E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Solid Tumors |
Tumori Solidi Avanzati |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Solid Tumors |
Tumori Solidi Avanzati |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab in subjects with advanced solid tumors. |
Determinare la sicurezza, tollerabilità, tossicità limitante la dose (DLTs), massima dose tollerata (MTD)/dose raccomandata per la Fase 2 di BMS-986178 somministrato da solo o in combinazione con nivolumab e/o ipilimumab in soggetti con tumori solidi avanzati |
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E.2.2 | Secondary objectives of the trial |
To investigate the preliminary anti-tumor activity of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab in subjects with advanced solid tumors; To characterize the pharmacokinetics (PK) of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab; To characterize the immunogenicity of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab and the immunogenicity of nivolumab or ipilimumab administered with BMS- 986178. To assess the proportion of subjects showing a change in pharmacodynamic biomarkers of BMS-986178 administered in combination with nivolumab or nivolumab monotherapy (Part 8). |
Investigare la preliminare attività anti-tumorale di BMS-986178 somministrato in monoterapia o in combinazione con nivolumab e/o ipilimumab in soggeti con tumori solidi avanzati. Caratterizzare la farmacocinetica (PK) di BMS-986178 somministrato in monoterapia o in combinazione con nivolumab e/o ipilimumab. Caratterizzare la immunogenicità di BMS-986178 somministrato in monoterapia o in combinazione con nivolumab e/o ipilimumab, e la immunogenicità di nivolumab o ipilimumab somministrato con BMS-986178 Determinare la proporzione di soggetti che mostrano cambiamenti nella farmacodinamica di biomarcatori di BMS-986178 somminstrato in combinazione con nivolumab o nivolumab in monoterapia (Parte 8) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects must be refractory to or intolerant of established therapy known to provide clinical benefit for their condition, i.e., subjects must not be candidates for regimens known to provide clinical benefit • ECOG (Eastern Cooperative Oncology Group) 0-1 • Men and women 18 years old or older • At least one measurable lesion at baseline by CT (computed tomography) or MRI (magnetic resonance imaging) as per RECIST (Response Evaluation Criteria In Solid Tumors) v1.1 |
• I soggetti devono essere refrattari o intolleranti a terapie stabilite note per provvedere beneficio clinico alla loro condizione, ovvero i soggetti non devono essere candidati a regimi noti per provvedere beneficio clinico • ECOG 0-1 • Soggetti maggiorenni (maschili e femminili) • Almeno una lesione misurabile alla baseline mediante CT (tomografia computerizzata) o MRI (risonanza magnetica) come da RECIST v. 1.1
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E.4 | Principal exclusion criteria |
• Known central nervous system metastases or central nervous system as the only source of disease • Concomitant malignancies • Active known or suspected autoimmune disease • Uncontrolled or significant cardiovascular disease • Major surgery less than 4 weeks before the start of the study |
• Metastasi note al sistema nervoso centrale o sistema nervoso centrale come unica sede di malattia • Neoplasie concomitanti • Nota attiva o sospetta malattia autoimmune • Malattia cardiovascolare non controllata o significativa • Chirurgia importante entro 4 settimane prima dell’inizio dello Studio
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of AE's (adverse events) and SAE's (serious adverse events), AE's leading to discontinuation, deaths and clinical laboratory test abnormalities |
primario Incidenza di Eventi Avversi (AEs) e Eventi Avversi Seri (SAEs), AE che portano a discontinuazione, morte e anormalità in risultati di test di di laboratorio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over 4 years |
Oltre 4 anni |
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E.5.2 | Secondary end point(s) |
• Cmax (maximum observed serum concentration) for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • Tmax (time of maximum observed concentration) for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • AUC(0-t) (area under the concentration-time curve from time zero to the time) for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • AUC(TAU) (area under the concentration-time curve in 1 dosing interval) for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • Ctau (the observed concentration at the end of a dosing interval) for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • CLT (total body clearance) for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • Css-avg [average concentration over a dosing interval (AUC(TAU)/tau)] for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • AI [ratio of an exposure measure at steady state to that after the first dose (exposure measure includes AUC (TAU), Cmax and Ctau)] for BMS- 986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • T-HALFeff [effective elimination half-life to explain degree of accumulation for a specific exposure measure (exposure measure includes AUC(TAU), Cmax and Ctau)] for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • Ctrough [trough observed plasma concentrations (this includes predose concentrations (C0) and Ctau)] for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, if data permits • Immunoassay of anti-nivolumab antibody in combination with anti- BMS-986178 antibody • Immunoassay of anti-ipilimumab antibody in combination with anti- BMS-986178 antibody • Objective Response Rate (ORR) • Progression Free Survival Rate (PFSR) • Immunoassay of anti-BMS-986178 antibody alone |
End point secondario - Cmax (concentrazione di siero massima osservata) per BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - Tmax (tempo di concentrazione massima osservata) per BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - AUC (0-t) (area sotto la curva tempo-concentrazione idal tempo 0 al tempo t) per BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - AUC (TAU) ((area sotto la curva tempo-concentrazione in 1 intervallo di dose) per BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - Ctau (la concentrazione osservata alla fine di un intervallo di dose) BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - CLT (clearance corporea totale) BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - Css-avg [concentrazione media oltre l’intervallo di dose (AUC(TAU)/tau)] BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - AI [rapporto di una misura di esposizione allo stato stazionario rispetto a quella dopo la prima dose (misura di esposizione include AUC (TAU), Cmax e Ctau)] BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - T-HALFeff [emività di eliminazione effettiva per spiegare il grado di accumulazione per una specifica misura di esposizione (misura di esposizione include AUC(TAU), Cmax e Ctau)] BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - Ctrough [concentrazioni osservate mediante plasma (include concentrazioni predose (C0) e Ctau)] BMS-986178 da solo o in combinazione con nivolumab e/o ipilimumab, se i dati lo consentono - Immunoassay di anticorpi anti-nivolumab in combinazione con anticorpi anti-BMS-986178 - immunoassay di anticorpi anti-ipilimumab in combinazione con anticorpi anti-BMS-986178 - Tasso di Risposta Obiettivo (ORR) - Tasso di Sopravvivenza Libera da Malattia (PFSS) - Immunoassay di anticorpi anti-BMS986178 da solo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Cmax; Tmax; AUC(0-t); AUC(TAU); Ctau; CLT; Css-avg; AI; T-HALFeff; Ctrough; Immunoassay of anti-nivolumab antibody in combination with anti-BMS-986178 antibody; Immunoassay of anti-ipilimumab antibody in combination with anti-BMS-986178 antibody : Approximately 100 days after the final study drug administration (end of treatment) • ORR; PFSR: Approximately 2 years • Immunoassay of anti-BMS-986178 antibody alone: Approximately 100 days after 6 months of treatment |
Cmax; Tmax; AUC(0-t); AUC(TAU); Ctau; CLT; Css-avg; AI; T-HALFeff; Ctrough; Immunoassay di anticorpi anti-nivolumab in combinazione con anticorpi anti-BMS-986178; Immunoassay di anticorpi anti-ipilimumab in combinazione con anticorpi anti-BMS-986178: approssimativamente 100 giorni sopo l’ultima somministrazione di farmaco sperimentale (fine del trattamento) • ORR; PFSR: approssimativamente 2 anni • Immunoassay di anticorpi anti-BMS986178 da solo: approssimativamente 100 giorni dopo 6 mesi di trattamento |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity: The secondary objective of immunogenicity will be assessed by the frequency of positive ADA to BMS-986178 or nivolumab or ipilimumab. |
Immunogenicitià: l'obiettivo secondario di immunogenicitià sarà determinato dalla frequeza di ADA positivi a BMS986178 o nivolumab o ipilimumab |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
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 | 4 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | Information not present in EudraCT |
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 |
Canada |
Israel |
United States |
France |
Italy |
Netherlands |
Spain |
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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
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |