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SNCTP000003159 | NCT03484923 | BASEC2018-00902

Plattformstudie zur Bewertung der Wirksamkeit und Sicherheit neuen Kombinationstherapien mit Spartalizumab bei Melanomen (CPDR001J2201)

Base de données : BASEC (Importation du 28.03.2024), WHO (Importation du 20.03.2024)
Modifié: 1 févr. 2024 à 01:00
Catégorie de maladie: Mélanome

Brève description de l’étude (Source de données: BASEC)

In dieser klinischen Studie soll geprüft werden, wie gut das Studienmedikament Spartalizumab in Kombination mit LAG525, Capmatinib, Canakinumab oder Ribociclib zur Behandlung von Patienten mit einem fortgeschrittenen Melanom wirkt. Spartalizumab, LAG525, Capmatinib, Canakinumab und Ribociclib sind Medikamente, die von Swissmedic nicht für die Behandlung von Melanomen zugelassen sind. Es werden voraussichtlich maximal 185 Patienten an 25 Studienzentren weltweit an dieser Studie teilnehmen, circa 12 Patienten sind am Universitätsspital Zürich geplant.

Maladies étudiées(Source de données: BASEC)

Melanom (schwarzer Hautkrebs)

Health conditions (Source de données: WHO)

Melanoma

Maladie rare (Source de données: BASEC)

Non

Intervention étudiée (p. ex., médicament, thérapie, campagne) (Source de données: BASEC)

Die Studienteilnehmer erhalten eine der folgenden Studienbehandlungen:
• LAG525 in Kombination mit Spartalizumab
• Capmatinib in Kombination mit Spartalizumab
• Canakinumab in Kombination mit Spartalizumab
• Ribociclib in Kombination mit Spartalizumab
Die Zuteilung der Studienbehandlung erfolgt per Zufall. Sowohl der behandelnde Studienarzt wie auch die Patienten erfahren, welche Studienbehandlung zugeteilt wurde.
Spartalizumab und LAG525 werden alle 4 Wochen per Infusion verabreicht.
Capmatinib und Ribociclib sind Medikamente zum Schlucken.
Canakinumab wird als Injektion alle 4 Wochen verabreicht.
Die Studienbehandlung wird so lange fortgesetzt, wie die Patienten von der Behandlung profitieren, die Krebserkrankung sich nicht verschlechtert und keine inakzeptablen Nebenwirkungen auftreten.
Der Gesundheitszustand der Studienteilnehmer wird regelmässig überwacht und alle 2-3 Monate werden bildgebende Verfahren (CT-Scan / MRI) durchgeführt, um zu beurteilen wie die Krebserkrankung auf die Studienbehandlung anspricht.
Zur Beurteilung der Wirkung der Studienbehandlung werden in dieser Studie auch Biomarker-Analysen durchgeführt. Biomarker sind wichtige biologische «Indikatoren», die im Blut und Tumorgewebe gemessen werden können. Vor Beginn der Studienbehandlung und zu verschiedenen Zeitpunkten während der Behandlung werden Blut- und Tumorgewebeproben (Biopsien) entnommen, damit die Forscher mehr über die Krebserkrankung erfahren und beurteilen können, ob die Studienbehandlung eine Wirkung zeigt.

Interventions (Source de données: WHO)

Drug: PDR001;Drug: LAG525;Drug: INC280;Drug: ACZ885;Drug: LEE011

Critères de participation à l’étude (Source de données: BASEC)

- Alter >= 18 Jahre
- Patienten mit inoperablem oder metastasiertem Melanom
- Patienten, welche bereits eine (oder mehrere) Melanom-Therapie(n) erhalten haben

Critères d’exclusion (Source de données: BASEC)

- Patienten mit Aderhautmelanom oder Schleimhautmelanom
- Patienten mit aktiven oder instabilen Hirnmetastasen
- Schwangere oder Personen die keine ausreichende Verhütung praktizieren

Inclusion/Exclusion Criteria (Source de données: WHO)

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Key inclusion criteria for Arm 1, 2, 3, 4:

- Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma
using AJCC edition 8.

- Previously treated for unresectable or metastatic melanoma:

- Subjects with V600BRAF wild-type disease had to have received prior systemic
therapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1.
Additionally, subjects may have received anti-CTLA-4 as a single agent or in
combination with anti-PD-1/PD-L1, irrespective of the sequence. No additional
systemic treatment was allowed for advanced or metastatic melanoma.

A maximum of two prior lines of systemic therapies for unresectable or metastatic melanoma
were allowed.

The last dose of prior therapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4) had to have been
received more than four weeks before randomization.

- Subjects with V600BRAF mutant disease had to have received prior systemic therapy for
unresectable or metastatic melanoma with anti-PD-1/PD-L1 and V600BRAF inhibitor.
Additionally, subjects may have received anti-CTLA-4 as a single agent or in
combination with anti-PD-1/PD-L1, or MEK inhibitor (in combination with V600BRAF
inhibitor or as a single agent), irrespective of the sequence. No additional systemic
treatment was allowed for advanced or metastatic melanoma.

- A maximum of three prior lines of systemic therapies for unresectable or metastatic
melanoma were allowed.

- The last dose of prior therapy had to have been received more than 4 weeks (for
anti-PD-1, anti-PD-L1, or anti-CTLA-4) or more than 2 weeks (for V600BRAF or MEK
inhibitor) prior to randomization.

- All subjects (with V600BRAF wild-type disease and with V600BRAF mutant disease) had to
have documented disease progression as per RECIST v1.1 while on/after the last therapy
received prior to study entry and while on/after treatment with anti-PD1/PD-L1. The
last progression had to have occurred within 12 weeks prior to randomization in the
study.

- ECOG performance status 0-2.

- At least one measurable lesion per RECIST v1.1.

- At least one lesion, suitable for sequential mandatory tumor biopsies (screening
and on-treatment) in accordance with the biopsy guidelines specified in the
protocol. The same lesion had to be biopsied sequentially.

- Screening tumor biopsy had to fulfill the tissue quality criteria outlined in the
protocol, as assessed by a local pathologist.

Key inclusion criteria for Arm 1A:

- Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma
according to AJCC Edition 8.

- Previously treated for unresectable or metastatic melanoma:

- All subjects had to have received anti-PD-1 checkpoint inhibitor therapy (i.e.,
pembrolizumab or nivolumab) either as monotherapy or in combination with
ipilimumab as the last systemic therapy prior to enrollment and had to have
confirmed disease progression as per RECIST v1.1 (confirmed on a subsequent scan,
which could be the scan performed during screening) while on or after this
therapy prior to enrollment.

- Subjects with V600BRAF wild-type disease had to have received no more than 2
prior systemic therapies, including prior anti-PD-1/PD-L1 (as monotherapy or in
combination with ipilimumab).

- Subjects with V600BRAF mutant disease had to have received no more than 3 prior
systemic therapies, including anti-PD-1/PD-L1 (as monotherapy or in combination
with ipilimumab) and V600BRAF inhibitor (as monotherapy or in combination with a
MEK inhibitor).

- The last dose of anti-PD-1-based therapy had to have been received more than four
weeks prior to the first dose of study treatment.

- The last documented disease progression had to have occurred within 12 weeks
prior to the first dose of study treatment.

- No additional systemic treatment was allowed for advanced or metastatic melanoma
(this included, for example, tumor-infiltrating lymphocyte therapy).

- ECOG performance status 0-1.

- At least one measurable lesion per RECIST v1.1.

- Subjects had to have a baseline tumor sample that was positive for LAG-3 per central
assessment.

Key exclusion criteria common to all combination arms:

- Subjects with uveal or mucosal melanoma.

- Presence of clinically active or unstable brain metastasis at the time of screening.

- Use of any live vaccines against infectious diseases within 3 months before
randomization/enrollment.

- Active infection requiring systemic antibiotic therapy at the time of
randomization/enrollment.

- Subjects with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
days of randomization/enrollment. Inhaled or topical steroids, and adrenal replacement
steroid doses >10 mg daily prednisone equivalent, were permitted in the absence of
active autoimmune disease.

- Active, known or suspected autoimmune disease or a documented history of autoimmune
disease.

- Prior allogenic bone marrow or solid organ transplant.

- History of known hypersensitivity to any of the investigational drugs used in this
study.

- Malignant disease, other than that being treated in this study.

- Prior systemic therapy for unresectable or metastatic melanoma with any
investigational agent or with any other agent except anti-PD-1/PD-L1 and anti-CTLA-4
(and V600BRAF and MEK inhibitors if the subject has V600BRAF mutant disease). Prior
neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months before
the start of the study treatment.

- Medical history or current diagnosis of myocarditis.

- Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening.

Plus de données sur l’étude tirée du registre primaire de l’OMS

https://clinicaltrials.gov/ct2/show/NCT03484923

Plus de données sur l’étude tirée de la base de données de l’OMS (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT03484923
Plus d’informations sur l’étude

Statut de recrutement

Completed

Titre scientifique (Source de données: WHO)

A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma

Type d’étude (Source de données: WHO)

Interventional

Conception de l’étude (Source de données: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Source de données: WHO)

Phase 2

Points finaux primaires (Source de données: WHO)

Overall Response Rate (ORR)

Points finaux secondaires (Source de données: WHO)

Duration of Response (DOR);Overall Survival (OS);Progression Free Survival (PFS);Disease Control Rate (DCR);Percentage of Participants With PDR001 Anti-drug Antibodies (ADA) Positive Result at Baseline;Percentage of Participants With LAG525 Anti-drug Antibodies (ADA) Positive Result at Baseline;Percentage of Participants With ACZ885 Anti-drug Antibodies (ADA) Positive Result at Baseline;Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for PDR001;Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for LAG525;Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for ACZ885;Percentage of Participants With a Favorable Biomarker Profile (pFBP)

Contact pour informations (Source de données: WHO)

Please refer to primary and secondary sponsors

Résultats de l’étude (Source de données: WHO)

Résumé des résultats

pas encore d’informations disponibles

Lien vers les résultats dans le registre primaire

https://clinicaltrials.gov/ct2/show/results/NCT03484923

Informations sur la disponibilité des données individuelles des participants

pas encore d’informations disponibles

Lieux de réalisation des études

Lieux de réalisation des études en Suisse (Source de données: BASEC)

Zurich

Pays où sont réalisées les études (Source de données: WHO)

Australia, Canada, France, Germany, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States

Contact pour plus d’informations sur l’étude

Données sur la personne de contact en Suisse (Source de données: BASEC)

Sandra Ivic
+41797713086
sandra.ivic@novartis.com

Contact pour des informations générales (Source de données: WHO)

Novartis Pharmaceuticals
Novartis Pharmaceuticals

Contact pour des informations scientifiques (Source de données: WHO)

Novartis Pharmaceuticals
Novartis Pharmaceuticals

Autorisation de la commission d’éthique (Source de données: BASEC)

Nom de la commission d’éthique chargée de l’autorisation (dans le cas d’études multicentriques, uniquement la commission directrice)

Kantonale Ethikkommission Zürich

Date d’autorisation de la commission d’éthique

04.10.2018

Plus de numéros d’identification d’étude

Numéro d’identification de l’étude de la commission d’éthique (BASEC-ID) (Source de données: BASEC)

2018-00902

Secondary ID (Source de données: WHO)

2018-000610-38
CPDR001J2201
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