| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| advanced/refractory solid tumors |
| tumores sólidos avanzados/resistentes |
|
| E.1.1.1 | Medical condition in easily understood language |
| advanced/refractory solid tumors. |
| tumores sólidos avanzados/resistentes |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029514 |
| E.1.2 | Term | Non-small cell lung cancer NOS |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10052362 |
| E.1.2 | Term | Metastatic colorectal cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 24.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10085908 |
| E.1.2 | Term | Cutaneous squamous cell carcinoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10019829 |
| E.1.2 | Term | Hepatocellular carcinoma recurrent |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10076506 |
| E.1.2 | Term | Castration-resistant prostate cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033130 |
| E.1.2 | Term | Ovarian cancer NOS |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To estimate the antitumor efficacy of SOT101 in combination with pembrolizumab |
| Estimar la eficacia antitumoral de SOT101 en combinación con pembrolizumab |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the safety and tolerability of SOT101 in combination with pembrolizumab according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. To further evaluate the antitumor efficacy of SOT101 in combination with pembrolizumab. (Population) pharmacokinetics (PK) of SOT101 in combination with pembrolizumab.To determine the immunogenicity of SOT101 in combination with pembrolizumab |
| Evaluar la seguridad y tolerabilidad de SOT101 en combinación con pembrolizumab según los Criterios terminológicos comunes para acontecimientos adversos (Common Terminology Criteria for Adverse Events, CTCAE), versión 5.0. Evaluar en mayor profundidad la eficacia antitumoral de SOT101 en combinación con pembrolizumab. Farmacocinética (FC) (poblacional) de SOT101 en combinación con pembrolizumab. Determinar la inmunogenicidad de SOT101 en combinación con pembrolizumab. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Be 18 years of age on the day of signing informed consent
2.Ability to understand and sign written informed consent to participate in the study
3.Provides written informed consent for the study
4.Patients with the following histologically or cytologically confirmed solid tumor indications and line of treatment:
•NSCLC
•Colorectal cancer
•cSCC
•Advanced hepatocellular carcinoma
• mCRPC
•Ovarian cancer
5.Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology; lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
mCRPC: Patients with both measurable and non-measurable disease will be enrolled. At least 35 patients with measurable disease will be enrolled. Patients with no measurable disease and only widespread bone disease must have a CTC count of >5 cells per 7.5 mL of blood.
6.Accessible tumor tissue available for fresh biopsy except for mCRPC with no accessible tumor tissue
7.Performance status: Eastern Cooperative Oncology Group (ECOG) performance score 0-1
8.Must have recovered from all AEs (except alopecia) due to previous therapies to grade ≤1 toxicity (excluding alopecia) or have stable grade 2 neuropathy
Have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of study interventions.
9.Hematology:
9.1. Absolute neutrophil count ≥1500/µL
9.2. Platelets ≥100 000/µL
9.3. Hemoglobin ≥9.0 g/dL (criteria must be met without packed red blood cell transfusion within the prior 2 weeks; patients can be on a stable dose of erythropoietin [≥ 3 months])
10.Renal function: Creatinine clearance as measured by glomerular filtration rate ≥30 mL/min using Cockcroft-Gault equation
11.Hepatic function: Alanine transaminase (ALT)/aspartate transaminase (AST) ≤2.5× upper limit of normal (ULN) and total bilirubin ≤1.5×ULN or direct bilirubin ≤ ULN in patients without liver metastasis (benign hereditary hyperbilirubinemias). In patients with liver metastasis, ALT/AST ≤5×ULN is allowed but total bilirubin must be ≤2×ULN.
12.Prothrombin time and activated partial thromboplastin time ≤1.5×ULN
13.Patients who are hepatitis B (HBV) surface antigen positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load before study entry (ICF signature).
14.Patients with history of hepatitis C (HCV) infection are eligible if HCV viral load is undetectable at screening. Patients must have completed anti-viral therapy at least 4 weeks before study entry (ICF signature).
15.A female patient is eligible to participate if she is not pregnant, not breastfeeding, and one of the following conditions applies:
15.1.Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for
12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle stimulating hormone measurement is insufficient.
15.2.A WOCBP who agrees to use a highly effective contraceptive method during the treatment period and for at least 120 days after the last dose of pembrolizumab or at least 30 days after the last dose of SOT101, whichever is later.
