Primary Outcomes:

Primary Outcome 1 - Measure: Frequency of TEAEs (treatment-emergent adverse events)

Primary Outcome 1 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Primary Outcome 2 - Measure: Number of participants with DLTs (dose-limiting toxicities)

Primary Outcome 2 - Time Frame: Up to day 28

Primary Outcome 3 - Measure: Number of subjects with grade ≥3 TEAEs

Primary Outcome 3 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Primary Outcome 4 - Measure: Percentage of subjects with grade ≥3 TEAEs

Primary Outcome 4 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Primary Outcome 5 - Measure: Number of subjects with 1 or more SAEs (serious adverse events)

Primary Outcome 5 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Primary Outcome 6 - Measure: Percentage of subjects with 1 or more SAEs

Primary Outcome 6 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Primary Outcome 7 - Measure: Number of subjects with 1 or more TEAEs leading to dose modifications

Primary Outcome 7 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Primary Outcome 8 - Measure: Number of subjects with 1 or more TEAEs leading to treatment discontinuation

Primary Outcome 8 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Primary Outcome 9 - Measure: Percentage of subjects with 1 or more TEAEs leading to dose modifications

Primary Outcome 9 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Primary Outcome 10 - Measure: Percentage of subjects with 1 or more TEAEs leading to treatment discontinuation

Primary Outcome 10 - Time Frame: From the first dose until the last subject hast completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever comes first

Condition:

• Carcinoma, Non-Small-Cell Lung
• Urothelial Carcinoma
• Malignant Melanoma
• Head and Neck Squamous Cell Carcinoma

Eligibility

Criteria:
Inclusion Criteria:

- Subjects with metastatic or locally advanced, incurable non-small-cell lung cancer
(NSCLC [adenocarcinoma, adenosquamous, or squamous]), head and neck squamous cell
carcinoma (HNSCC), urothelial cancer, or malignant melanoma who have exhausted or
declined available standard therapy.

- Subjects progressing on previous treatment with a checkpoint inhibitor targeting
thePD-1/PD-L1 pathway, alone or in combination with chemotherapy after previously
having achieved stable disease or better and stayed on such therapy for ≥12 weeks.

- Primary or metastatic lesion suitable for biopsy and willingness to undergo repeat
biopsies as appropriate.

- Willing and able to provide intravenous access for the administration of the study
drug and for blood sampling/testing.

Exclusion Criteria:

- Subjects with NSCLC tumors with genetic alteration or mutation, for which FDA-approved
targeted therapy is available.

- Treatment with systemic anticancer treatments, investigational products, or major
surgery within 4 weeks before first dose of study drug or 5 half-lives, whichever is
shorter. Subjects should have recovered from previous treatment toxicity (except hair
loss and peripheral neuropathy).

- History of uncontrolled brain metastasis.

- Subject has received extended field radiotherapy ≤4 weeks before the start of
treatment (≤2 weeks for limited field radiation to alleviate symptoms), and who has
not recovered from related side effects of such therapy (except for hair loss).

- Subjects who have previously experienced an immune-related adverse event (irAE) to
pembrolizumab, for which permanent discontinuation is required. Subjects without a
formal contraindication due to previous irAE are not eligible if the AE has not
resolved or requires steroids (>10 mg prednisone-equivalent per day) for ongoing
management.

- Subjects with active severe infection requiring oral antibiotics.

- Clinical evidence of an active second invasive malignancy with the exception of stable
prostate cancer on watchful waiting.

- Uncontrolled or significant cardiovascular disease.

- History of autoimmune disease requiring systemic immunosuppressive therapy (daily
prednisone equivalent doses >10 mg/day).

- HIV patients can be enrolled if the infection is adequately controlled.

- Known bleeding disorder or coagulopathy. Subjects on stable anticoagulant therapy are
allowed.

- Known or suspected allergy to study treatment or related products.

- Women who are pregnant or breastfeeding, or trying to become pregnant.

- Patients with chronic viral hepatitis.

Other protocol-defined inclusion/exclusion criteria may apply.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No