Clinical trial NCT03111992: Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma
Official title: Phase I/Ib, Multi-center, Open-label, Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Relapsed and/or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Myeloma,
Multiple Myeloma,
Hematologic Diseases,
Myeloma, Multiple,
Myeloma-Multiple,
Programmed Cell Death 1 Receptor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-04-13
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is comprised of 3 treatment arms:

* Single agent CJM112 (Arm A)
* A fixed dose of PDR001 in combination with CJM112 (Arm B)
* A fixed dose of PDR001 in combination with LCL161 (Arm C)

Patients may switch from treatment on Arm A to the corresponding CJM112 dose level on Arm B at the time of disease progression if that dose level has been declared safe, and if patients do not have any DLTs on single agent CJM112. Otherwise, patients will switch to a lower dose level that has been declared safe. No other cross-over between treatment arms is allowed.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety, tolerability, and identify the recommended doses of single agent CJM112, and of CJM112 or LCL161 in combination with PDR001, in patients with relapsed and/or refractory multiple myeloma.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients reporting dose limiting toxicities
timeFrame: 2 months
measure: 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
timeFrame: 24 months
measure: 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
timeFrame: 24 months
measure: The number of patients treated with single agent CJM112, or PDR001 in combination with either CJM112 or LCL161, who discontinued treatment
timeFrame: 24 months
measure: 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
timeFrame: 24 months
Secondary outcomes:
measure: Immunogenicity of PDR001 and CJM112
timeFrame: First 6 months of study treatment
measure: Overall Response Rate (ORR)
timeFrame: 24 Months
measure: Best Overall Response (BOR)
timeFrame: 24 Months
measure: Progression Free Survival (PFS)
timeFrame: 24 Months
measure: Disease Control Rate (DCR)
timeFrame: 24 Months
measure: AUC of PDR001, CJM112 and LCL161
timeFrame: 24 months
measure: Cmax of PDR001, CJM112 and LCL161
timeFrame: 24 months
measure: Tmax of PDR001, CJM112 and LCL161
timeFrame: 24 months
measure: Half-life of PDR001, CJM112 and LCL161
timeFrame: 24 months
measure: Concentration vs time profile of PDR001, CJM112 and LCL161
timeFrame: 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: