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

NCT03111992 | Completed Phase 1 FDA Drug

• 1 other identifier: CPDR001X2106
• Study Type: interventional
• Target: 26
• Locations: 4 countries
• Sites: 8

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.

Conditions

Multiple Myeloma

Keywords

Myeloma,; Multiple Myeloma,; Hematologic Diseases,; Myeloma, Multiple,; Myeloma-Multiple,; Programmed Cell Death 1 Receptor

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (10)

• Immunogenicity of PDR001 and CJM112

  First 6 months of study treatment

• Overall Response Rate (ORR)

  24 Months

• Best Overall Response (BOR)

  24 Months

• Progression Free Survival (PFS)

  24 Months

• Disease Control Rate (DCR)

  24 Months

Study Arms (3)

Arm A

EXPERIMENTAL

Dose escalation of single agent CJM112

Drug: CJM112

Arm B

EXPERIMENTAL

Dose escalation of CJM112 in combination with a fixed dose of PDR001

Drug: PDR001; Drug: CJM112

Arm C

EXPERIMENTAL

Dose escalation of LCL161 in combination with a fixed dose of PDR001

Drug: PDR001; Drug: LCL161

Interventions

PDR001 DRUG

Anti-PD1 antibody

Arm B; Arm C

CJM112 DRUG

Anti-IL-17A antibody

Arm A; Arm B

LCL161 DRUG

Oral small molecule SMAC-mimetic

Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Madrid, 28006, Spain

Location

Related Links

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

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Diseases

Interventions

spartalizumab; LCL161

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: April 13, 2017
• Study Start: December 18, 2017
• Primary Completion: March 2, 2020
• Study Completion: March 2, 2020
• Last Updated: February 9, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); DE (3); US (2); IT (1)