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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: CJM112; Drug: PDR001; Drug: LCL161

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Castilla Y Leon
    • Salamanca, Castilla Y Leon, Spain, 37007
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm A; Dose escalation of single agent CJM112	Drug: CJM112; Anti-IL-17A antibody
EXPERIMENTAL: Arm B; Dose escalation of CJM112 in combination with a fixed dose of PDR001	Drug: CJM112; Anti-IL-17A antibody; Drug: PDR001; Anti-PD1 antibody
EXPERIMENTAL: Arm C; Dose escalation of LCL161 in combination with a fixed dose of PDR001	Drug: PDR001; Anti-PD1 antibody; Drug: LCL161; Oral small molecule SMAC-mimetic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients reporting dose limiting toxicities	number of patients reporting dose limiting toxicity	2 months
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	Number of patients with treatment-related adverse events as assessed by CTCAE v4.0	24 months
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	Frequency of patients requiring a dose interruption	24 months
The number of patients treated with single agent CJM112, or PDR001 in combination with either CJM112 or LCL161, who discontinued treatment	Frequency of patients discontinuing treatment.	24 months
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	Frequency of patients requiring a dose reduction.	24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com
• Results for CPDR001X2106 can be found on the Novartis Clinical Trial Results Website.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2017
• Primary Completion (ACTUAL): March 2, 2020
• Study Completion (ACTUAL): March 2, 2020

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: April 7, 2017
• First Posted (ACTUAL): April 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Programmed Cell Death 1 Receptor; Myeloma,; Multiple Myeloma,; Hematologic Diseases,; Myeloma, Multiple,; Myeloma-Multiple,
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors; Spartalizumab
• Other Study ID Numbers: CPDR001X2106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No