• WOCBP can only be included after a negative serum pregnancy test at screening.
• Highly effective contraception includes:
o Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation:
Oral
Intravaginal
Transdermal
o Progestogen-only hormonal contraception associated with inhibition of ovulation:
Oral
Injectable
Implantable
oIntrauterine device
oIntrauterine hormone-releasing system
oBilateral tubal occlusion
oVasectomized partner provided the partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success.
oSexual abstinence defined as refraining from heterosexual intercourse during the entire treatment period and for at least 120 days after the last dose of pembrolizumab or at least 30 days after the last dose of SOT101, whichever is later. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.
16. Male patients must agree to use a condom during the treatment period and for at least 120 days after the last dose of pembrolizumab or at least 30 days after the last dose of SOT101, whichever is later. |
1.Tener 18 años de edad el día de la firma del consentimiento informado.2.Capacidad de entender y firmar un consentimiento informado por escrito para participar en el estudio.3.Proporcionar el consentimiento informado por escrito para el estudio.4.Pacientes con las siguientes indicaciones de tumores sólidos confirmados histológica o citológicamente y línea de tratamiento:
•CPNM, •Cáncer colorrectal, •CEC, •Carcinoma hepatocelular avanzado, •Cáncer ovárico. 5.Presentar enfermedad medible en base a los criterios RECIST 1.1 según la evaluación del investigador/de radiología del centro local; las lesiones situadas en un área previamente irradiada se consideran medibles si se ha demostrado progresión en dichas lesiones.CPRCm: Se inscribirá a pacientes con enfermedad medible y no medible. Se inscribirá al menos a 35 pacientes con enfermedad medible. Los pacientes sin enfermedad medible y que solo presenten enfermedad ósea diseminada deben tener un recuento de CTC de >5 células por 7,5 ml de sangre.6.Tejido tumoral accesible disponible para biopsia reciente, excepto para el CPRCm sin tejido tumoral accesible. 7.Estado funcional: estado funcional de 0-1 del Grupo Cooperativo Oncológico del Este (Eastern Cooperative Oncology Group, ECOG). 8.Debe haberse recuperado de todos los AA (excepto la alopecia) debidos a tratamientos anteriores hasta una toxicidad de grado ≤1 (excepto la alopecia) o presentar neuropatía estable de grado 2. Tener una función orgánica adecuada tal y como se define a continuación. Las muestras deben recogerse en los 10 días previos al inicio de las intervenciones del estudio.
9.Hematología:9.1.Recuento absoluto de neutrófilos ≥1500/µl. 9.2. Plaquetas ≥100 000/μl
9.3.Hemoglobina ≥9,0 g/dl (deben cumplirse los criterios sin transfusión de concentrado de eritrocitos en las 2 semanas anteriores; los pacientes pueden estar recibiendo una dosis estable de eritropoyetina [≥3 meses]).10. Función renal: Aclaramiento de creatinina según lo medido por una tasa de filtración glomerular ≥30 ml/min utilizando la ecuación de Cockcroft-Gault
11.Función hepática: ALT/AST ≤2,5 × límite superior de la normalidad (LSN) y bilirrubina total ≤1,5 × LSN o bilirrubina directa ≤LSN en pacientes sin metástasis hepática (se permiten hiperbilirrubinemias hereditarias benignas, p. ej., síndrome de Gilbert, si la bilirrubina total es ≤3 mg/dl). En pacientes con metástasis hepática, se permite ALT/AST ≤5 × LSN, pero la bilirrubina total debe ser ≤2 × LSN.12.Tiempo de protrombina y tiempo de tromboplastina parcial activada ≤1,5 × LSN.13.Los pacientes positivos para el antígeno de superficie de VHB son aptos si han recibido tratamiento antiviral contra el VHB durante al menos 4 semanas y tienen una carga viral del VHB indetectable antes de entrar en el estudio (firma del FCI). Los pacientes deben seguir recibiendo tratamiento antiviral a lo largo de todo el tratamiento del estudio y seguir las directrices locales para el tratamiento antiviral contra el VHB tras la finalización de las intervenciones del estudio. Las pruebas de selección del VHB no son necesarias a menos que haya antecedentes conocidos de infección por el VHB.14.Los pacientes con antecedentes de infección VHC son aptos si la carga viral del VHC es indetectable en la selección. Los pacientes deben haber completado el tratamiento