Phase 2 Study of Pembrolizumab and Chemotherapy in Patients With Newly Diagnosed Classical Hodgkin Lymphoma (KEYNOTE-C11)

The primary objective of this study is to evaluate the **complete response (CR) rate** at the end of the study intervention in participants with newly diagnosed **Classical Hodgkin Lymphoma (cHL)**. This assessment is conducted by independent central review according to the Lugano 2014 response criteria. The clinical relevance of this objective lies in determining the efficacy of the treatment regimen in achieving a complete response, which is a critical endpoint in the management of cHL.

Secondary objectives include: - Evaluating the CR rate at the end of the study intervention in participants with newly diagnosed cHL by investigator assessment according to Lugano 2014 response criteria. - Evaluating the duration of complete response (DurCR) in participants with newly diagnosed cHL by independent central review according to Lugano 2014 response criteria. - Evaluating the rate of Positron Emission Tomography (PET) negativity at PET2 following 3 cycles of pembrolizumab monotherapy by independent central review according to the 2-flurodeoxyglucose (FDG)-PET 5-point scale. - Evaluating the rate of PET negativity at PET3 after completion of 3 cycles of pembrolizumab monotherapy followed by 2 cycles of doxorubicin in combination with vinblastine and dacarbazine (AVD) by independent central review according to the FDG-PET 5-point scale. - Evaluating the safety and tolerability of initial pembrolizumab monotherapy followed by chemotherapy and pembrolizumab consolidation in participants with newly diagnosed cHL.

The clinical trial involves a total of **96 participants** diagnosed with **Classical Hodgkin Lymphoma**. The study population includes both male and female subjects, with an age range that encompasses young adults to older adults. Participants were selected based on specific criteria, including a histologically confirmed diagnosis of Ann Arbor Stage III or IV Classical Hodgkin Lymphoma, with Stage I and II participants eligible if they possess at least one National Comprehensive Cancer Network unfavorable risk factor. All participants have measurable 2-fluorodeoxyglucose-avid disease and have not received prior radiation therapy, chemotherapy, immunotherapy, or other systemic therapy for the treatment of Classical Hodgkin Lymphoma before the study intervention. The trial includes individuals with an Eastern Cooperative Oncology Group Performance Status of 0 to 1, assessed within 7 days before the start of the study intervention. The trial population is noted to include vulnerable populations, and lifestyle considerations such as diet and physical activity are not specified by the sponsor.

The clinical trial is designed to evaluate the efficacy and safety of **pembrolizumab** in combination with chemotherapy in patients with newly diagnosed **Classical Hodgkin Lymphoma**. This is a Phase 2, randomized, double-blind, controlled trial. The trial aims to assess the complete response rate at the end of the study intervention, as evaluated by independent central review according to the Lugano 2014 response criteria. The trial is expected to run until December 31, 2024, with recruitment having started on November 8, 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histologically confirmed diagnosis of Ann Arbor Stage III or IV Classical Hodgkin Lymphoma, measurable 2-fluorodeoxyglucose (FDG)-avid disease, and an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. Following the screening, participants will receive the study intervention, which includes **pembrolizumab** and a combination of chemotherapeutic agents such as **doxorubicin**, **etoposide**, **vinblastine sulfate**, **bleomycin**, **vincristine**, **prednisolone**, **anhydrous cyclophosphamide**, **dacarbazine**, and **procarbazine**. These agents will be administered via intravenous infusion or orally, depending on the specific medication.

Throughout the trial, participants will attend regular follow-up visits to monitor their response to treatment and any adverse events. The primary endpoint is the complete response at the end of the study intervention, with secondary endpoints including the duration of complete response, PET negativity, and the number of participants experiencing adverse events or discontinuing treatment due to adverse events. The expected length of participant involvement is up to 33 months, depending on the treatment regimen and response. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or the participant's decision to withdraw consent.

The clinical trial involves the administration of several **experimental medications** to evaluate their efficacy in patients with newly diagnosed classical Hodgkin Lymphoma. The first medication, **Doxorubicin**, is administered as an intravenous infusion. It is provided in a pharmaceutical form identified as PHF00231MIG. The maximum daily dose is 35 mg/m², with a total maximum dose of 300 mg/m² over a treatment period of up to 24 weeks.

**Etoposide** is another experimental medication used in this trial, also administered via intravenous infusion. It is available in the pharmaceutical form PHF675. The maximum daily dose is 200 mg/m², with a total maximum dose of 1600 mg/m², and the treatment period is limited to 12 weeks.

**Vinblastine Sulfate** is included in the study, administered through intravenous infusion in the form PHF00231MIG. The maximum daily dose is 6 mg/m², with a total maximum dose of 72 mg/m² over a 24-week treatment period.

**Bleomycin** is administered as an intravenous infusion in the form PHF00231MIG. The maximum daily dose is 10 IU, with a total maximum dose of 40 IU, and the treatment period is 12 weeks.

**Vincristine** is also part of the trial, administered via intravenous infusion in the form PHF675. The maximum daily dose is 2 mg/m², with a total maximum dose of 8 mg/m² over a 12-week period.

**Prednisolone** is administered orally in the form PHF00245MIG. The maximum daily dose is 40 mg/m², with a total maximum dose of 2240 mg/m², and the treatment period is 12 weeks.

**Anhydrous Cyclophosphamide** is administered as an intravenous infusion in the form PHF00231MIG. The maximum daily dose is 1250 mg/m², with a total maximum dose of 5000 mg/m² over a 12-week period.

**Dacarbazine** is administered via intravenous infusion in the form PHF00230MIG. The maximum daily dose is 375 mg/m², with a total maximum dose of 4500 mg/m², and the treatment period is 24 weeks.

**Procarbazine** is administered orally in the form PHF00006MIG. The maximum daily dose is 100 mg/m², with a total maximum dose of 2800 mg/m² over a 12-week period.

**Pembrolizumab**, marketed as Keytruda, is administered as an intravenous infusion. It is provided as a concentrate for solution for infusion with a concentration of 25 mg/mL. The maximum daily dose is 200 mg, with a total maximum dose of 1400 mg over a treatment period of 33 weeks. This medication is classified as a biological product.

All medications are administered according to the specified dosing schedules, and participant compliance is monitored throughout the trial. The trial does not include any non-experimental treatments such as standard-of-care therapy or placebo. The study aims to assess the complete response rate at the end of the intervention, evaluated by independent central review according to the Lugano 2014 response criteria.

The efficacy of the clinical trial will be assessed primarily through the evaluation of the **Complete Response (CR)** rate at the end of the study intervention. This assessment will be conducted by an independent central review using the Lugano 2014 response criteria. Secondary endpoints include the CR rate as assessed by the investigator, the duration of complete response (DurCR), and the positron emission tomography (PET) negativity by independent central review per 2-fluorodeoxyglucose (FDG)-PET 5-point scale after the administration of pembrolizumab monotherapy and chemotherapy. Additionally, the number of participants who experienced an adverse event (AE) and those who discontinued study treatment due to an AE will be recorded.

The efficacy parameters will be measured and collected at the end of the study intervention. The assessments will be performed using validated criteria and scales, specifically the Lugano 2014 response criteria and the FDG-PET 5-point scale. The independent central review will ensure objectivity and consistency in the evaluation of the primary and secondary endpoints. The trial aims to provide comprehensive data on the efficacy of pembrolizumab in combination with chemotherapy in patients with newly diagnosed classical Hodgkin Lymphoma.