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

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

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.