antiviral al menos 4 semanas antes de la entrada en el estudio (firma del FCI). Las pruebas de selección del VHC no son necesarias a menos que haya antecedentes conocidos de infección por el VHC.15.Mujer que no esté embarazada ni en período de lactancia y que cumpla una de las siguientes condiciones:15.1.No ser una mujer con capacidad de concebir -MCC, es decir mujer fértil, que ha pasado la menarquia y no es posmenopáusica, salvo que se haya sometido a una esterilización permanente como histerectomía, salpingectomía bilateral y ooforectomía bilateral. La situación de posmenopausia se define como la ausencia de menstruación durante 12 meses sin una causa médica alternativa. Concentración alta de hormona foliculoestimulante en el intervalo posmenopáusico se puede utilizar para confirmar la situación de posmenopausia en las mujeres que no utilizan anticonceptivos hormonales ni tratamiento de reposición hormonal. En ausencia de 12 meses de amenorrea, una única medición de la hormona foliculoestimulante es insuficiente.15.2.MCC que acepte utilizar un método anticonceptivo muy eficaz durante el período de tratamiento y durante un mínimo de 120 días tras la última dosis de pembrolizumab o un mínimo de 30 días tras la última dosis de SOT101, lo que ocurra más tarde.Las MCC solo pueden ser incluidas en el estudio si resultado negativo de prueba de embarazo en suero en la selección.16.Los pacientes varones deben aceptar utilizar un preservativo durante el período de tratamiento y durante un mínimo de 120 días tras la última dosis de pembrolizumab o un mínimo de 30 días tras la última dosis de SOT101. |
|
| E.4 | Principal exclusion criteria |
1.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a grade ≥3 AE
2.Prior exposure to drugs that are agonists of IL-2 or IL-15
3.Prior systemic anti-cancer therapies, including investigational agents, before study entry (ICF signature):
3.1. Less than 4 weeks for systemic chemotherapy and immuno-oncology therapies; and for tyrosine kinase inhibitors 4 weeks or 5 half-lives (whichever is shorter)
3.2. Less than 4 weeks from major surgeries and not recovered adequately from the procedure and/or any complications from the surgery
4.Has received prior radiotherapy within 2 weeks of the start of study interventions. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system disease.
5.NSCLC indication only: Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study interventions
6.Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study interventions
Prior/concurrent clinical study experience
7.Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks or 5 half lives (whichever shorter) before study entry (ICF signature). Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks or 5 half lives (whichever shorter) after the last dose of the previous investigational agent.
8.Clinically significant cardiac abnormalities including prior history of any of the following:
8.1. Cardiomyopathy, with left ventricular ejection fraction ≤50% at screening
8.2. Congestive heart failure of New York Heart Association grade ≥2
8.3. History of clinically significant, atherosclerotic cardiovascular disease, specifically myocardial infarction, unstable angina, cerebrovascular accident within 6 months prior to the first dose of study interventions, and any history of coronary heart disease and clinically significant peripheral and/or carotid artery disease
8.4.Prolongation of QTcF >450 msec
8.5.Clinically significant cardiac arrythmia that cannot be controlled with adequate medication
9.Uncontrolled hypertension defined as systolic blood pressure >160 mmHg, diastolic blood pressure >110 mmHg. Patients with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry (ICF signature).
10. Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years.
11.Has had an allogeneic tissue/solid organ transplant
12.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study interventions
13.History of or serology positive for HIV
14.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Patients with basal cell carcinoma of the skin or carcinoma in situ that have undergone potentially curative therapy are not excluded.
15.Has known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, and without requirement of steroid treatment for at least 14 days prior to the first dose of study interventions.
