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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03111992
• Other study ID #: CPDR001X2106
• Status: Completed
• Phase: Phase 1
• Start date: December 18, 2017
• Est. completion date: March 2, 2020

Study information

• Verified date: February 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 2, 2020
• Est. primary completion date: March 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Kiel
Italy	Novartis Investigative Site	Milano	MI
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Mayo Clinic Arizona	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients reporting dose limiting toxicities	number of patients reporting dose limiting toxicity	2 months
Primary	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
Primary	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
Primary	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
Primary	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	Immunogenicity of PDR001 and CJM112	Presence and/or concentration of anti-PDR001, and anti-CJM112 antibodies	First 6 months of study treatment
Secondary	Overall Response Rate (ORR)	Determine ORR in each arm of the study	24 Months
Secondary	Best Overall Response (BOR)	Determine BOR in each arm of the study	24 Months
Secondary	Progression Free Survival (PFS)	Determine PFS in each arm of the study	24 Months
Secondary	Disease Control Rate (DCR)	Determine DCR in each arm of the study	24 Months
Secondary	AUC of PDR001, CJM112 and LCL161	AUC	24 months
Secondary	Cmax of PDR001, CJM112 and LCL161	Cmax	24 months
Secondary	Tmax of PDR001, CJM112 and LCL161	Tmax	24 months
Secondary	Half-life of PDR001, CJM112 and LCL161	Half-life	24 months
Secondary	Concentration vs time profile of PDR001, CJM112 and LCL161	Concentration vs time	24 months

External Links

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