Metastatic Penile Squamous Cell Carcinoma, Penile Squamous Cell Carcinoma
Conditions
Keywords
advanced/metastatic penile squamous cell carcinoma
Brief summary
This is a single-arm, Phase 2 clinical trial (PERSEUS TRIAL / LACOG 1924) evaluating the efficacy, safety, and tolerability of sacituzumab tirumotecan (sac-TMT; MK-2870) as a second-line treatment for patients with advanced or metastatic penile cancer. Penile squamous cell carcinoma (PSCC) is a rare and aggressive cancer with limited treatment options once disease progression occurs after initial platinum-based chemotherapy. Sacituzumab tirumotecan is an antibody-drug conjugate (ADC) designed to target TROP-2, a protein frequently expressed at high levels on penile cancer cells. By binding to TROP-2, sac-TMT delivers a anti-cancer payload directly to the tumor cells. All participants in this trial will receive sacituzumab tirumotecan administered via intravenous (IV) infusion every 2 weeks. The main goal of this study is to determine the percentage of patients whose tumors shrink or disappear after receiving sacituzumab tirumotecan (Objective Response Rate).
Detailed description
Penile squamous cell carcinoma (PSCC) represents a significant unmet medical need, particularly in low- and middle-income regions where the incidence is higher. For patients with disease recurrence or metastasis following first-line platinum-based chemotherapy, standard second-line therapeutic options offer poor response rates and a dismal median overall survival of 4 to 5 months. Recent findings show that over 80% of PSCC cases express high levels of TROP-2, making it a key therapeutic target. Sacituzumab tirumotecan (sac-TMT; MK-2870) is a novel antibody-drug conjugate (ADC) composed of a humanized anti-TROP2 monoclonal antibody linked to a topoisomerase I inhibitor payload (KL610023). Study Design & Intervention: This is an open-label, multicenter, single-arm Phase 2 trial enrolling 37 adult patients with advanced/metastatic PSCC who experienced disease progression on or after first-line platinum-based chemotherapy. Participants receive sacituzumab tirumotecan at a dose of 4 mg/kg via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle for up to 8 cycles, or until disease progression, unacceptable toxicity, or consent withdrawal. Primary Endpoint: Objective Response Rate (ORR), defined as the proportion of participants achieving a confirmed Complete Response (CR) or Partial Response (PR) assessed by the investigator using RECIST v1.1 criteria. Secondary Endpoints:Independent Central Review Objective Response Rate (ORR-ICR) Disease Control Rate (DCR) and Clinical Benefit Rate (CBR at 24 weeks) Duration of Response (DoR) Progression-Free Survival (PFS) and Overall Survival (OS) Safety and toxicity profile (evaluated via CTCAE v5.0) Treatment compliance and post-progression therapies Exploratory Research: Assessment of baseline tumor TROP-2 expression, HPV16 status, ctDNA dynamics, and molecular mechanisms of acquired resistance. Statistical Design: The trial utilizes Simon's two-stage Minimax design (18 participants accrued in Stage 1, expanding to 33 total evaluable participants if $\\ge5$ responses are observed). Accounting for a 10% drop-out rate, a total of 37 participants will be enrolled.
Interventions
DRUGSacituzumab Tirumotecan
Sacituzumab tirumotecan is an ADC consisting of 3 major components: 1) a humanized antihuman TROP2 mAb of IgG1 class; 2) an ADC-coupling linker with a methyl sulfonyl moiety as the leaving group; and 3) a cytotoxic drug in the class of topoisomerase 1 inhibitors, KL610023. The drug-antibody ratio of sacTMT is 7.4. Sacituzumab tirumotecan is designed to enhance the binding between the antibody and linker, which can prolong the half-life of ADC molecules in serum.
Sponsors
Latin American Cooperative Oncology Group
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A single-arm, multicenter Phase II trial evaluating sacituzumab tirumotecan (sac-TMT; MK-2870) in participants with advanced/metastatic penile squamous cell carcinoma whose disease progressed on or following platinum-based chemotherapy. All enrolled participants are assigned to receive the single study intervention.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically- or cytologically confirmed diagnosis of penile squamous cell carcinoma. * Metastatic or locally advanced disease not amenable to curative intent-therapy (e.g., surgery, radiotherapy, chemoradiotherapy) in the opinion of the investigator. * Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology (lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions). * Disease progression on first-line platinum-based chemotherapy for locally advanced/metastatic disease or disease progression within 12 months of (neo) adjuvant chemotherapy completion. * Male participant at least 18 years of age at the time of providing informed consent. * Male Participants (Reproductive Potential): If capable of producing sperm, agrees to refrain from donating sperm and use a penile/external condom when having intercourse with a partner of childbearing potential, plus partner use of an additional contraceptive method, during the intervention period and for at least 120 days after the last dose of study intervention. * The participant (or legally acceptable representative if applicable) provides written informed consent for the study. * Life expectancy of at least 12 weeks. * Provide an archival tumor tissue sample or most recently obtained core, incisional, or excisional biopsy of a tumor lesion from any site not previously irradiated; formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides (recommended 22-28 slides). * Recovery from AEs due to previous anticancer therapies to Grade \<=1 or baseline (except for alopecia and vitiligo); participants with endocrine-related AEs adequately treated with hormone replacement therapy are eligible. * Adequate organ function defined by the laboratory values (specimens collected within 14 days before the start of study intervention): * Absolute Neutrophil Count (ANC) \>= 1,500/uL * Platelets \>= 100,000/uL * Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L * Measured or calculated Creatinine Clearance \> 30 mL/min * Total Bilirubin \<= 1.5 x ULN OR direct bilirubin \< ULN for participants with total bilirubin levels \> 1.5 x ULN * AST (SGOT) and ALT (SGPT) \<= 2.5 x ULN (\<= 5 x ULN for participants with liver metastases) * Serum Albumin \>= 3.0 g/dL * INR or PT \< 1.5 x ULN; aPTT \< 1.5 x ULN (unless receiving anticoagulant therapy within therapeutic range) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Willing and able to comply with study procedures, laboratory tests, and other requirements of the study. * HIV-infected participants are eligible if well-controlled on ART (CD4+ T-cell count \>350 cells/mm3, confirmed HIV RNA \<50 copies/mL for at least 12 weeks, no AIDS-defining opportunistic infections within past 12 months, and on a stable regimen for at least 4 weeks without strong CYP3A4 inducers/inhibitors). * Participants with chronic Hepatitis B virus (HBsAg positive) are eligible if received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load before enrollment. * Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening and completed curative antiviral therapy at least 4 weeks before enrollment.
