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

NCT03742349 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CADPT01A12101C2018-002244-82
• Study Type: interventional
• Target: 64
• Locations: 9 countries
• Sites: 13

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.

Conditions

Triple Negative Breast Cancer (TNBC)

Keywords

Phase Ib, TNBC, advanced, metastatic, immunotherapy, PDR001,; LAG525, NIR178, INC280, MCS110, ACZ885

Outcome Measures

Primary Outcomes (6)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety

  Month 18 is assumed to be study end

  at month 18

• Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety

  Month 18 is assumed to be study end

  at month 18

• Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)

  end of first cycle

  at Day 28

• Frequency of dose interuptions

  Month 18 is assumed to be study end

  at month 18

• Frequency of dose reductions

  Month 18 is assumed to be study end

  at month 18

• Dose intensities

  Month 18 is assumed to be study end

  at month 18

Secondary Outcomes (27)

• Best overall response (BOR)

  at month 18

• Progression free survival (PFS) per RECIST v1.1 and iRECIST

  at month 18

• Presence of anti-spartalizumab antibodies

  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

  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

  at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT

Study Arms (4)

1: spartalizumab + LAG525 + NIR178

EXPERIMENTAL

phase Ib (escalation and expansion)

Biological: spartalizumab; Biological: LAG525; Drug: NIR178

2: spartalizumab +LAG525 +capmatinib

EXPERIMENTAL

phase Ib (escalation and expansion)

Biological: spartalizumab; Biological: LAG525; Drug: capmatinib

3: spartalizumab + LAG525 + MCS110

EXPERIMENTAL

phase Ib (escalation and expansion)

Biological: spartalizumab; Biological: LAG525; Biological: MCS110

4: spartalizumab +LAG525 +canakinumab

EXPERIMENTAL

phase Ib (escalation and expansion)

Biological: spartalizumab; Biological: LAG525; Biological: canakinumab

Interventions

spartalizumab BIOLOGICAL

LIVI (Liquid in vial) Concentrate for Solution for infusion

Also known as: PDR001

1: spartalizumab + LAG525 + NIR178; 2: spartalizumab +LAG525 +capmatinib; 3: spartalizumab + LAG525 + MCS110; 4: spartalizumab +LAG525 +canakinumab

LAG525 BIOLOGICAL

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

1: spartalizumab + LAG525 + NIR178; 2: spartalizumab +LAG525 +capmatinib; 3: spartalizumab + LAG525 + MCS110; 4: spartalizumab +LAG525 +canakinumab

NIR178 DRUG

Capsule

1: spartalizumab + LAG525 + NIR178

capmatinib DRUG

Tablet

Also known as: INC280

2: spartalizumab +LAG525 +capmatinib

MCS110 BIOLOGICAL

LIVI (Liquid in vial) Concentrate for Solution for infusion

3: spartalizumab + LAG525 + MCS110

canakinumab BIOLOGICAL

LIVI (Liquid in vial) Solution for injection

Also known as: ACZ885

4: spartalizumab +LAG525 +canakinumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Columbia University Medical Center- New York Presbyterian Columbia

New York, New York, 10032, United States

Location

Sarah Cannon Research Institute Sarah Cannon Research

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Shatin, New Territories, Hong Kong, Hong Kong

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Kashiwa, Chiba, 277 8577, Japan

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Related Links

• Study Results
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

spartalizumab; capmatinib; canakinumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2018
• First Posted: November 15, 2018
• Study Start: January 31, 2019
• Primary Completion: February 6, 2023
• Study Completion: February 6, 2023
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1); SG (2); NL (1); US (2); AU (1); JP (1); ES (2); HK (1); IT (2)