Evaluation of Balstilimab Monotherapy in Advanced/Metastatic Non-Melanoma Skin Cancers: A Phase 2 Open-Label Study

Trial ID: 2024-517380-22-00
Protocol: AGENONMELA
Sponsor: Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

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Diseases & Conditions

Skin cancer Basal cell carcinoma

Objectives

The primary objective of this phase 2, open-label study is to confirm the hypothesis that **immune cell activation** with balstilimab in monotherapy improves clinical benefit in participants with non-resectable advanced or metastatic non-melanoma skin cancer, including subtypes such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), Kaposi sarcoma, angiosarcoma, and other non-melanoma skin cancers. This is clinically relevant as it aims to provide a therapeutic option for patients with advanced skin cancers that are not amenable to local therapy or have progressed after systemic treatment.

Secondary objectives include:

Assessing the effectiveness of balstilimab in treating patients with non-melanoma skin cancers.
Further characterizing the antitumor activity of balstilimab in these patients.
Evaluating the safety profile of balstilimab treatment in the study group.
Assessing the quality of life and health status utility scores of patients treated with balstilimab.

These objectives aim to provide comprehensive data on the therapeutic potential and safety of balstilimab, as well as its impact on patients' quality of life.

Participants

The clinical trial involves **participants** diagnosed with advanced basal cell carcinoma or advanced squamous cell carcinoma, as well as other non-melanoma skin cancers that are not amenable to local therapy. The study population includes both **male** and **female** subjects aged 18 years and older. Participants are required to have a histologically proven diagnosis of non-melanoma skin cancers, excluding cutaneous lymphomas, and must present with metastatic or locally recurrent disease with at least one measurable lesion. The trial does not involve a vulnerable population. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and an estimated life expectancy of more than 12 weeks. The sponsor has not provided information regarding the total number of participants. The selection criteria include adequate hematological, hepatic, and renal function, as well as the use of highly effective contraception if there is a risk of conception. Lifestyle considerations such as diet and physical activity are not specified in the available data.

Plans and Procedures

The clinical trial is designed to evaluate the safety and clinical activity of **balstilimab** in monotherapy for patients with advanced or metastatic non-melanoma skin cancers. This is a phase 2, open-label study, which means that both the researchers and participants know which treatment is being administered. The trial aims to confirm the hypothesis that immune cell activation with balstilimab improves clinical benefit in participants with non-resectable advanced or metastatic non-melanoma skin cancer, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), Kaposi sarcoma, angiosarcoma, and other non-melanoma subtypes.

The trial is expected to run from July 1, 2021, to December 31, 2025. Participants will be involved in the study for a maximum treatment period of 24 months. The study includes several key visits: an initial screening visit to determine eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess overall outcomes. The primary endpoint is the clinical benefit rate, defined as stable disease, partial response, or complete response according to RECIST 1.1 criteria. Secondary endpoints include the duration of response, progression-free survival, overall survival rate at 12 and 24 months, and the incidence and severity of adverse events according to NCI CTCAE v5.0.

Participants must meet specific inclusion criteria, such as having histologically proven non-melanoma skin cancers, measurable disease, and an estimated life expectancy of more than 12 weeks. They must also provide signed informed consent and demonstrate adequate hematological and organ function. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The study is conducted with intravenous administration of balstilimab, with a maximum daily dose of 3 mg/kg. The trial is not categorized as low intervention and is not a pediatric formulation.

Treatment

The clinical trial involves the administration of **Balstilimab**, an experimental medication, to evaluate its safety and clinical activity in patients with advanced or metastatic non-melanoma skin cancers. **Balstilimab** is provided as a **solution for infusion** and is administered via the **intravenous route**. The dosage is calculated based on the patient's body weight, with a maximum daily dose of 3 mg/kg. The treatment is scheduled to continue for a maximum period of 24 weeks, with the frequency of administration determined by the study protocol. The active substance in Balstilimab is a protein of other origin, specifically designed to activate immune cells, potentially improving clinical outcomes in the target patient population.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the monotherapy with Balstilimab. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The study aims to confirm the hypothesis that immune cell activation with Balstilimab can provide clinical benefits in patients with non-resectable advanced or metastatic non-melanoma skin cancers, including subtypes such as squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma, Kaposi sarcoma, angiosarcoma, and other non-melanoma skin cancer subtypes.

Efficacy

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the **Clinical Benefit Rate (CBR)**, which is defined as the proportion of patients achieving stable disease (SD), partial response (PR), or complete response (CR) as determined by the investigator according to RECIST 1.1 criteria. Secondary endpoints include the CBR on two consecutive examinations at least four weeks apart, also determined by the investigator according to ir-RECIST criteria. Additional secondary endpoints are the Duration of Response (DoR), progression-free survival, and overall survival rates at 12 and 24 months.

Patient-reported outcomes will be evaluated using validated instruments such as the QLQ-C30, EQ-5D-3L, and FACT-ICM. For patients aged 65 years and older, a Comprehensive Geriatric Assessment (CGA) will be conducted at screening and at the end of treatment. The incidence and severity of adverse events will be assessed according to the NCI CTCAE v5.0 scale, along with changes in vital signs, physical findings, ECG/ECHO parameters, and clinical laboratory results. These assessments will be conducted at specified intervals throughout the study to ensure comprehensive evaluation of the treatment's efficacy and safety.

Inclusion and Exclusion Criteria

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Inclusion Criteria

signed written informed consent
male or female subjects aged > 18 years
histologically proven all types of non-melanoma skin cancers, excluding cutaneous lymphomas
patients must have metastatic or locally recurrent disease with measurable or targetable at least one lesion on skin/subcutaneous tissue, which can be measured
due to progression or tumor extent are disqualified from surgical excision, radiotherapy or other local treatment (systemic naïve population) and/or patient who progressed on systemic treatment.
assess to fresh tumor biopsy
ECOG PS of 0-2
estimated life expectancy of more than 12 weeks
disease must be measurable with at least one unidimensional measurable lesion by RECIST v1.1 (including skin lesions).
adequate hematological and organ function defined by the following parameters: - White blood count (WBC) > 3000/μl - Absolute Neutrophil Count (ANC) > 1500/μl -Hemoglobin (Hb) > 8 g/dl (or > 5.6 mmol/L), may have been transfused to 7 days before C1D1 - Platelet count > 100.000/μl - Adequate hepatic function defined by serum total bilirubin < 2 x ULN, ALT and/or AST < 3 x ULN (or <5xULN with liver metastases) - Adequate renal function defined by serum creatinine < 1.5 x ULN or eGFR > 40 mL/min (as per Cockroft-Gault formula)
Highly effective contraception (that is, methods with a failure rate of less than 1% per year) for both male and female patients if the risk of conception exists.

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Exclusion Criteria

Participation in another interventional treatment at the time of within the past 30 days before C1D1.
Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as antiprogrammed death 1 (PD-1), anti-PD-L1 antibody;
Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [except for palliative bone directed radiotherapy, or radiotherapy administered on non-target superficial lesions], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the study treatment.
Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the subject has not fully recovered from surgery within 4 weeks.
Concurrent systemic therapy with steroids or other immunosuppressive agents (e.g. methotrexate, azathioprine, interferons, mycophenolate, anti-TNF agents and other), or the use of any investigational drug within 28 days before the start of study treatment. Short-term administration of systemic steroids e.g. for allergic reactions or the management of immune-related adverse events [irAE] while on study is allowed. Also, patients requiring hormone replacement with corticosteroids for adrenal insufficiency are eligible if the steroids are administered only for purpose of hormonal replacement and at doses < 10 mg or equivalent prednisone per day. [Note: Patients receiving bisphosphonate or denosumab are eligible.]Conditions requiring systemic anti-arrhythmic therapy known to prolong QT/QTc interval, patients with QTcF interval >480 msec on at least 2 separate and consecutive ECGs at screening or a medical history of long-QT-Syndrome.
Patients with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 1 month in MRI, and do not require continued steroid therapy.
Prior organ transplantation (including allogeneic stem-cell transplantation).
Known history of testing positive HBV or HCV infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening is positive). HIV positive patients are not excluded.
Active or history of any autoimmune disease (except for patients with vitiligo) or immune deficiencies that required treatment with systemic immunosuppressive drugs.
Known severe hypersensitivity reactions to monoclonal antibodies (Grade > 3 NCI-CTCAE v 5.0), history or current evidence of clinically relevant allergies or hypersensitivity, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially uncontrolled asthma).
Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v5.0; however, sensory neuropathy Grade <= 2 will be acceptable.
Pregnancy or lactation.
Known alcohol or drug abuse.
Clinically significant (i.e., active) cardiovascular and/or thromboembolic diseases: a. Cerebral vascular accident or stroke < 6 months prior to enrolment b. Uncontrolled hypertension c. Congestive heart failure (New York Heart Association (NYHA Class III or IV d. Cardiac arrhythmia requiring medication - patient will be included after discussion with Cardiologist. e. Symptomatic ischemic or severe valvular heart disease f. Unstable angina pectoris or a myocardial infarction within 6 months prior to screening, i.e. signing ICF
Administration of a life vaccine within 4 weeks prior to study drug administration. Life vaccines are also prohibited during study treatment
All other significant diseases (for example, inflammatory bowel disease, secondary cancers), which, in the opinion of the Investigator, might impair the patient´s tolerance of the study treatment.
Legal incapacity or limited legal capacity or any psychiatric condition that would prohibit the understanding or rendering of informed consent.