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

A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Immunotherapy Combinations in Adult Patients With Triple-negative Breast Cancer

ClinicalTrials.gov Identifier: NCT03742349

Novartis Reference Number: CADPT01A12101C

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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 
Triple Negative Breast Cancer (TNBC)
Phase 
Phase 1
Overall status 
Recruiting
Enrollment count 
220 participants
Start date 
Jan 31, 2019
Completion date 
Jan 17, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Biological
spartalizumab
LIVI (Liquid in vial) Concentrate for Solution for infusion
Biological
LAG525
LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion
Drug
NIR178
Capsule
Drug
capmatinib
Tablet
Biological
MCS110
LIVI (Liquid in vial) Concentrate for Solution for infusion
Biological
canakinumab
LIVI (Liquid in vial) Solution for injection

Eligibility 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.

Study Locations

United States
Novartis Investigative Site
Recruiting
Boston, 02114
Massachusetts
United States
Novartis Investigative Site
Recruiting
New York, 10032
New York
United States
Novartis Investigative Site
Recruiting
Nashville, 37203
Tennessee
United States
Australia
Novartis Investigative Site
Recruiting
Westmead, 2145
New South Wales
Australia
Hong Kong
Novartis Investigative Site
Recruiting
Shatin, New Territories,
-
Hong Kong
Israel
Novartis Investigative Site
Recruiting
Tel Aviv, 6423906
-
Israel
Italy
Novartis Investigative Site
Recruiting
Milano, 20133
MI
Italy
Novartis Investigative Site
Recruiting
Milano, 20141
MI
Italy
Japan
Novartis Investigative Site
Recruiting
Kashiwa, 277 8577
Chiba
Japan
Netherlands
Novartis Investigative Site
Recruiting
Amsterdam, 1066 CX
-
Netherlands
Singapore
Novartis Investigative Site
Recruiting
Singapore, 119074
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, 169610
-
Singapore
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Valencia, 46010
Comunidad Valenciana
Spain

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]