Eligibility Details:
Key inclusion criteria:
- 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 must 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 is allowed for advanced
or metastatic melanoma.
A maximum of two prior lines of systemic therapies for unresectable or metastatic melanoma
are allowed.
The last dose of prior therapy (anti-PD-1, anti-PD-L1 or anti-CTLA-4) must have been
received more than four weeks before randomization.
- Subjects with V600BRAF mutant disease must 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 is allowed for advanced or metastatic melanoma .
A maximum of three prior lines of systemic therapies for unresectable or metastatic
melanoma are allowed.
The last dose of prior therapy must 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) must
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 must have occured 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 protocol. The same
lesion must be biopsied sequentially.
- Screening tumor biopsy must fulfill the tissue quality criteria outlined in the
protocol, as assessed by a local pathologist
Key exclusion criteria common to all combination arms:
- Subjects with uveal or mucosal melanoma
- Presence of clinically active or unstable brain metastasis at time of screening. Note:
Subjects with previously unstable brain lesions who have been definitively treated
with stereotactic radiation therapy, surgery or gamma knife therapy are eligible.
- Subjects with brain lesions who are untreated (i.e. newly discovered brain
lesions during screening) or received whole brain radiation must have documented
stable disease as assessed by two consecutive assessments ≥ 4 weeks apart and
have not required steroids for at least ≥ 4 weeks prior to randomization.
- Use of any live vaccines against infectious diseases within 3 months before
randomization.
- Active infection requiring systemic antibiotic therapy at time of randomization.
- Systemic chronic steroid therapy (˃ 10mg/day prednisone or equivalent) or any other
immunosuppressive therapy administered within 7 days prior to randomization. Note:
Local steroids such as topical, inhaled, nasal and ophthalmic steroids are allowed.
- Active, known or suspected autoimmune disease or a documented history of autoimmune
disease. Note: Subjects with vitiligo, controlled type I diabetes mellitus on stable
insulin dose, residual autoimmune-related hypothyroidism only requiring hormone
replacement or psoriasis not requiring systemic treatment or conditions not expected
to recur in the absence of an external trigger are permitted.
- Prior allogenic bone marrow or solid organ transplant
- History of known hypersensitivity to any of the investigational drugs used 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 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 (e.g targeted therapy, immunotherapy (e.g interferon,
checkpoint inhibitors or any other immunotherapy), chemotherapy and tumor vaccines).
- Medical history or current diagnosis of myocarditis
- Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-yes
