| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Synovial sarcoma |
| Sarcoma sinoviale |
|
| E.1.1.1 | Medical condition in easily understood language |
| Synovial sarcoma |
| Sarcoma sinoviale |
|
| 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 | PT |
| E.1.2 | Classification code | 10042863 |
| E.1.2 | Term | Synovial sarcoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of NY-ESO-1-Specific (c259) T Cells, alone or in combination with other anti-cancer agents, in HLA-A*02:01, HLAA* 02:05 and/or HLA-A*02:06 participants with NY-ESO-1- and/or LAGE-1a positive solid tumors |
| Valutare l’efficacia di cellule T NY-ESO-1-specifiche (c259), in monoterapia o in associazione con altri agenti antitumorali, in pazienti HLA-A*02:01, HLA-A*02:05 e/o HLA-A*02:06 con tumori solidi NY-ESO-1- e/o LAGE-1a positivi |
|
| E.2.2 | Secondary objectives of the trial |
- To further evaluate the efficacy of NY-ESO-1 Specific (c259) T Cells alone or in combination with other anti-cancer agents in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 participants with NY-ESO-1 and/or LAGE-1a positive solid tumors
- To evaluate the safety and tolerability of NYESO- 1 Specific (c259) T Cells alone or in combination with other anti-cancer agents in HLA-A*02:01, HLA-A*02:05 and/or HLAA* 02:06 participants with NY-ESO-1- and/or LAGE-1a positive solid tumors |
- Valutare ulteriormente l’efficacia di cellule T NY-ESO-1-specifiche (c259), in monoterapia o in associazione con altri agenti antitumorali, in pazienti HLA-A*02:01, HLA-A*02:05 e/o HLA-A*02:06 con tumori solidi NY-ESO-1- e/o LAGE-1a positivi
- Valutare sicurezza e tollerabilità di cellule T NY-ESO-1-specifiche (c259), in monoterapia o in associazione con altri agenti antitumorali, in pazienti HLA-A*02:01, HLA-A*02:05 e/o HLA-A*02:06 con tumori solidi NY-ESO-1- e/o LAGE-1a positivi |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies
Specify title, date and version of each substudy with relative objectives: SUBSTUDY 1: GSK3377794 IN PREVIOUSLY UNTREATED ADVANCED METASTATIC OR UNRESECTABLE SYNOVIAL SARCOMA
SUBSTUDY 2: PREVIOUSLY TREATED ADVANCED METASTATIC OR UNRESECTABLE NY-ESO-1-POSITIVE SYNOVIAL SARCOMA
|
Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sottostudio 1: Valutazione della sicurezza e dell’attività antitumorale di GSK3377794 in pazienti HLA-A2+ affetti da sarcoma sinoviale NY-ESO-1 positivo avanzato metastatico o non resecabile non precedentemente trattato
Sottostudio 2: Valutazione della sicurezza e dell’attività antitumorale di GSK3377794 in pazienti HLA-A2+ affetti da sarcoma sinoviale NY-ESO-1 positivo avanzato metastatico o non resecabile precedentemente trattato
|
|
| E.3 | Principal inclusion criteria |
- Subject must be >=10 years of age at the time of signing the informed consent.
- Participant enrolled under clinical drug product supply must also weigh =40 kg.
- Subject has a diagnosis of synovial sarcoma confirmed by histology.
- Subject has advanced (metastatic or unrespectable) synovial sarcoma.
- In substudy 1, subject with metastatic synovial sarcoma who is newly diagnosed or previously untreated
- In substudy 2, at the time of treatment, subject has received/completed treatment with anthracycline or anthracycline with ifosfamide for advanced (metastatic or inoperable) disease and progressed.
- Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.
- An archival sample from most recent biopsy or fresh biopsy (if collected as part of standard of care) of tumor tissue should be available to perform NY-ESO-1 antigen expression analysis
- All the Inclusion Criteria in 1-7 must apply again prior to leukapheresis.
- Subject must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated test in a designated central laboratory.
- Subjects tumor has been pathologically reviewed by a designated central laboratory with confirmed positive NY-ESO-1 expression
- Performance status: Eastern Cooperative Oncology Group of 0-1.
- Participant must have adequate organ function and blood cell counts, 7 days prior to procedure, as indicated by the following laboratory values in Table 4 in the protocol.
