Phase 2 Study of MK-7684A (Pembrolizumab, Vibostolimab) With or Without Additional Anticancer Agents in Advanced Solid Tumors Expressing PD-L1

The primary objective of this study is to compare **MK-7684A** to pembrolizumab alone with respect to the **Objective Response Rate (ORR)** per RECIST 1.1, as assessed by Blinded Independent Central Review (BICR) in participants with cervical cancer whose tumors express PD-L1 (CPS ≥1) enrolled in Cohort A1. This comparison is clinically relevant as it aims to determine the efficacy of MK-7684A in improving response rates in a specific subset of cervical cancer patients, potentially offering a more effective treatment option.

Secondary objectives include:

• Evaluating MK-7684A alone or in combination with other anticancer therapies with respect to Overall Survival (OS) in participants with selected solid tumors.
• Assessing MK-7684A alone or in combination with other anticancer therapies with respect to Progression-Free Survival (PFS) per RECIST 1.1, excluding participants with cervical cancer whose tumors express PD-L1 (CPS ≥1) in Cohort A1.
• Evaluating MK-7684A alone with respect to Duration of Response (DOR) per RECIST 1.1 as assessed by BICR in participants with cervical cancer whose tumors express PD-L1 (CPS ≥1) in Cohort A1.
• Comparing MK-7684A to pembrolizumab alone with respect to PFS per RECIST 1.1 as assessed by the investigator in participants with cervical cancer whose tumors express PD-L1 (CPS ≥1) in Cohort A1.
• Evaluating change from baseline in Health-Related Quality of Life (HRQoL) using the EORTC QLQ-C30 in participants with cervical cancer whose tumors express PD-L1 (CPS ≥1) in Cohort A1.
• Evaluating the safety and tolerability of MK-7684A alone or in combination with other anticancer therapies.

The clinical trial involves a total of **410 participants** diagnosed with **advanced solid tumors**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on the presence of histologically or cytologically confirmed advanced solid tumors, such as squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, among others. The trial does not include a vulnerable population. Participants are required to have measurable disease per RECIST v1.1 and adequately controlled blood pressure. Those with HIV must have well-controlled infection on antiretroviral therapy. Lifestyle considerations include adherence to contraceptive guidance for both male and female participants, with females not being pregnant or breastfeeding. The trial population was selected to ensure adequate organ function among participants.

The clinical trial is designed as a **randomized**, open-label, Phase 2 basket study to evaluate the efficacy and safety of MK-7684A, a combination of **vibostolimab** and **pembrolizumab**, with or without other anticancer therapies in participants with selected **advanced solid tumors**. The trial aims to compare the objective response rate (ORR) and progression-free survival (PFS) of MK-7684A to pembrolizumab alone in participants with cervical cancer expressing PD-L1, as well as to evaluate the combination therapy in other solid tumors. The study is expected to run from October 18, 2021, to September 15, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically or cytologically confirmed advanced solid tumors, measurable disease per RECIST v1.1, and adequate organ function. Following the screening, participants will be randomized into treatment cohorts. Regular follow-up visits will be conducted to monitor treatment response, adverse events, and overall health status. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment.

The expected length of participant involvement varies depending on the treatment cohort, with a maximum treatment period of up to 245 days for certain therapies. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves several experimental and non-experimental treatments. **Capecitabine** is administered in the form of a pharmaceutical product coded as PHF00009MIG. It is an oral medication with a maximum daily dose of 2000 mg/m² and a total dose limit of 980,000 mg/m² over a treatment period of 105 days. The active substance is of chemical origin.

**Paclitaxel** is provided as a pharmaceutical product coded PHF00230MIG, administered via intravenous infusion. The maximum daily dose is 175 mg/m², with a total dose limit of 1200 mg/m² over 140 days. It is also of chemical origin.

**Gemcitabine Hydrochloride** is another intravenous infusion product coded PHF00230MIG. The maximum daily dose is 1000 mg/m², with a total dose limit of 70,000 mg/m² over 105 days. This substance is chemically derived.

**Carboplatin** is administered intravenously, with a pharmaceutical form coded PHF00230MIG. The maximum daily dose is 900 mg, with a total dose limit of 4500 mg over 15 days. It is of chemical origin.

**Lenvatinib** is provided in capsule form, with a maximum daily dose of 20 mg and a total dose limit of 4900 mg over 245 days. It is administered orally and is of chemical origin.

**Docetaxel** is administered via intravenous infusion, with a pharmaceutical form coded PHF00230MIG. The maximum daily dose is 75 mg/m², with a total dose limit of 375 mg/m² over 15 days. It is of chemical origin.

**Pembrolizumab**, marketed as KEYTRUDA, is a concentrate for solution for infusion. It is administered intravenously with a maximum daily dose of 200 mg and a total dose limit of 7000 mg over 105 days. It is a biological product.

**Fluorouracil** is administered via intravenous infusion, with a pharmaceutical form coded PHF00230MIG. The maximum daily dose is 800 mg/m², with a total dose limit of 140,000 mg/m² over 105 days. It is of chemical origin.

**Oxaliplatin** is administered intravenously, with a pharmaceutical form coded PHF00230MIG. The maximum daily dose is 130 mg/m², with a total dose limit of 4550 mg/m² over 105 days. It is of chemical origin.

**Cisplatin** is administered via intravenous infusion, with a pharmaceutical form coded PHF00015MIG. The maximum daily dose is 80 mg/m², with a total dose limit of 480 mg/m² over 18 days. It is of chemical origin.

**Bevacizumab** is administered intravenously, with a pharmaceutical form coded PHF00230MIG. The maximum daily dose is 15 mg/kg, with a total dose limit of 225 mg/kg over 45 days. It is a biological product.

**MK-7684A**, a combination of **Pembrolizumab** and **Vibostolimab**, is provided as a solution for infusion. It is administered intravenously with a maximum daily dose of 400 mg and a total dose limit of 14,000 mg over 105 days. It is a biological/vaccine product.

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include the **Objective Response Rate (ORR)** and **Progression-Free Survival (PFS)**, both evaluated per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. These assessments will be conducted by a Blinded Independent Central Review (BICR) and by investigators. The ORR will measure the proportion of participants with a predefined reduction in tumor size, while PFS will evaluate the time during which a participant's disease does not worsen. PFS will be specifically assessed at 9 and 12 months for certain cohorts.

Secondary endpoints include **Overall Survival (OS)**, the duration of response (DOR) per RECIST 1.1, and changes from baseline in global health status and physical functioning scores, as measured by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30). Additionally, the number of participants experiencing adverse events will be recorded. These endpoints will provide a comprehensive evaluation of the treatment's impact on both clinical outcomes and quality of life.