16.Has severe hypersensitivity (grade ≥3) to pembrolizumab and/or any of its excipients
17.Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
18. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
19.Has an active infection requiring systemic therapy
20.Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
21.Has a known psychiatric or substance abuse disorder that would interfere with the patient’s ability to cooperate with the requirements of the study |
| 1.Haber recibido tratamiento previo con un fármaco anti-PD-1, anti-PD-L1 o anti-PD-L2, o con un fármaco dirigido a otro receptor de linfocitos T estimulador o coinhibidor (p. ej., antígeno 4 de linfocitos T citotóxicos, CD134 [OX40], CD137) y haber interrumpido dicho tratamiento debido a un AA de grado ≥3. 2.Exposición previa a fármacos que sean agonistas de IL-2 o IL-15. 3.Tratamientos antineoplásicos sistémicos previos, incluidos los fármacos en investigación, antes de la entrada en el estudio (firma del FCI): ver Protocolo.4.Haber recibido radioterapia previa dentro de las 2 semanas anteriores al inicio de las intervenciones del estudio. Los pacientes deben haberse recuperado de todas las toxicidades relacionadas con la radiación, no requerir corticoesteroides y no haber tenido neumonitis por radiación. Se permite un periodo de reposo farmacológico de 1 semana para la radiación paliativa (≤2 semanas de radioterapia) en la enfermedad del sistema nervioso central.5.Solo indicación de CPNM: Haber recibido radioterapia en el pulmón de >30 Gy en los 6 meses anteriores a la primera dosis de las intervenciones del estudio.6.Haber recibido una vacuna viva o viva atenuada en los 30 días previos a la primera dosis de las intervenciones del estudio.7.Estar participando actualmente o haber participado en un estudio de un fármaco en investigación o haber utilizado un dispositivo en investigación en las 4 semanas o 5 semividas (lo que sea más corto) anteriores a la entrada en el estudio (firma del FCI). Los pacientes que hayan entrado en la fase de seguimiento de un estudio de investigación pueden participar siempre que hayan transcurrido 4 semanas o 5 semividas (lo que sea más corto) después de la última dosis del fármaco en investigación anterior.8.Anomalías cardíacas clínicamente significativas, incluidos antecedentes de cualquiera de las siguientes afecciones: ver Protocolo.9.Hipertensión no controlada, definida como tensión arterial sistólica >160 mm Hg o tensión arterial diastólica >110 mm Hg. Los pacientes con hipertensión no controlada deben recibir tratamiento médico con una pauta estable para controlar la hipertensión antes de la entrada en el estudio (firma del FCI).10.Haberse sometido a un alotrasplante previo de células madre hematopoyéticas en los últimos 5 años. (Los pacientes que se hayan sometido a un trasplante hace más de 5 años son aptos siempre que no haya síntomas de enfermedad injerto contra huésped).11.Haber recibido un alotrasplante de tejidos/órganos sólidos.12.Presentar un diagnóstico de inmunodeficiencia o estar recibiendo tratamiento crónico con corticoesteroides sistémicos (en dosis que exceden los 10 mg diarios de equivalente de prednisona) o cualquier otra forma de tratamiento inmunodepresor en los 7 días previos a la primera dosis de las intervenciones del estudio.13.VIH.14.Tener otra neoplasia maligna conocida que esté progresando o ha requerido tratamiento activo en los últimos 5 años. Los pacientes con carcinoma basocelular cutáneo o carcinoma in situ (p. ej., carcinoma de mama, cáncer de cuello uterino in situ) que se hayan sometido a un tratamiento potencialmente curativo no quedan excluidos.15.Metástasis activas del sistema nervioso central o meningitis carcinomatosa. Los pacientes con metástasis cerebrales previamente tratadas pueden participar siempre que sean estables desde el punto de vista radiológico, es decir, sin signos de progresión durante al menos 4 semanas mediante la repetición de exploraciones por la imagen (obsérvese que la repetición de las exploraciones por la imagen debe realizarse durante la selección del estudio), clínicamente estables y sin necesidad de tratamiento con corticoesteroides durante al menos 14 días antes de la primera dosis de las intervenciones del estudio.16. Hipersensibilidad grave (grado ≥3) conocida a pembrolizumab o a cualquiera de sus excipientes.17.Enfermedad autoinmunitaria activa que ha requerido tratamiento sistémico en los últimos 2 años (es decir, el uso de agentes modificadores de la enfermedad, corticosteroides o fármacos inmunosupresores). El tratamiento de sustitución (p. ej., tiroxina, insulina, corticoesteroides en dosis fisiológicas para la insuficiencia suprarrenal o hipofisaria) no se considera una forma de tratamiento sistémico y está permitido.18.Antecedentes de neumonitis/enfermedad pulmonar intersticial (no infecciosa) que requiriera corticoesteroides o tener neumonitis/enfermedad pulmonar intersticial actual. 