E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced solid tumors and non-Hodgkin lymphoma |
Tumores sólidos avanzados y linfoma no Hodgkin |
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E.1.1.1 | Medical condition in easily understood language |
Advanced solid tumors and non-Hodgkin lymphoma |
Tumores sólidos avanzados y linfoma no Hodgkin |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000020935 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012818 |
E.1.2 | Term | Diffuse large B-cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
- Part 1:To evaluate the efficacy of NIR178 and PDR001 combination in patients with selected advanced solid tumors and diffuse large B cell lymphoma (DLBCL) - Part 2: To assess the efficacy of several intermittent dosing schedules of NIR178 in combination with PDR001 in NSCLC - Part 3: To evaluate efficacy of intermittent dosing schedule of NIR178 in NSCLC and another tumor type |
- Parte 1: Evaluar la eficacia de la combinación de NIR178 y PDR001 en pacientes con tumores sólidos avanzados seleccionados y linfoma difuso de células B grandes (DLBCL). - Parte 2: Evaluar la eficacia de varias posologías de dosis intermitentes de NIR178 en combinación con PDR001 en cáncer de pulmón de células no pequeñas (NSCLC). - Parte 3: Evaluar la eficacia de la posología de dosis intermitente de NIR178 en NSCLC y en otro tipo de tumor. |
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E.2.2 | Secondary objectives of the trial |
- To assess efficacy of NIR178+PDR001 in select advanced solid tumors and lymphoma - To assess the safety and tolerability of the NIR178 and PDR001 combination - To characterize changes in the immune infiltrate in tumors - To characterize the pharmacokinetics (PK) of NIR178, its metabolite NJI765 and PDR001 in combination - To assess immunogenicity of PDR001 |
- Evaluar la eficacia de NIR178 + PDR001 en tumores sólidos avanzados seleccionados y linfoma. - Evaluar la seguridad y la tolerabilidad de la combinación de NIR178 y PDR001. - Caracterizar los cambios en el infiltrado inmunológico en los tumores. - Caracterizar la farmacocinética (PK) de NIR178, de su metabolito NJI765 y de PDR001 en combinación. - Evaluar la inmunogenicidad de PDR001. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically documented advanced or metastatic solid tumors or lymphomas . Part 1: histologically confirmed renal cell carcinoma (RCC), pancreatic cancer, urothelial cancer, head and neck cancer, diffuse large B-cell lymphoma (DLBCL), microsatellite stable (MSS) colon cancer, triple negative breast cancer (TNBC) or melanoma . Part 2: histologically confirmed diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant histology . Part 3: histologically confirmed diagnosis of advanced/metastatic NSCLC and one additional tumor type based on emerging data from part 1 of the study. - Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution’s guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and again during therapy on this study. The collection of recent sample is permitted under the following conditions (both must be met): . Biopsy was collected </= 6 months before 1st dose of study treatment and available at the site. . No immunotherapy was given to the patient since collection of biopsy. - Patients must previously have received at least 1 and no more than 3 prior lines of therapy for their disease - Patients must not have received prior immunotherapy (previous immune checkpoint inhibitors; single agent and/or combination therapy with anti-CTLA-4, anti-PD-1, anti-PD-L1), except for NSCLC patients enrolled in part 3 - Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or as >10 mm with spiral computer tomography (CT) scan, Magnetic Resonance Imaging (MRI), or calipers by clinical exam.
Other protocol defined inclusion criteria may apply. |
- Linfomas o tumores sólidos avanzados o metastásicos histológicamente documentados . Parte 1: carcinoma de células renales (RCC), cáncer pancreático, cáncer urotelial, cáncer de cabeza y cuello, linfoma difuso de células B grandes (DLBCL), cáncer de colon con microsatélites estables (MSS), cáncer de mama triple negativo (TNBC) o melanoma histológicamente confirmado. . Parte 2: Diagnóstico histológicamente confirmado de NSCLC avanzado/metastásico. Los pacientes con histología mixta, deberán presentar una histología predominante. . Parte 3: Diagnóstico histológicamente confirmado de NSCLC avanzado/metastásico y un tipo de tumor adicional en función de los datos que surjan de la parte 1 del estudio. - Los pacientes deberán presentar una zona de enfermedad apta para biopsia y ser candidatos para biopsia de tumor según las pautas del centro que los trate. Los pacientes deberán estar dispuestos a someterse a una nueva biopsia de tumor en la selección y de nuevo durante la terapia en este estudio. Se permite el uso de muestra reciente bajo las siguientes condiciones (deberán cumplirse ambos requisitos): . La biopsia fue recogida </= 6 meses antes de la 1ª dosis del tratamiento del estudio y estar disponible en el centro. . No se le administró inmunoterapia al paciente desde la recogida de la biopsia. - Los pacientes deberán haber recibido previamente por lo menos 1 y no más de 3 líneas previas de terapia para su enfermedad. - Los pacientes no deberán haber recibido inmunoterapia previa (inhibidores del control de la inmunidad (inhibidores checkpoint) previos; monoterapia y/o terapia de combinación con anti-CTLA-4, anti-PD-1, anti-PD-L1), excepto para los pacientes con NSCLC incluidos en la parte 3. - Los pacientes deberán presentar enfermedad medible, definida como por lo menos una lesión que pueda ser medida de forma precisa en al menos una dimensión (deberá registrarse el diámetro más largo para las lesiones no nodulares y el eje más corto para las lesions nodulares) como > 20 mm con técnicas convencionales o como > 10 mm con tomografía computarizada (TC) helicoidal, resonancia magnética (RM) o calibradores con examen clinic.
