Open label multicenter Phase I/II study of the safety and efficacy of PDR001 administered to patients with advanced malignancies (CPDR001X2101)

* phase I part: Advanced/metastatic solid tumors, with (non)measurable disease, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
* Phase II part: Advanced/metastatic solid tumors, with at least one measurable lesion, who have received standard therapy or are intolerant of standard therapy, have progressed following their last prior therapy, and fit into one of the following groups: *
Group 1: NSCLC
Patients with NSCLC must have had disease recurrence or progression during or after one
prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease.
Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab).
Patients must have been tested for mutations affecting EGFR and ALK. Patients with a known mutation in one gene need not be tested for the other. Patients with ALK or EGFR-positive NSCLC must have had recurrent or progressive disease after treatment with the corresponding inhibitor and platinum doublet-based chemotherapy, in any sequence.
Group 2: Melanoma
Patients with melanoma must have clinical or radiological evidence of disease progression during or after: For patients with BRAF wild type disease, at least one cycle of systemic treatment for
advanced melanoma.
For patients with BRAF V600 mutation positive disease, treatment with a BRAF inhibitor
(alone or in combination with other agents) and at least one other systemic treatment
Group 3: Triple negative breast cancer
* ECOG performance status 0-1-2.
* Disease amenable to biopsy and a candidate for tumor biopsy according to the treating institution*s guidelines. Patient must be willing to undergo a new tumor biopsy at baseline, and during therapy on this study.
Group 4: Anaplastic thyroid cancer
* Patients are not required to have received or progressed on a prior therapy.
* Patients in this indication 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.

* Symptomatic CNS metastases or CNS metastases that require local CNS-directed therapy or increasing doses of corticosteroids within the prior 2 weeks.
* Out of range laboratory values (see protocol section 5.3).
* Impaired cardiac function or clinically significant cardiac disease e.g. congestive heart failure NYHA * 2), QTcF > 470 msec
* 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 to enroll.
* History of drug-induced pneumonitis or current pneumonitis.
* Active infection requirings ystemic antibiotic therapy
* HIV infection, active HBV or HCV infection
* Ocular melanoma
* Systemic anti-cancer therapy within 2-4 weeks of the first dose of study treatment.
Wash-out for anticancer immunotherapiessuch as CTLA-4 antagonists, 6 weeks is indicated
* Prior PD-1- or PD-L1-directed therapy.
* Treatment with systemic steroid therapy, other than in the setting of adrenal insufficiency, systemic immunosuppressive therapy.
* Vaccines against infectious diseases within 4 weeks of initiation of study treatment.
* Major surgery within 2 weeks. .
* Radiotherapy within 2 weeks, except for palliative radiotherapy to a limited field.
* CSF within 2 weeks.