Evaluation of Nivolumab Monotherapy and Nivolumab-Ipilimumab Combination in Advanced or Metastatic Solid Tumors: A Phase 1/2 Open-label Study

The primary objective of this study is to investigate the **safety** and efficacy of **Nivolumab** as a monotherapy or in combination with **Ipilimumab** in subjects with advanced or metastatic solid tumors, specifically targeting six tumor types: triple-negative breast cancer, gastric cancer, pancreatic adenocarcinoma, small cell lung cancer, bladder cancer, and ovarian cancer. This is clinically relevant as it aims to evaluate the potential of these immunotherapies in treating various aggressive cancers, potentially leading to improved therapeutic strategies.

Secondary objectives include evaluating the following parameters:

• **BOR** (Best Overall Response)
• **DOR** (Duration of Response)
• **Safety**
• **PFS** (Progression-Free Survival)
• **OS** (Overall Survival)

These secondary objectives are crucial for understanding the broader impact of the treatment on patient outcomes, including response durability and overall survival benefits.

The clinical trial involves a total of **1620 participants** diagnosed with advanced or metastatic solid tumors, specifically targeting six types: **Triple Negative Breast Cancer (TNBC)**, Gastric Cancer (GC), Pancreatic Cancer (PC), Small Cell Lung Cancer (SCLC), Bladder Cancer (BC), and Ovarian Cancer (OC). The study population includes both male and female subjects, with an age range that spans from young adults to the elderly. Participants were selected based on the presence of histologically confirmed locally advanced or metastatic disease in the specified tumor types, and they must have measurable disease with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The trial does not include vulnerable populations. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The selection criteria ensure a focus on individuals with a confirmed diagnosis of the targeted cancers, allowing for a comprehensive evaluation of the safety and efficacy of Nivolumab, either as a single agent or in combination with Ipilimumab.

The clinical trial is designed as a **Phase 1/2**, open-label study to evaluate the safety and efficacy of **nivolumab** monotherapy or in combination with **ipilimumab** in subjects with advanced or metastatic solid tumors, including triple-negative breast cancer, gastric cancer, pancreatic cancer, small cell lung cancer, bladder cancer, and ovarian cancer. The trial employs a non-randomized, open-label design, allowing for the direct observation of treatment effects without the use of a placebo or control group. The estimated duration of the trial spans from October 30, 2013, to October 31, 2024, encompassing both recruitment and follow-up periods.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed locally advanced or metastatic disease and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Following the screening, participants will receive treatment with either nivolumab alone or in combination with ipilimumab, administered intravenously as a concentrate for solution for infusion. Regular follow-up visits will be scheduled to monitor the objective response rate (ORR), treatment-related adverse events, progression-free survival (PFS), and overall survival (OS). The end-of-study visit will conclude the participant's involvement, assessing the final outcomes and any long-term effects of the treatment.

The expected length of participant involvement will vary depending on individual response and tolerance to the treatment, with conditions for early termination including significant adverse events or disease progression. Participants may be withdrawn from the study if they experience treatment-related adverse events leading to drug discontinuation within the first 12 weeks. The trial aims to provide valuable insights into the therapeutic potential of nivolumab and ipilimumab in treating various advanced or metastatic solid tumors, contributing to the broader understanding of their safety and efficacy profiles.

The clinical trial involves the administration of **Nivolumab**, marketed under the name OPDIVO, which is a **concentrate for solution for infusion**. This experimental medication is provided at a concentration of 10 mg/mL and is administered via the **intravenous** route. The frequency and specific dosing schedule are determined based on the study protocol, which aims to evaluate the safety and efficacy of Nivolumab as a monotherapy or in combination with another investigational drug. The pharmaceutical form is specifically designed for infusion, ensuring precise delivery of the active substance, which is a protein of non-human origin. Compliance with the administration schedule is monitored throughout the trial to ensure adherence to the protocol.

In combination therapy arms of the study, **Ipilimumab** is also administered. Ipilimumab is provided as a **concentrate for solution for infusion** and is delivered intravenously. The product is identified by the sponsor product code BMS734016 and is also known by the alternative name MDX-010. The active substance, Ipilimumab, is a protein of non-human origin, similar to Nivolumab. The dosing regimen for Ipilimumab is aligned with the study's objectives to assess its combined effect with Nivolumab in treating advanced or metastatic solid tumors. Participant compliance with the dosing schedule is rigorously monitored to ensure the integrity of the trial data.

No non-experimental treatments, such as standard-of-care therapy or placebo, are specified in the trial documentation. The study focuses on the investigational use of Nivolumab and Ipilimumab, both of which are provided by Bristol-Myers Squibb. The trial is designed to explore the therapeutic potential of these agents in various cancer types, including triple-negative breast cancer, gastric cancer, pancreatic adenocarcinoma, small cell lung cancer, bladder cancer, and ovarian cancer. The administration of these drugs is conducted under strict clinical conditions to ensure participant safety and the collection of reliable efficacy data.

The efficacy of the clinical trial will be assessed using the **Objective Response Rate (ORR)** as the primary endpoint. ORR is defined as the number of subjects with a confirmed best overall response of complete response or partial response, divided by the number of assigned subjects. This will be determined by the investigators for all assigned subjects. Secondary endpoints include the rate of treatment-related adverse events leading to drug discontinuations during the first 12 weeks of treatment, **Progression-Free Survival (PFS)**, and **Overall Survival (OS)**. These parameters will provide a comprehensive evaluation of the treatment's efficacy in subjects with advanced or metastatic solid tumors, including triple-negative breast cancer, gastric cancer, pancreatic adenocarcinoma, small cell lung cancer, bladder cancer, and ovarian cancer.