Phase 1/2 Study of Intravesical MK-3120 in BCG-Naïve or BCG-Exposed High-Risk Non-muscle Invasive Bladder Cancer

The primary objective is to evaluate the safety and tolerability of intravesical MK-3120 monotherapy in patients with high-risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. This assessment is clinically relevant for determining the acceptable toxicity profile of this novel intravesical suspension containing SKB410 in both BCG-naïve and BCG-exposed patient populations.

The secondary objective is to evaluate the efficacy of intravesical MK-3120 with respect to complete response rate (CRR) at 3 months based on local assessment. This endpoint provides early clinical evidence of therapeutic activity in this patient population with high-risk bladder malignancy.

This clinical trial enrolled a total of **14 participants** diagnosed with **high-risk non-muscle invasive bladder cancer (NMIBC)** with **carcinoma in situ (CIS)** with or without papillary tumors. The study population included both **male and female** adults and elderly individuals. Participants were required to have histologically confirmed CIS with or without papillary high-risk NMIBC, confirmed locally. Eligible individuals must have undergone **transurethral resection of bladder tumor (TURBT)** within 12 weeks before allocation, with complete resection of all papillary tumors when present. The trial included two distinct groups: **Bacillus Calmette-Guérin (BCG)-naïve** participants who either never received BCG or had received it more than 2 years before disease recurrence with evidence of complete response during the 2-year post-BCG period, and **BCG-exposed** participants who received adequate BCG therapy and experienced recurrence more than 12 months but not exceeding 24 months after the last BCG dose. Participants with controlled **human immunodeficiency virus (HIV)** infection on antiretroviral therapy were eligible for enrollment. Individuals positive for **hepatitis B surface antigen** could participate if they had received **hepatitis B virus (HBV)** antiviral therapy for at least 4 weeks with undetectable HBV viral load prior to allocation. Participants with a history of **hepatitis C virus (HCV)** infection were eligible if HCV viral load was undetectable at screening.

This is a Phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of intravesical MK-3120 monotherapy in participants with high-risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. The investigational medicinal product, MK-3120, is a biological agent containing the active substance SKB410, administered as an intravesical suspension. The trial employs an integrated Phase 1/2 design to assess dose-limiting toxicities, adverse events, and treatment discontinuations due to adverse events as primary endpoints, with complete response rate as the secondary endpoint. The study is designed to enroll participants who are either Bacillus Calmette-Guérin (BCG)-naïve or BCG-exposed, meeting specific criteria regarding their BCG treatment history and disease recurrence patterns.

Eligible participants must have histologically confirmed carcinoma in situ with or without papillary high-risk NMIBC, confirmed locally. The most recent transurethral resection of bladder tumor (TURBT) must have been performed within 12 weeks before allocation, demonstrating high-risk NMIBC histology. For participants with papillary tumors, complete TURBT with visually complete resection of all papillary tumors must have been achieved. BCG-naïve participants are defined as those who have never received BCG or received BCG more than 2 years before CIS recurrence with evidence of complete response during the 2-year period post-BCG. BCG-exposed participants must have received adequate BCG therapy and experienced recurrence of CIS with or without papillary high-risk NMIBC more than 12 months but no more than 24 months after the last BCG dose. Participants with human immunodeficiency virus (HIV) infection are eligible if they have well-controlled HIV on antiretroviral therapy. Those who are hepatitis B surface antigen positive may participate if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to allocation. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

The estimated recruitment start date is December 2025, with an estimated trial completion date of February 2029. The overall trial duration encompasses the period required for participant enrollment, treatment administration, and follow-up assessments to evaluate safety, tolerability, and efficacy outcomes. Participants who discontinue study treatment due to adverse events will be withdrawn from the trial. The trial design includes systematic monitoring of dose-limiting toxicities and adverse events throughout the treatment period to ensure participant safety and inform dose selection for subsequent phases of the study.

The experimental medicinal product in this clinical trial is **MK-3120**, a biological agent containing the active substance **SKB410**, which is classified as a protein. The product is formulated as an **intravesical suspension** for direct administration into the bladder via **intravesical use**. MK-3120 is administered as monotherapy in participants with **BCG-naïve** or **BCG-exposed high-risk non-muscle invasive bladder cancer**. The study is designed to evaluate the safety and tolerability of this investigational treatment. The pharmaceutical form allows for local delivery of the active substance directly to the bladder mucosa, which is the intended site of therapeutic action in this patient population.

The source data does not provide specific information regarding the exact dosage amounts, frequency of administration, duration of treatment cycles, or specific dosing schedules for MK-3120. Additionally, no information is available regarding the use of placebo, comparator treatments, or standard-of-care therapies in this trial. Details concerning participant compliance monitoring procedures are not specified in the provided documentation.

Efficacy will be assessed through the evaluation of Complete Response Rate (CRR) as a secondary endpoint in this clinical trial. The complete response rate will serve as a measure of treatment effectiveness in participants with high-risk non-muscle invasive bladder cancer. This endpoint will provide data on the proportion of participants achieving complete resolution of disease following treatment with intravesical MK-3120 monotherapy.