19.Infección activa que requiera tratamiento sistémico.20.Cualquier afección, tratamiento o anomalía analítica que pueda confundir los resultados del estudio, interferir en la participación del paciente durante todo el estudio o que para el paciente no sea lo mejor participar, en opinión del investigador responsable del tratamiento.21.Padecer un trastorno psiquiátrico o de abuso de sustancias conocido que pudiera interferir en la capacidad del paciente para cooperar con los requisitos del estudio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) in patients with measurable disease |
| • Ratio de respuesta objetiva según RECIST 1.1 (MRG) e iRECIST (MRGi) en pacientes con enfermedad medible |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Type, frequency, and severity of treatment-emergent adverse events (TEAEs); adverse events of special interest (AESIs); safety laboratory findings; vital signs; electrocardiography (ECG) findings; • ORR according to RECIST for immune-based therapeutics (iRECIST) (iORR) in patients with measurable disease
• Best overall response according to RECIST 1.1 (BOR) and iRECIST (iBOR) in patients with measurable disease
• Duration of response according to RECIST 1.1 (DoR), iRECIST (iDoR), and Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified RECIST 1.1 (metastatic castration-resistant prostate cancer [mCRPC] only)
• Clinical benefit rate according to RECIST 1.1 (CBR), iRECIST (iCBR), and PCWG3-modified RECIST 1.1 (mCRPC only)
• Progression-free survival (PFS) according to RECIST 1.1, iRECIST (iPFS), and PCWG3-modified RECIST 1.1 (mCRPC only)
• Time to response according to RECIST 1.1 (TtR) and iRECIST (iTtR) in patients with measurable disease
• mCRPC only:
o Circulating tumor cell (CTC) count conversion from >5 to <5 cells per 7.5 mL of blood
o Confirmed prostate-specific antigen (PSA) decline of ≥50%
o Time to confirmed PSA progression
• Plasma concentrations of SOT101 over time;
• Incidence, titer, and time course of anti-drug antibodies (ADAs) against SOT101 |
• Tipo, frecuencia e intensidad de los acontecimientos adversos surgidos durante el tratamiento (AAST); acontecimientos adversos de• Tipo, frecuencia e intensidad de los acontecimientos adversos surgidos durante el tratamiento (AAST); acontecimientos adversos de especial interés (AAEI); resultados analíticos de seguridad; constantes vitales; hallazgos del electrocardiograma (ECG)
• TRO según RECIST para tratamientos inmunitarios (iRECIST) (TROi) en pacientes con enfermedad medible
• Mejor respuesta global según RECIST 1.1 (MRG) e iRECIST (MRGi) en pacientes con enfermedad medible
• Duración de la respuesta según RECIST 1.1 (DdR), iRECIST (DdRi) y RECIST 1.1 modificados por el Grupo de Trabajo de Ensayos Clínicos de Cáncer de Próstata 3 (Prostate Cancer Clinical Trials Working Group 3, PCWG3) (solo cáncer de próstata resistente a la castración metastásico [CPRCm])
• Tasa de beneficio clínico según RECIST 1.1 (TBC), iRECIST (TBCi) y RECIST 1.1 modificados por PCWG3 (solo CPRCm)
• Supervivencia sin progresión (SSP) según RECIST 1.1, iRECIST (SSPi) y RECIST 1.1 modificados por PCWG3 (solo CPRCm)
• Tiempo hasta la respuesta según RECIST 1.1 (THR) e iRECIST (THRi) en pacientes con enfermedad medible
• Solo CPRCm:
o Conversión del recuento de células tumorales circulantes (CTC) de >5 a <5 células por 7,5 ml de sangre
o Descenso confirmado del antígeno prostático específico (prostate-specific antigen, PSA) de ≥50 %.
o Tiempo transcurrido hasta la progresión confirmada del PSA
• Concentraciones plasmáticas de SOT101 a lo largo del tiempo
• Incidencia, título y evolución temporal de los anticuerpos antifármaco (AAF) contra SOT101 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Georgia |
| United States |
| Belgium |
| Czechia |
| France |
| Germany |
| Italy |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The study will end one year after the last patient’s last dose of SOT101 and/or pembrolizumab (whichever occurs later). A patient is considered to have completed the study if s/he has completed all phases of the study including the last follow-up contact |
| El estudio finalizará un año después de la última dosis del último paciente de SOT101 y/o pembrolizumab (lo que ocurra más tarde). Se considera que un paciente ha completado el estudio si ha completado todas las fases del estudio, incluido el último contacto de seguimiento. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 12 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 12 |
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