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

NCT ID: NCT03742349

Last Updated: 2025-05-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-31

Study Completion Date

2023-02-06

Brief Summary

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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

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Conditions

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Triple Negative Breast Cancer (TNBC)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1: spartalizumab + LAG525 + NIR178

phase Ib (escalation and expansion)

Group Type EXPERIMENTAL

spartalizumab

Intervention Type BIOLOGICAL

LIVI (Liquid in vial) Concentrate for Solution for infusion

LAG525

Intervention Type BIOLOGICAL

LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion

NIR178

Intervention Type DRUG

Capsule

2: spartalizumab +LAG525 +capmatinib

phase Ib (escalation and expansion)

Group Type EXPERIMENTAL

spartalizumab

Intervention Type BIOLOGICAL

LIVI (Liquid in vial) Concentrate for Solution for infusion

LAG525

Intervention Type BIOLOGICAL

LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion

capmatinib

Intervention Type DRUG

Tablet

3: spartalizumab + LAG525 + MCS110

phase Ib (escalation and expansion)

Group Type EXPERIMENTAL

spartalizumab

Intervention Type BIOLOGICAL

LIVI (Liquid in vial) Concentrate for Solution for infusion

LAG525

Intervention Type BIOLOGICAL

LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion

MCS110

Intervention Type BIOLOGICAL

LIVI (Liquid in vial) Concentrate for Solution for infusion

4: spartalizumab +LAG525 +canakinumab

phase Ib (escalation and expansion)

Group Type EXPERIMENTAL

spartalizumab

Intervention Type BIOLOGICAL

LIVI (Liquid in vial) Concentrate for Solution for infusion

LAG525

Intervention Type BIOLOGICAL

LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion

canakinumab

Intervention Type BIOLOGICAL

LIVI (Liquid in vial) Solution for injection

Interventions

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spartalizumab

LIVI (Liquid in vial) Concentrate for Solution for infusion

Intervention Type BIOLOGICAL

LAG525

LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion

Intervention Type BIOLOGICAL

NIR178

Capsule

Intervention Type DRUG

capmatinib

Tablet

Intervention Type DRUG

MCS110

LIVI (Liquid in vial) Concentrate for Solution for infusion

Intervention Type BIOLOGICAL

canakinumab

LIVI (Liquid in vial) Solution for injection

Intervention Type BIOLOGICAL

Other Intervention Names

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PDR001 INC280 ACZ885

Eligibility Criteria

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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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Columbia University Medical Center- New York Presbyterian Columbia

New York, New York, United States

Site Status

Sarah Cannon Research Institute Sarah Cannon Research

Nashville, Tennessee, United States

Site Status

Novartis Investigative Site

Westmead, New South Wales, Australia

Site Status

Novartis Investigative Site

Shatin, New Territories, Hong Kong, Hong Kong

Site Status

Novartis Investigative Site

Tel Aviv, , Israel

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Kashiwa, Chiba, Japan

Site Status

Novartis Investigative Site

Amsterdam, , Netherlands

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Valencia, Valencia, Spain

Site Status

Countries

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United States Australia Hong Kong Israel Italy Japan Netherlands Singapore Spain

Related Links

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Other Identifiers

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2018-002244-82

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CADPT01A12101C

Identifier Type: -

Identifier Source: org_study_id

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