Exclusion criteria
* History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing. * Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea). * Uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months before first dose (NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, or QTcF \>480 ms). * Received prior treatment with a TROP2-targeted antibody-drug conjugate (ADC). * Received prior treatment with a topoisomerase 1 inhibitor-containing ADC. * Received prior systemic anticancer therapy within 2 weeks before first dose of study intervention. * Received prior radiotherapy within 2 weeks before first dose, has radiation-related toxicities requiring corticosteroids, and/or has had radiation pneumonitis (palliative radiotherapy \<= 2 weeks for non-CNS disease completed at least 7 days before first dose is permitted). * Received a live or live-attenuated vaccine within 30 days before first dose of study intervention. * Currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued (washout period required is 2 weeks). * Currently enrolled on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy. * Received an investigational agent or used an investigational device within 4 weeks before first dose of study intervention. * Known additional malignancy that is progressing or has required active treatment within the past 3 years (except adequately treated basal/squamous cell skin cancer, carcinoma in situ, or low-risk early-stage prostate cancer). * History of CNS metastases and/or carcinomatous meningitis. * Active infection requiring systemic therapy within 4 weeks prior to first dose of study treatment (except permitted treated HIV, HBV, HCV). * Severe hypersensitivity (Grade \>=3) to study intervention, any of its excipients, and/or to another biologic therapy. * Major surgery or significant traumatic injury within 4 weeks before first dose, or anticipation of need for major surgery during treatment. * History of (noninfectious) pneumonitis/interstitial lung disease requiring steroids or current pneumonitis/interstitial lung disease. * Any condition, therapy, laboratory abnormality, or circumstances that might confound study results or interfere with compliance in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Investigator Assessment | Up to 8 cycles (each cycle is 28 days) | Percentage of participants who achieve a confirmed Complete Response (CR) or Partial Response (PR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate by Independent Central Review (ORR-ICR) | Up to 8 cycles (each cycle is 28 days) | Percentage of participants who achieve a confirmed CR or PR as assessed by Independent Central Review using RECIST v1.1. |
| Disease Control Rate (DCR) | Up to 8 cycles (each cycle is 28 days) | Percentage of participants who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD) as assessed by the investigator using RECIST v1.1 |
| Clinical Benefit Rate (CBR) | At 24 weeks | Percentage of participants who achieve CR, PR, or SD lasting for at least 24 weeks from enrollment, as assessed by the investigator using RECIST v1.1. |
| Duration of Response (DoR) | Up to 36 months | Time from the first documented evidence of confirmed response (CR or PR) until disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first. |
| Progression-Free Survival (PFS) | Up to 36 months | Time from the date of enrollment until the first documented disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to 36 months | Time from the date of enrollment to the date of death due to any cause. |
| Incidence and Severity of Adverse Events (Safety and Toxicity) | From baseline up to 30 days after the last dose of study intervention. | Rate of overall treatment-emergent adverse events (TEAEs) and Grade 3 or higher adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. |
| Treatment Compliance | Up to 8 cycles (each cycle is 28 days) | Number and percentage of participants whose treatment was reduced, delayed, or permanently discontinued, categorized by reason (e.g., tumor progression, adverse events, or withdrawal of consent). |
| Post-Progression Therapies | Up to 36 months | Descriptive summary of subsequent anti-cancer therapies administered after disease progression on sacituzumab tirumotecan. |
Countries
Brazil
Contacts
CONTACTProject Manager
CONTACTHead of Operations
PRINCIPAL_INVESTIGATORFernando Cotait Maluf
Hospital Beneficência Portuguesa de São Paulo and Hospital Israelita Albert Einstein
PRINCIPAL_INVESTIGATORKarine Martins da Trindade
Instituto D'Or de Pesquisa e Ensino
Outcome results
None listed