Pueden aplicar otros criterios de inclusion definidos en el protocolo |
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E.4 | Principal exclusion criteria |
- Ongoing or prior treatment with A2aR inhibitors. Patients previously treated with A2aR inhibitors for non-oncologic indications (e.g. Parkinson’s disease) may be considered for enrollment on a case by case basis. - Current or prior use of immunosuppressive medication within 28 days before the first dose of PDR001, with the exception of intranasal/inhaled corticosteroids or systemic corticosteroids at physiological doses (not exceeding equivalent of 10 mg/day of prednisone) - History of interstitial lung disease or non-infectious pneumonitis - History of another primary malignancy except for: . Malignancy treated with curative intent and with no known active disease >/= 2 years before the first dose of study drug and of low potential risk for recurrence . Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease . Adequately treated carcinoma in situ without evidence of disease - Active or prior documented autoimmune disease within the past 2 years. Patients with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. - More than 3 prior lines of therapy - Participation in another clinical study with an investigational product during the last 21 days prior to starting on treatment.
Other protocol defined exclusion criteria may apply. |
- Tratamiento previo o en curso con inhibidores del A2aR. Los pacientes tratados previamente con inhibidores de A2aR para indicaciones no oncológicas (por ejemplo, enfermedad de Parkinson) pueden ser considerados para inclusión en una base individualizada. - Uso previo o actual de medicación inmunosupresora dentro de los 28 días antes de la primera dosis de PDR001, con la excepción corticosteroides intranasales / inhalados o corticosteroides sistémicos a dosis fisiológicas (no superiores a un equivalente de 10 mg/día de prednisona). - Antecedentes de enfermedad pulmonar intersticial o de neumonitis no infecciosa. - Antecedentes de otra neoplasia maligna primaria excepto: . Neoplasia maligna tratada con fines curativos y sin enfermedad activa conocida >/= 2 años antes de la primera dosis de la medicación del estudio y de bajo riesgo posible de recurrencia. . Cáncer cutáneo no melanoma adecuadamente tratado o lentigo maligno sin evidencia de enfermedad. . Carcinoma in situ adecuadamente tratado sin evidencia de enfermedad. - Enfermedad autoinmune documentada previa o activa dentro de los 2 últimos años. Los pacientes con vitíligo, enfermedad de Grave o psoriasis que no precisen tratamiento sistémico (dentro de los 2 años previos) no serán excluidos. - Más de 3 líneas de terapia. - Participación en otro estudio clínico con un producto de investigación durante los últimos 21 días antes de iniciar el tratamiento. Pueden aplicar otros criterios de exclusion definidos en el protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At protocol define timepoints until End of study. |
En el protocol define momento de evaluación hasta el fin de estudio |
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E.5.2 | Secondary end point(s) |
- DCR (Dose Control Rate), DoR (Duration of Response), PFS (Progression Free Survival), 2 years Overall Survival rate. - Frequency, severity and seriousness of AEs, laboratory abnormalities and other safety parameters. Dose interruptions, reductions and dose intensity. - Change from baseline in TILs - Plasma concentration time profiles of NIR178, NJI765 and PK parameters. Serum concentration time profiles of PDR001 and PK parameters. - Presence and/or concentration of anti-PDR001 antibodies |
-TCE (Tasa de Control de la Enfermedad), DR (duración de la respuesta), SLP (supervivencia libre de progresión), Tasa de supervivencia a los 2 años. - Frecuencia, Severidad y Seriedad del AE, Anormalidades de laboratorio y otros parámetros de seguridad. Interrupciones de dosis, reducciones e intensidad de dosis. - Cambios en los LIT (linfocitos infiltrantes de tumor) respecto a niveles basales. - Perfiles de concentración de plasma respecto al tiempo de NIR178, NJI765 y parámetros de farmacocinética. Perfiles de concentraciones de suero respecto al tiempo de PDR001 y parámetros de farmacocinética. - Presencia y/o concentración de anticuerpos anti-PDR001. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At protocol define timepoints until End of study. |
En el protocol define momento de evaluación hasta el fin de estudio |
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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 | No |
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 | 6 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Singapore |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 when all patients have completed the treatment period and 150-day safety follow-up, and at least 80% of patients have completed at least 24 months of survival follow up from start of study therapy. |
El estudio finalizará cuando todos los pacientes hayan completado el periodo de tratamiento y los 150 dias de seguimiento de seguridad y al menos el 80% de los pacientes hayan completado al menos 24 meses de seguimiento de supervivencia desde el inicio de la terapia del estudio. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |