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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 )

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.


Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer (TNBC) Biological: spartalizumab Biological: LAG525 Drug: NIR178 Drug: capmatinib Biological: MCS110 Biological: canakinumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Immunotherapy Combinations in Adult Patients With Triple-negative Breast Cancer
Actual Study Start Date : January 31, 2019
Estimated Primary Completion Date : October 9, 2020
Estimated Study Completion Date : October 9, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: 1: spartalizumab + LAG525 + NIR178
phase Ib (escalation and expansion)
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

Experimental: 2: spartalizumab +LAG525 +capmatinib
phase Ib (escalation and expansion)
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: capmatinib
Tablet
Other Name: INC280

Experimental: 3: spartalizumab + LAG525 + MCS110
phase Ib (escalation and expansion)
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

Biological: MCS110
LIVI (Liquid in vial) Concentrate for Solution for infusion

Experimental: 4: spartalizumab +LAG525 +canakinumab
phase Ib (escalation and expansion)
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

Biological: canakinumab
LIVI (Liquid in vial) Solution for injection
Other Name: ACZ885




Primary Outcome Measures :
  1. 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

  2. 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

  3. Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only) [ Time Frame: at Day 28 ]
    end of first cycle

  4. Frequency of dose interuptions [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end

  5. Frequency of dose reductions [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end

  6. Dose intensities [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end


Secondary Outcome Measures :
  1. Best overall response (BOR) [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end

  2. Progression free survival (PFS) per RECIST v1.1 and iRECIST [ Time Frame: at month 18 ]
    Month 18 is assumed to be study end

  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. PK parameter (Tmax) of spartalizumab [ Time Frame: at month 12 ]
    cycle 12

  10. PK parameter (Cmax) of spartalizumab [ Time Frame: at month 12 ]
    cycle 12

  11. PK parameter (AUC) of spartalizumab [ Time Frame: at month 12 ]
    cycle 12

  12. PK parameter (Tmax) of LAG525 [ Time Frame: at month 12 ]
    cycle 12

  13. PK parameter (Cmax) of LAG525 [ Time Frame: at month 12 ]
    cycle 12

  14. PK parameter (AUC) of LAG525 [ Time Frame: at month 12 ]
    cycle 12

  15. PK parameter (Tmax) of NIR178 [ Time Frame: at month 12 ]
    cycle 12

  16. PK parameter (Cmax) of NIR178 [ Time Frame: at month 12 ]
    cycle 12

  17. PK parameter (AUC) of NIR178 [ Time Frame: at month 12 ]
    cycle 12

  18. PK parameter (Tmax) of capmatinib [ Time Frame: at month 12 ]
    cycle 12

  19. PK parameter (Cmax) of capmatinib [ Time Frame: at month 12 ]
    cycle 12

  20. PK parameter (AUC) of capmatinib [ Time Frame: at month 12 ]
    cycle 12

  21. PK parameter (Tmax) of MCS110 [ Time Frame: at month 12 ]
    cycle 12

  22. PK parameter (Cmax) of MCS110 [ Time Frame: at month 12 ]
    cycle 12

  23. PK parameter (AUC) of MCS110 [ Time Frame: at month 12 ]
    cycle 12

  24. PK parameter (Tmax) of canakinumab [ Time Frame: at month 12 ]
    cycle 12

  25. PK parameter (Cmax) of canakinumab [ Time Frame: at month 12 ]
    cycle 12

  26. PK parameter (AUC) of canakinumab [ Time Frame: at month 12 ]
    cycle 12

  27. Changes from baseline of PD markers in tumor tissue (TILs, CD8, PD-L1, LAG-3) [ Time Frame: at baseline and at Day 43 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03742349


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, New York
Novartis Investigative Site Recruiting
New York, New York, United States, 10032
United States, Tennessee
Novartis Investigative Site Recruiting
Nashville, Tennessee, United States, 37203
Australia, New South Wales
Novartis Investigative Site Recruiting
Westmead, New South Wales, Australia, 2145
Hong Kong
Novartis Investigative Site Recruiting
Shatin, New Territories, Hong Kong
Israel
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 6423906
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20141
Japan
Novartis Investigative Site Recruiting
Kashiwa, Chiba, Japan, 277 8577
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1066 CX
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Valencia, Comunidad Valenciana, Spain, 46010
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03742349     History of Changes
Other Study ID Numbers: CADPT01A12101C
2018-002244-82 ( EudraCT Number )
First Posted: November 15, 2018    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Phase Ib, TNBC, advanced, metastatic, immunotherapy, PDR001,
LAG525, NIR178, INC280, MCS110, ACZ885
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Immunologic Factors
Antibodies, Monoclonal
Physiological Effects of Drugs