A phase 2, open label study to evaluate safety and clinical activity of balstilimab in monotherapy in patients with advanced/metastatic non-melanoma skin cancers (AGENONMELA).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

18 Jun 2021 → ongoing

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Agencja Badań Medycznych (project ABM nr 2020/ABM/01/00004-00)

External identifiers

EU CT number

2024-517380-22-00

EudraCT number

2020-004622-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Main objective of this study is to confirm the hypothesis that the immune cell activation with balstilimab in monotherapy improves clinical benefit in participants with non-resectable advanced or metastatic nonmelanoma skin cancer such as SCC/BCC, MCC, Kaposi Sarcoma, angiosarcoma and other non-melanoma subtype of skin cancers.

Secondary objectives 4

1. To assess whether balstilimab is effective in the treatment of patients with non-melanoma skin cancers.
2. To further characterize the antitumor activity of balstilimab in patients with non-melanoma skin cancers
3. To evaluate the safety of balstilimab treatment in study group
4. To evaluate the quality of life of balstilimab treatment in study group (To evaluate health status utility scores of patients treated with balstilimab)

Conditions and MedDRA coding

Advanced basal cell carcinoma not amenable to local therapy or after progression on at least one line of systemic therapy Advanced squamous cell carcinoma (basosquamous/metatypicus type) or other skin cancers not amenable to local therapy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. signed written informed consent
2. male or female subjects aged > 18 years
3. histologically proven all types of non-melanoma skin cancers, excluding cutaneous lymphomas
4. patients must have metastatic or locally recurrent disease with measurable or targetable at least one lesion on skin/subcutaneous tissue, which can be measured
5. 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.
6. assess to fresh tumor biopsy
7. ECOG PS of 0-2
8. estimated life expectancy of more than 12 weeks
9. disease must be measurable with at least one unidimensional measurable lesion by RECIST v1.1 (including skin lesions).
10. 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)
11. 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.

Exclusion criteria 17

1. Participation in another interventional treatment at the time of within the past 30 days before C1D1.
2. Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as antiprogrammed death 1 (PD-1), anti-PD-L1 antibody;
3. 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.
4. 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.
5. 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.
6. 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.
7. Prior organ transplantation (including allogeneic stem-cell transplantation).
8. 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.
9. Active or history of any autoimmune disease (except for patients with vitiligo) or immune deficiencies that required treatment with systemic immunosuppressive drugs.
10. 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).
11. Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v5.0; however, sensory neuropathy Grade <= 2 will be acceptable.
12. Pregnancy or lactation.
13. Known alcohol or drug abuse.
14. 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
15. Administration of a life vaccine within 4 weeks prior to study drug administration. Life vaccines are also prohibited during study treatment
16. 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.
17. Legal incapacity or limited legal capacity or any psychiatric condition that would prohibit the understanding or rendering of informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical benefit rate (CBR), defined as a stable disease (SD; partial response (PR) or complete response (CR) as determined by the investigator according to criteria –RECIST 1.1

Secondary endpoints 4

1. Clinical benefit rate (CBR), defined as a stable disease (SD; partial response (PR) or complete response (CR) on two consecutive examinations >= 4 weeks apart, as determined by the investigator according to criteria ir - RECIST
2. Duration of Response (DoR), Progression free/Overall survival rate at 12 and 24 month
3. Incidence of and severity of AEs according to scale NCI CTCAE v 5.0. Changes in vital signs, physical findings, ECG/ECHO parameters, and clinical laboratory results
4. Change from day 1 in patient-reported outcomes (QLQ): : QLQ-C30, EQ-5D-3L, FACT-ICM, In patients +65 year old, Comprehensive Geriatric Assessment (CGA) will be performed at screening (SCR) and end of treatment (EOT)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Sponsor organisation

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Address

Ul. Wilhelma Konrada Roentgena 5

City

Warsaw

Postcode

02-781

Country

Poland

Scientific contact point

Organisation

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Contact name

główny badacz

Public contact point

Organisation

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Contact name

Dział Organizacji Badań Klinicznych NIO-PIB

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications