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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03111992
• Collaborator: (none)
• Enrollment: 26
• Locations: 8
• Arms: 3
• Actual Duration (Months): 26.4
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: PDR001; Drug: CJM112; Drug: LCL161	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• 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.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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 18, 2017
• Actual Primary Completion Date: Mar 2, 2020
• Actual Study Completion Date: Mar 2, 2020

Arms and Interventions

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: PDR001; Anti-PD1 antibody; Drug: CJM112; Anti-IL-17A 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

Outcome Measures

Primary Outcome Measures

1. Number of patients reporting dose limiting toxicities [2 months]

   number of patients reporting dose limiting toxicity

2. 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

3. 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

4. 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.

5. 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 Outcome Measures

1. Immunogenicity of PDR001 and CJM112 [First 6 months of study treatment]

   Presence and/or concentration of anti-PDR001, and anti-CJM112 antibodies

2. Overall Response Rate (ORR) [24 Months]

   Determine ORR in each arm of the study

3. Best Overall Response (BOR) [24 Months]

   Determine BOR in each arm of the study

4. Progression Free Survival (PFS) [24 Months]

   Determine PFS in each arm of the study

5. Disease Control Rate (DCR) [24 Months]

   Determine DCR in each arm of the study

6. AUC of PDR001, CJM112 and LCL161 [24 months]

   AUC

7. Cmax of PDR001, CJM112 and LCL161 [24 months]

   Cmax

8. Tmax of PDR001, CJM112 and LCL161 [24 months]

   Tmax

9. Half-life of PDR001, CJM112 and LCL161 [24 months]

   Half-life

10. Concentration vs time profile of PDR001, CJM112 and LCL161 [24 months]

    Concentration vs time

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Phoenix	Arizona	United States	85054
2	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
3	Novartis Investigative Site	Freiburg		Germany	79106
4	Novartis Investigative Site	Heidelberg		Germany	69120
5	Novartis Investigative Site	Kiel		Germany	24105
6	Novartis Investigative Site	Milano	MI	Italy	20133
7	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007
8	Novartis Investigative Site	Madrid		Spain	28006

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03111992
• Other Study ID Numbers: CPDR001X2106
• First Posted: Apr 13, 2017
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Myeloma,; Multiple Myeloma,; Hematologic Diseases,; Myeloma, Multiple,; Myeloma-Multiple,; Programmed Cell Death 1 Receptor
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Spartalizumab

Study Results

No Results Posted as of Feb 9, 2022