QL1706 Plus Lenvatinib in Previously Treated Penile Cancer

Phase 2RecruitingNCT07384416

Sun Yat-sen University47 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Penile Cancer

Interventions

QL1706 + LenvatinibDRUG

Lenvatinib: 8 mg once daily (for body weight \<60 kg) or 12 mg once daily (for body weight ≥60 kg). QL1706: 5 mg/kg, administered by intravenous infusion (iv) on Day 1 of each cycle. Treatment Cycle: Each cycle is 21 days. 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.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

median PFS (median Progression-Free Survival）

defined as the median time from study enrollment to the first occurrence of any of the following events: Radiographic disease progression according to RECIST version 1.1, as determined by the investigator; For patients who undergo conversion surgery, postoperative local recurrence or distant metastasis; Death from any cause, whichever occurs first. Conversion surgery itself will not be considered a PFS event. For participants who have not experienced a PFS event at the time of analysis, PFS will be censored at the date of the last tumor assessment or last follow-up.

Time frame: From treatment initiation date to first documented disease progression or death from any cause

Secondary Outcomes

ORR (Objective Response Rate）

Time frame: Baseline to first documented disease progression, death or last valid tumor assessment

Disease Control Rate

The proportion of participants who achieve complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1 criteria.

Time frame: From baseline until the earliest documented disease progression, death from any cause, or the last valid tumor assessment without prior progression.

Duration of Response

The time interval from the first documentation of confirmed CR or PR to the earliest documented disease progression or death from any cause.

Time frame: Time Frame: From date of first confirmed CR/PR until first documented disease progression or death

median overall survival

Median Overall Survival (OS) is defined as the median time interval from the date of treatment initiation to the date of death from any cause. For participants who were alive at the last follow-up or lost to follow-up, OS was censored at the date of the last known alive status.

Time frame: From treatment initiation date to death from any cause

Adverse Event Rate

The proportion of participants who experience at least one adverse event during the study treatment period and follow-up period

Time frame: From treatment initiation through 30 days after the last study drug administration