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

Triple Negative Breast Cancer (TNBC) Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03742349
• Other study ID #: CADPT01A12101C
• Secondary ID: 2018-002244-82
• Status: Terminated
• Phase: Phase 1
• Start date: January 31, 2019
• Est. completion date: February 6, 2023

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 64
• Est. completion date: February 6, 2023
• Est. primary completion date: February 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer (TNBC)
• Triple Negative Breast Neoplasms

Intervention

Biological:
• spartalizumab
LIVI (Liquid in vial) Concentrate for Solution for infusion
• LAG525
LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion

Drug:
• NIR178
Capsule
• capmatinib
Tablet

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

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Westmead	New South Wales
Hong Kong	Novartis Investigative Site	Shatin, New Territories
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Japan	Novartis Investigative Site	Kashiwa	Chiba
Netherlands	Novartis Investigative Site	Amsterdam
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
United States	Sarah Cannon Research Institute Sarah Cannon Research	Nashville	Tennessee
United States	Columbia University Medical Center- New York Presbyterian Columbia	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Hong Kong,  Israel,  Italy,  Japan,  Netherlands,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)	end of first cycle	at Day 28
Primary	Frequency of dose interuptions	Month 18 is assumed to be study end	at month 18
Primary	Frequency of dose reductions	Month 18 is assumed to be study end	at month 18
Primary	Dose intensities	Month 18 is assumed to be study end	at month 18
Secondary	Best overall response (BOR)	Month 18 is assumed to be study end	at month 18
Secondary	Progression free survival (PFS) per RECIST v1.1 and iRECIST	Month 18 is assumed to be study end	at month 18
Secondary	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
Secondary	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
Secondary	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
Secondary	Presence of anti-canakinumab antibodies		at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Secondary	Serum concentration of spartalizumab, LAG525, MCS110, canakinumab		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
Secondary	Plasma concentration of NIR178, NJI675, capmatinib		at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Secondary	PK parameter (Tmax) of spartalizumab	cycle 12	at month 12
Secondary	PK parameter (Cmax) of spartalizumab	cycle 12	at month 12
Secondary	PK parameter (AUC) of spartalizumab	cycle 12	at month 12
Secondary	PK parameter (Tmax) of LAG525	cycle 12	at month 12
Secondary	PK parameter (Cmax) of LAG525	cycle 12	at month 12
Secondary	PK parameter (AUC) of LAG525	cycle 12	at month 12
Secondary	PK parameter (Tmax) of NIR178	cycle 12	at month 12
Secondary	PK parameter (Cmax) of NIR178	cycle 12	at month 12
Secondary	PK parameter (AUC) of NIR178	cycle 12	at month 12
Secondary	PK parameter (Tmax) of capmatinib	cycle 12	at month 12
Secondary	PK parameter (Cmax) of capmatinib	cycle 12	at month 12
Secondary	PK parameter (AUC) of capmatinib	cycle 12	at month 12
Secondary	PK parameter (Tmax) of MCS110	cycle 12	at month 12
Secondary	PK parameter (Cmax) of MCS110	cycle 12	at month 12
Secondary	PK parameter (AUC) of MCS110	cycle 12	at month 12
Secondary	PK parameter (Tmax) of canakinumab	cycle 12	at month 12
Secondary	PK parameter (Cmax) of canakinumab	cycle 12	at month 12
Secondary	PK parameter (AUC) of canakinumab	cycle 12	at month 12
Secondary	Changes from baseline of PD markers in tumor tissue (TILs, CD8, PD-L1, LAG-3)		at baseline and at Day 43

External Links

•   Study Results