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.
