Evaluation of Lorigerlimab and Docetaxel Versus Docetaxel Monotherapy in Metastatic Castration-Resistant Prostate Cancer Patients

The primary objective of this study is to evaluate the efficacy of **lorigerlimab** combined with **docetaxel** versus docetaxel alone, as measured by radiographic progression-free survival (rPFS) in participants with metastatic castration-resistant prostate cancer. This is clinically relevant as rPFS is a critical endpoint in assessing the effectiveness of cancer therapies, providing insights into the treatment's ability to delay disease progression.

Secondary objectives include:

• Evaluating the efficacy of lorigerlimab+docetaxel versus docetaxel as measured by objective response assessments.
• Assessing efficacy based on prostate-specific antigen (PSA) levels.
• Characterizing the safety and tolerability profile of lorigerlimab+docetaxel compared to docetaxel.
• Evaluating efficacy as measured by overall survival (OS).
• Characterizing the pharmacokinetics (PK) of lorigerlimab.
• Characterizing the immunogenicity of lorigerlimab.
• Evaluating quality of life (QOL) outcomes associated with lorigerlimab+docetaxel versus docetaxel, as measured by disease-related symptoms and participant-reported outcomes.

The clinical trial involves a total of **58 male participants** diagnosed with **Metastatic Castration-Resistant Prostate Cancer**. The study population is composed of adult males, specifically within the age ranges of 18 to 64 years and 65 years and older. Participants were selected based on specific inclusion criteria, including having metastatic castration-resistant adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell, or small cell features, and evidence of disease progression after prior androgen receptor axis-targeted therapy. Additionally, those with a known history of a documented breast cancer gene mutation must have received a poly ADP ribose polymerase inhibitor regimen. The trial does not include female subjects or vulnerable populations. Participants are required to have an adequate performance status, life expectancy, and laboratory values. Lifestyle factors such as diet and physical activity are not specified in the trial data provided.

The clinical trial is a **Phase 2**, randomized, open-label study designed to evaluate the efficacy of lorigerlimab in combination with **docetaxel** compared to docetaxel alone in participants with **metastatic castration-resistant prostate cancer**. The primary objective is to assess the median radiographic progression-free survival (rPFS) as determined by investigator review. Secondary endpoints include objective response rate (ORR), duration of response (DoR), time to response (TTR), PSA response rates, overall survival (OS), and various pharmacokinetic parameters of lorigerlimab. The trial is expected to conclude by September 2027, with recruitment having commenced in September 2023.

Participants will be randomly assigned to receive either the combination therapy or docetaxel alone. The study involves several key visits: an initial screening visit to confirm eligibility based on criteria such as the presence of metastatic lesions and prior treatment history, followed by regular follow-up visits to monitor treatment response and safety. The end-of-study visit will assess the final outcomes and any long-term effects. The expected duration of participant involvement is up to 30 days for the treatment period, with additional time for follow-up assessments.

Inclusion criteria require participants to have a confirmed diagnosis of metastatic castration-resistant adenocarcinoma of the prostate, with evidence of disease progression and prior treatment with androgen receptor axis-targeted therapy. Exclusion criteria are not specified in the provided data. Participants may be withdrawn from the study early due to adverse events, lack of efficacy, or withdrawal of consent. The trial is not categorized as low intervention, emphasizing its focus on safety and efficacy in a controlled clinical setting.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **MGD019** is the primary experimental medication, formulated as a **concentrate for solution for infusion**. It is an **IgG4 tetravalent bispecific antibody-like protein** targeting PD-1 and CTLA4, developed by MacroGenics Inc. The medication is administered intravenously, with a maximum daily dose of 6 mg/kg and a total maximum dose of 210 mg/kg over a treatment period of 24 weeks. Participant compliance is monitored through regular assessments of infusion administration and dosage adherence.

**Dexamethasone** is used as an auxiliary treatment in the trial. It is available in two forms: a tablet form marketed as Dexamethason 4 mg JENAPHARM® and a non-branded form. The tablet is administered orally, with a maximum daily dose of 24 mg and a total maximum dose of 240 mg over a 30-day period. The chemical origin of dexamethasone is noted, and its administration is monitored to ensure adherence to the prescribed dosing schedule.

Another auxiliary treatment is **Prednisone**, marketed as Prednisona KERN PHARMA 5 mg comprimidos EFG. This medication is also administered orally in tablet form. The maximum daily dose is 10 mg, with a total maximum dose of 2100 mg over a 30-day period. As with other treatments, participant compliance is monitored through regular checks on medication intake and adherence to the dosing regimen.

**Docetaxel** is used both as a comparator and in combination with MGD019. It is provided as a solution for infusion, marketed as Docetaxel AqVida 20 mg/ml. The maximum daily dose is 75 mg/m², with a total maximum dose of 750 mg/m² over a 30-day period. The administration route is intravenous, and compliance is ensured through monitoring of infusion sessions and dosage accuracy.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint of median **radiographic progression-free survival (rPFS)**, as determined by investigator review. This endpoint will provide a measure of the time during which participants with metastatic castration-resistant prostate cancer do not experience disease progression as visualized through radiographic imaging. Secondary endpoints will include a comprehensive set of measures such as objective response rate (ORR) per PCWG3 criteria, duration of response (DoR), time to response (TTR), PSA50 and PSA90 response rates, time to PSA progression, duration of PSA response, overall survival (OS), and time to first symptomatic skeletal event (SSE). Additionally, pain progression and severity will be evaluated using the Brief Pain Index - short form (BPI-sf) questionnaire, alongside functional assessments using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.

Pharmacokinetic parameters of lorigerlimab, such as maximum concentration (Cmax), area under the concentration-time curve (AUC), trough drug concentration (Ctrough or Cmin), clearance (CL), volume of distribution (Vz), and terminal half-life, will also be analyzed. The development of anti-drug antibodies in participants will be monitored to assess immunogenicity. The comparison of adverse events (AEs) between treatment groups will provide additional insights into the safety profile of the investigational treatment. These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to ensure a comprehensive evaluation of the treatment's impact on the disease.