
10. The patient understands the study procedures and provides written informed consent to participate in the study.

Exclusion Criteria:

1. Participation in any investigational drug study within 4 weeks prior to the start of treatment.
2. Concurrent active cancer other than penile squamous cell carcinoma, or a history of other malignancies within the past 5 years, except for the following:
   • (1) Cured non-melanoma skin cancer;
   • (2) Incidentally discovered, low-risk, and curative tumors, including but not limited to low-risk prostate cancer (T1a, Gleason score \<6, PSA \<0.5 ng/ml) and superficial bladder cancer;
   • (3) Other solid tumors that have undergone curative treatment with no evidence of recurrence or metastasis for 5 years or more.
3. Other serious, poorly controlled concurrent illnesses that may be aggravated by the combination therapy, including but not limited to:
   • (1) History of severe or acute exacerbation within the past 6 months involving the cardiovascular, hepatic, respiratory, renal, hematological, endocrine, or neuropsychiatric systems;
   • (2) Active infection requiring antibiotic treatment within 2 weeks prior to enrollment;
   • (3) Congestive heart failure (Class III-IV);
   • (4) Unstable angina or myocardial infarction within the past 6 months;
   • (5) Untreated active Hepatitis B virus (HBV) infection. \Note: Subjects with HBV meeting the following criteria are eligible: HBV viral load must be \<1000 copies/ml (200 IU/ml) before the first dose, and the subject must receive anti-HBV therapy throughout the study treatment period to prevent reactivation. Subjects who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-) do not require prophylactic anti-HBV therapy but require close monitoring for reactivation.\
   • (6) Active Hepatitis C virus (HCV) infection (HCV antibody positive and HCV-RNA level above the limit of detection).
4. Administration of a live vaccine within 30 days prior to the first dose (Cycle 1, Day 1). \Inactivated seasonal influenza vaccines administered by injection are permitted within 30 days prior to the first dose; however, live attenuated influenza vaccines administered intranasally are not permitted.\
5. Diagnosis of immunodeficiency or receipt of systemic corticosteroid therapy (\>10 mg/day prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first study dose. \Physiologic doses of corticosteroids (≤10 mg/day prednisone or equivalent) are permitted.\
6. History of Human Immunodeficiency Virus (HIV) infection (i.e., positive HIV1/2 antibody test).
7. Systemic treatment with Chinese herbal medicines with anti-tumor indications or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use to control pleural effusion) within 2 weeks prior to enrollment.
8. Active autoimmune disease that has required systemic treatment (e.g., with disease-modifying agents, corticosteroids, or immunosuppressants) within the past 2 years.
9. Any other history, disease, concurrent condition, therapy, or laboratory abnormality that, in the investigator's judgment, might compromise the results, interfere with the subject's full participation throughout the study, or make the subject unsuitable for study participation.