- Written informed consent must be obtained prior to any screening procedures
- Phase I part: Patients with advanced/metastatic solid tumors, with measurable or
non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who
have progressed despite standard therapy or are intolerant of standard therapy, or for
whom no standard therapy exists.
- Phase II part: Patients with advanced/metastatic solid tumors, with at least one
measurable lesion as determined by RECIST version 1.1, who have progressed following
their last prior therapy, and fit into one of the following groups:
- Group 1a and 1b: NSCLC:
Patients with NSCLC must have had disease recurrence or progression during or after no more
than one prior systemic chemotherapy regimen (platinum doublet-based) for advanced or
metastatic disease. Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib,
Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon
19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive
EGFR mutation testing has been performed, the tumor must not harbor any known activating
EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). All
patients must be tested for EGFR mutational status and, for ALK translocation status if no
mutation is detected in EGFR. Patients with ALK translocation-positive NSCLC must have had
disease progression following treatment with a corresponding inhibitor and no more than one
systemic chemotherapy regimen (platinum doublet-based), in any sequence.
- Group 2: Melanoma:
All patients must have been tested for BRAF mutations. Patients with V600 mutation positive
melanoma must have clinical or radiological evidence of disease progression during or after
treatment with a BRAF inhibitor alone or in combination with other agents.
- Group 3: Triple negatice breast cancer.
- Group 4: Anaplastic thyroid cancer
- Patients are not required to have received or progressed on a prior therapy.
- Patients must not be at short term risk for life threatening complications (such as
airway compromise or bleeding from locoregional or metastatic disease,).
- Chemoradiation and/or surgery should be considered prior to study entry for those
patients with locally advanced disease if those therapies are considered to be in the
best interest of the patient.
- ECOG Performance Status ≤ 1.
- Patients must have a site of disease amenable to biopsy, and be a candidate for
tumor biopsy. Patient must be willing to undergo a new tumor biopsy at baseline
or at molecular pre-screening if applicable, and during therapy on this study.
For patients in the phase II part of the study, exceptions may be granted after
documented discussion with Novartis. After a sufficient number of paired biopsies
are collected, the decision may be taken to stop the collection of biopsies.
- History of severe hypersensitivity reactions to other mAbs
- Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
- Active infection requiring systemic antibiotic therapy.
- HIV infection.
- Active HBV or HCV infection.
- Patients with ocular melanoma.
- Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For
cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas,
4 weeks washout period. For patients receiving anticancer immunotherapies such as
CTLA-4 antagonists, 6 weeks is indicated as the washout period.
- Prior PD-1- or PD-L1-directed therapy.
- Patients requiring chronic treatment with systemic steroid therapy, other than
replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled,
nasal and ophthalmic steroids are not prohibited.
- Patients receiving systemic treatment with any immunosuppressive medication (other
than steroids as described above).
- Use of any vaccines against infectious diseases (e.g. influenza, varicella,
pneumococcus) within 4 weeks of initiation of study treatment.
- Presence of ≥ CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and
ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy
Other protocol defined Inclusion/Exclusion may apply.