- Subject must have adequate organ function and blood cell counts 7 days prior to leukapheresis.
- Female subjects of childbearing potential must have a negative urine or serum pregnancy test.
- Subject has measurable disease according to RECIST v1.1.
- Supportive radiotherapy has not affected >25% of bone marrow.
-A biopsy (excisional, incisional, or core) of non-target tumor tissue obtained within 28 days prior to initiating lymphodepleting chemotherapy is mandatory. If it is not feasible to obtain a fresh biopsy, an archival tumor tissue (FFPE block) taken after completion of the participant's last line of therapy, preferably within 90 days prior to initiating lymphodepleting chemotherapy, may be accepted at the
discretion of the Medical Monitor (or designee). This biopsy will be used as baseline for biomarker analyses.
For a detailed list of Inclusion Criteria's please refer to the protocol |
- I pazienti devono avere un’età pari o superiore a 10 anni al momento della firma del consenso informato e un peso corporeo >= 40 kg
- Diagnosi di sarcoma sinoviale confermata da istologia
- Paziente affetto da sarcoma sinoviale avanzato (metastatico o non resecabile).
- Sottostudio 1: paziente con sarcoma sinoviale metastatico o non resecabile che sia di nuova diagnosi o precedentemente non trattato
- Sottostudio 2: paziente attualmente in trattamento o che ha completato il trattamento con almeno una terapia standard che abbia compreso antraciclina o antraciclina con ifosfamide per malattia avanzata (metastatica o inoperabile).
- Soggetti di sesso maschile o femminile. Al momento della leucaferesi e del trattamento è richiesta l’aderenza ai requisiti di contraccezione
- Positività del paziente agli alleli HLA-A*02:01, HLA-A*02:05 e/o HLA-A*02:06 valutata tramite test validato eseguito presso un laboratorio centralizzato dello studio.
- Revisione del tumore del partecipante da parte di un laboratorio centralizzato con positività confermata all’espressione di NY-ESO-1
- Performance status: 0-1 secondo l’Eastern Cooperative Oncology Group (ECOG)
- Il paziente deve presentare un’adeguata funzionalità d’organo e valori ematici adeguati 7 giorni prima della leucaferesi
- Pazienti di sesso femminile potenzialmente fertili (FCBP, Female participants of childbearing potential) devono avere un test di gravidanza sulle urine o sul siero negativo
- Il paziente deve avere malattia misurabile in base a RECIST v. 1.1.
- La radioterapia di supporto non deve aver interessato una porzione >25% del midollo osseo.
Fare riferimento al protocollo per la lista dettagliata dei criteri di inclusione. |
|
| E.4 | Principal exclusion criteria |
- In substudy 1, subject has been previously treated for metastatic synovial sarcoma.
Central nervous system metastases.
- Any other prior malignancy that is not in complete remission.
- Previous treatment with genetically engineered NY-ESO-1-specific T cells.
- Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
- Prior gene therapy using an integrating vector.
- Previous allogeneic hematopoietic stem cell transplant.
- Clinically significant systemic illness: serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the subject’s ability to tolerate protocol therapy or significantly increase the risk of complications, or, prior or active demyelinating disease.
- Participants are not eligible for leukapharesis if any of the Exclusion criteria 1-8 apply.
Please note in particular that mandatory washout period restrictions must be respected (Table 5) before starting leukapheresis. In addition, participants are not eligible for leukapharesis if any of the following criteria apply.
- Subject has history of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
- Uncontrolled intercurrent illness
- Current active liver or biliary disease.
- Pregnant or breastfeeding females (due to risk to fetus or newborn).
- Prior/concomitant therapy: any prior treatment-related toxicities must be Common terminology criteria for adverse events <=Grade 1 at the time of initiating study intervention (except for non-clinically significant toxicities).
- Other standard of care lines of therapy are allowed only if guidelines and washout periods are followed.
- Subject has active infection as defined in the protocol
- Subject has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
- Subject had major surgery <=28 days of first dose of study intervention.
- Participant has received live vaccine within 4 weeks prior to lymphodepletion or intends to receive live vaccine during the 3 month period following administration of GSK3377794.
For a detailed list of Exclusion Criteria's please refer to the Protocol |
- Nel Sottostudio 1, paziente precedentemente trattato per sarcoma sinoviale metastatico.
- Metastasi al sistema nervoso centrale (SNC).
- Qualsiasi altro tumore maligno non in remissione completa.
- Precedente trattamento con cellule T NY-ESO-1-specifiche geneticamente modificate.
- Precedente vaccino a base di NY-ESO-1 o anticorpi mirati a NY-ESO-1.
- Precedente terapia genica con vettore integrante.
- Precedente trapianto di cellule staminali emopoietiche allogeniche.
- Malattia sistemica clinicamente significativa: gravi infezioni attive o significativa disfunzione cardiaca, polmonare, epatica o di altro organo che a giudizio dello sperimentatore comprometterebbe la capacità del paziente di tollerare la terapia prevista dal protocollo o aumenterebbe in modo significativo il rischio di complicanze.oppure: patologia demielinizzante pregressa o in corso.
- Soggetto con anamnesi di grave malattia autoimmune o immuno-mediata cronica o ricorrente (nei 12 mesi precedenti la leucaferesi) che abbia richiesto la somministrazione di steroidi o altri trattamenti immunosoppressivi.
- Patologia incontrollata intercorrente
- Malattie del fegato o delle vie biliari in corso
- Soggetti di sesso femminile in gravidanza o allattamento (per via del rischio nei confronti del feto o del neonato).
- Terapia precedente/concomitante:
- qualsiasi tossicità correlata a un trattamento precedente deve essere di grado CTCAE (Versione 5.0) =1 al momento di iniziare l’intervento in studio (con l’eccezione di tossicità non clinicamente
significative)
- altre linee di terapia standard sono consentite solo se sono rispettate le linee guida e i periodi di washout
- Paziente con infezione attiva come definita nel protocollo
- Disturbi psichiatrici o da abuso di sostanze noti che potrebbero interferire con l’aderenza ai requisiti dello studio.
- Paziente sottoposto a intervento di chirurgia maggiore <=28 giorni prima della prima dose di intervento in studio.
- Partecipante che abbia ricevuto un vaccino vivo nelle 4 settimane precedenti la chemioterapia di linfodeplezione
Fare riferimento al protocollo per la lista dettagliata dei criteri di esclusione. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall Response Rate (ORR) per RECIST v1.1 |
| Tasso di risposta globale (ORR) in base a RECIST v1.11 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Up to 5 Years |
| Fino a 5 anni |
|
| E.5.2 | Secondary end point(s) |
To further evaluate the efficacy of NY-ESO-1
- Time to Response (TTR)
- Duration of Response (DoR)
- Disease Control Rate (DCR)
- Progression Free Survival (PFS)
- Overall Survival (OS)
To evaluate the safety and tolerability of NYESO-1
- Adverse events (AEs) including serious adverse events (SAEs)
- Incidence, severity and duration of the AEs of special interest (AESI; as defined in protocol)
- Laboratory parameters Replication Competent Lentivirus (RCL)
- T cell Persistence: Maximum transgene expansion (Cmax), time to Cmax (Tmax), and persistence (area under the time curve from zero to time t
AUC(0-t)), as data permit
- Instances of Insertional oncogenesis (IO) |
Valutare ulteriormente l’efficacia di cellule T NY-ESO-1-specifiche
• Tempo alla risposta (TTR)
• Durata della risposta (DoR)
• Tasso di controllo della malattia (Disease Control Rate_DCR)
• Sopravvivenza libera da progressione (PFS)
• Sopravvivenza complessiva (Overall Survival_OS)
Valutare sicurezza e tollerabilità di cellule T NY-ESO-1-specifiche
• Eventi avversi (AE) compresi eventi avversi serii (SAE)
• Incidenza, gravità e durata degli AE di particolare interesse (AESI; come da protocollo)
• Parametri di laboratorio
• Lentivirus competente per la replicazione (RCL)
• Persistenza linfociti T: Massima espansione transgenica (Cmax), tempo a Cmax (Tmax) e persistenza (area sottesa alla curva da zero al tempo t AUC(0-t)), se i dati lo consentono
• Casi di oncogenesi inserzionale (IO) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Up to 5 Years |
| Fino a 5 anni |
|
| 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 | No |
| 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 | No |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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 | 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 |
| United States |
| France |
| Germany |
| Italy |
| Netherlands |
| 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
|
|
| 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 | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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