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Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).

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ClinicalTrials.gov Identifier: NCT03742349
Recruitment Status : Recruiting
First Posted : November 15, 2018
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE November 12, 2018
First Posted Date  ICMJE November 15, 2018
Last Update Posted Date September 10, 2019
Actual Study Start Date  ICMJE January 31, 2019
Estimated Primary Completion Date October 9, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 12, 2018)
  • Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end
  • Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end
  • Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only) [ Time Frame: at Day 28 ]
    end of first cycle
  • Frequency of dose interuptions [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end
  • Frequency of dose reductions [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end
  • Dose intensities [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03742349 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2018)
  • Best overall response (BOR) [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end
  • Progression free survival (PFS) per RECIST v1.1 and iRECIST [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end
  • Presence of anti-spartalizumab antibodies [ Time Frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT ]
  • Presence of anti-LAG525 antibodies [ Time Frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT ]
  • Presence of anti-MCS110 antibodies [ Time Frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT ]
  • Presence of anti-canakinumab antibodies [ Time Frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT ]
  • Serum concentration of spartalizumab, LAG525, MCS110, canakinumab [ Time Frame: at Day 1, Day 8, Day 15, Day 29, Day 57, Day 65, Day 70, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT ]
  • Plasma concentration of NIR178, NJI675, capmatinib [ Time Frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT ]
  • PK parameter (Tmax) of spartalizumab [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Cmax) of spartalizumab [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (AUC) of spartalizumab [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Tmax) of LAG525 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Cmax) of LAG525 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (AUC) of LAG525 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Tmax) of NIR178 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Cmax) of NIR178 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (AUC) of NIR178 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Tmax) of capmatinib [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Cmax) of capmatinib [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (AUC) of capmatinib [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Tmax) of MCS110 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Cmax) of MCS110 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (AUC) of MCS110 [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Tmax) of canakinumab [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (Cmax) of canakinumab [ Time Frame: at month 12 ]
    cycle 12
  • PK parameter (AUC) of canakinumab [ Time Frame: at month 12 ]
    cycle 12
  • Changes from baseline of PD markers in tumor tissue (TILs, CD8, PD-L1, LAG-3) [ Time Frame: at baseline and at Day 43 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).
Official Title  ICMJE A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Immunotherapy Combinations in Adult Patients With Triple-negative Breast Cancer
Brief Summary

This is a Phase Ib, open label, dose escalation study of spartalizumab + LAG525 in combination with NIR178, capmatinib, MCS110, or canakinumab, followed by a dose expansion in adult patients with advanced or metastatic TNBC.

During the dose-escalation part of each treatment arm, patients will be treated with fixed doses of spartalizumab + LAG525 in combination with partner investigational drugs to be escalated until the MTD is reached or a lower RDE is established: NIR178, capmatinib, MCS110, or canakinumab. It is anticipated that other partner study drugs may be added in the future by protocol amendment.

After the determination of the MTD/RDE for a particular treatment arm, dose expansion may begin in that arm in order to further assess safety, tolerability, PK/PD, and anti-tumor activity of each combination at the MTD/RDE. Dose expansion arms may initiate only after consideration by the Investigators and Novartis of all available toxicity information, the assessment of risk to future patients from the BLRM, and the available PK, preliminary efficacy, and PD information. There is no requirement for dose-escalation treatment arms reaching an MTD/RDE to proceed to dose expansion.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Cancer (TNBC)
Intervention  ICMJE
  • Biological: spartalizumab
    LIVI (Liquid in vial) Concentrate for Solution for infusion
    Other Name: PDR001
  • Biological: LAG525
    LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion
  • Drug: NIR178
    Capsule
  • Drug: capmatinib
    Tablet
    Other Name: INC280
  • Biological: MCS110
    LIVI (Liquid in vial) Concentrate for Solution for infusion
  • Biological: canakinumab
    LIVI (Liquid in vial) Solution for injection
    Other Name: ACZ885
Study Arms  ICMJE
  • Experimental: 1: spartalizumab + LAG525 + NIR178
    phase Ib (escalation and expansion)
    Interventions:
    • Biological: spartalizumab
    • Biological: LAG525
    • Drug: NIR178
  • Experimental: 2: spartalizumab +LAG525 +capmatinib
    phase Ib (escalation and expansion)
    Interventions:
    • Biological: spartalizumab
    • Biological: LAG525
    • Drug: capmatinib
  • Experimental: 3: spartalizumab + LAG525 + MCS110
    phase Ib (escalation and expansion)
    Interventions:
    • Biological: spartalizumab
    • Biological: LAG525
    • Biological: MCS110
  • Experimental: 4: spartalizumab +LAG525 +canakinumab
    phase Ib (escalation and expansion)
    Interventions:
    • Biological: spartalizumab
    • Biological: LAG525
    • Biological: canakinumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 12, 2018)
220
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 9, 2020
Estimated Primary Completion Date October 9, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  • Patients with advanced/metastatic TNBC (defined as HER-2 negative with <1% of tumor cell nuclei immunoreactive for estrogen receptor (ER) and progesterone receptor (PR)), with measurable disease as determined by RECIST version 1.1 (refer to Appendix 16.1). Tumor lesions previously irradiated or subjected to other loco-regional therapy will only be considered measurable if there is documented disease progression at the treated site prior to study entry.
  • Patients should have received standard chemotherapy for advanced or metastatic disease but should not have received more than 2 prior lines of chemotherapy. Neoadjuvant or adjuvant chemotherapy will count as one prior line.
  • Patients must have received prior systemic treatment that included taxane-based chemotherapy for neoadjuvant or metastatic disease.
  • Patients must have a site of disease amenable to core needle biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at screening, and during therapy on the study. Exceptions may be considered after documented discussion with Novartis. Patients with available archival tumor tissue obtained ≤6 months prior to study treatment initiation do not need to undergo a new tumor biopsy at screening, if the patient has not received any anti-cancer therapy since the biopsy was taken, and if adequate tissue is available.

Main exclusion criteria applicable to all treatment arms:

  • Patient has received prior treatment with anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (any line of therapy).
  • Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within 2 weeks prior to initiating study treatment.
  • History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
  • Impaired cardiac function or clinically significant cardiac disease.
  • HIV infection.
  • Patients with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, including those with inactive disease for patients receiving either capmatinib, MCS110 or canakinumab.
  • Active, known or suspected autoimmune disease.
  • History of or current interstitial lung disease or pneumonitis grade ≥ 2.
  • Subjects with tuberculosis (TB), for patients receiving either MCS110 or canakinumab.

Other eligibility criteria apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Hong Kong,   Israel,   Italy,   Japan,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03742349
Other Study ID Numbers  ICMJE CADPT01A12101C
2018-002244-82 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP