Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma

• PDR001 (Drug): Anti-PD1 antibody
• CJM112 (Drug): Anti-IL-17A antibody
• LCL161 (Drug): Oral small molecule SMAC-mimetic

Primary outcomes

• Number of patients reporting dose limiting toxicities [2 months]: number of patients reporting dose limiting toxicity
• The number of patients who experience a treatment-related adverse event after being treated with a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161 [24 months]: Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
• The number of patients requiring interruptions after a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161 [24 months]: Frequency of patients requiring a dose interruption
• The number of patients treated with single agent CJM112, or PDR001 in combination with either CJM112 or LCL161, who discontinued treatment [24 months]: Frequency of patients discontinuing treatment.
• The number of patients requiring a dose reduction after a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161 [24 months]: Frequency of patients requiring a dose reduction.

Secondary outcomes

• Immunogenicity of PDR001 and CJM112 [First 6 months of study treatment]: Presence and/or concentration of anti-PDR001, and anti-CJM112 antibodies
• Overall Response Rate (ORR) [24 Months]: Determine ORR in each arm of the study
• Best Overall Response (BOR) [24 Months]: Determine BOR in each arm of the study
• Progression Free Survival (PFS) [24 Months]: Determine PFS in each arm of the study
• Disease Control Rate (DCR) [24 Months]: Determine DCR in each arm of the study
• AUC of PDR001, CJM112 and LCL161 [24 months]: AUC
• Cmax of PDR001, CJM112 and LCL161 [24 months]: Cmax
• Tmax of PDR001, CJM112 and LCL161 [24 months]: Tmax
• Half-life of PDR001, CJM112 and LCL161 [24 months]: Half-life
• Concentration vs time profile of PDR001, CJM112 and LCL161 [24 months]: Concentration vs time

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Must be able to provide written informed consent before any screening procedures.
* Male or female patients ≥18 years of age.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
* Patients with a confirmed diagnosis of multiple myeloma who have received two or more lines of therapy including an IMiD and PI, and are relapsed and/or refractory to their most recent line of therapy. Patients who have received a prior autologous bone marrow transplant and otherwise meet the inclusion criteria are eligible for this study.
* Must have measurable disease defined by at least 1 of the following 3 measurements:
* Serum M-protein ≥ 0.5 g/dL OR
* Urine M-protein ≥ 200 mg/24 hours OR
* Serum free light chain (FLC) > 100 mg/L of involved FLC
* All patients must be willing to undergo a mandatory serial bone marrow aspirate and/or biopsy at screening and subsequently following treatment for the assessment of biomarker/pharmacodynamics and disease status. Exceptions may be considered after documented discussion with Novartis.

Other inclusion criteria included in the protocol might apply.

Exclusion Criteria:

* Use of systemic chronic steroid therapy (≥10mg /day of prednisone or equivalent), or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal, or ophthalmic steroids are allowed.
* Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
* Active, known or suspected autoimmune disease other than patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur.
* Patients with prior known toxicity attributed to PD-1 or PDL-1 directed therapy, which led to discontinuation of these agents, will be excluded from the PDR001 containing arms of the study.
* Patients with prior known toxicity from IL-17A directed therapy, which led to discontinuation of the study treatment, will be excluded from CJM112 containing arms of the study.
* Any of the following clinical laboratory results during screening (i.e., within 28 days before the first dose of study treatment):

  * Absolute neutrophil count (ANC) < 1,000/mm3 without growth factor support within 7 days prior to testing
  * Platelet count < 75,000 mm3 without transfusion support within 7 days prior to testing
  * Bilirubin > 1.5 times the upper limit of the normal range (ULN)
  * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN
  * Calculated creatinine clearance < 30 ml/min according to Cockcroft-Gault equation Other exclusion criteria included in the protocol might apply.

• Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals