Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
MY TRIALS
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Register a trial
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03742349
Registration number
NCT03742349
Ethics application status
Date submitted
12/11/2018
Date registered
15/11/2018
Titles & IDs
Public title
Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).
Query!
Scientific 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
Query!
Secondary ID [1]
0
0
2018-002244-82
Query!
Secondary ID [2]
0
0
CADPT01A12101C
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Triple Negative Breast Cancer (TNBC)
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Breast
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Other - spartalizumab
Treatment: Other - LAG525
Treatment: Drugs - NIR178
Treatment: Drugs - capmatinib
Treatment: Other - MCS110
Treatment: Other - canakinumab
Experimental: 1: spartalizumab + LAG525 + NIR178 - phase Ib (escalation and expansion)
Experimental: 2: spartalizumab +LAG525 +capmatinib - phase Ib (escalation and expansion)
Experimental: 3: spartalizumab + LAG525 + MCS110 - phase Ib (escalation and expansion)
Experimental: 4: spartalizumab +LAG525 +canakinumab - phase Ib (escalation and expansion)
Treatment: Other: spartalizumab
LIVI (Liquid in vial) Concentrate for Solution for infusion
Treatment: Other: LAG525
LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion
Treatment: Drugs: NIR178
Capsule
Treatment: Drugs: capmatinib
Tablet
Treatment: Other: MCS110
LIVI (Liquid in vial) Concentrate for Solution for infusion
Treatment: Other: canakinumab
LIVI (Liquid in vial) Solution for injection
Query!
Intervention code [1]
0
0
Treatment: Other
Query!
Intervention code [2]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Query!
Assessment method [1]
0
0
Month 18 is assumed to be study end
Query!
Timepoint [1]
0
0
at month 18
Query!
Primary outcome [2]
0
0
Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Query!
Assessment method [2]
0
0
Month 18 is assumed to be study end
Query!
Timepoint [2]
0
0
at month 18
Query!
Primary outcome [3]
0
0
Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)
Query!
Assessment method [3]
0
0
end of first cycle
Query!
Timepoint [3]
0
0
at Day 28
Query!
Primary outcome [4]
0
0
Frequency of dose interuptions
Query!
Assessment method [4]
0
0
Month 18 is assumed to be study end
Query!
Timepoint [4]
0
0
at month 18
Query!
Primary outcome [5]
0
0
Frequency of dose reductions
Query!
Assessment method [5]
0
0
Month 18 is assumed to be study end
Query!
Timepoint [5]
0
0
at month 18
Query!
Primary outcome [6]
0
0
Dose intensities
Query!
Assessment method [6]
0
0
Month 18 is assumed to be study end
Query!
Timepoint [6]
0
0
at month 18
Query!
Secondary outcome [1]
0
0
Best overall response (BOR)
Query!
Assessment method [1]
0
0
Month 18 is assumed to be study end
Query!
Timepoint [1]
0
0
at month 18
Query!
Secondary outcome [2]
0
0
Progression free survival (PFS) per RECIST v1.1 and iRECIST
Query!
Assessment method [2]
0
0
Month 18 is assumed to be study end
Query!
Timepoint [2]
0
0
at month 18
Query!
Secondary outcome [3]
0
0
Presence of anti-spartalizumab antibodies
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Query!
Secondary outcome [4]
0
0
Presence of anti-LAG525 antibodies
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Query!
Secondary outcome [5]
0
0
Presence of anti-MCS110 antibodies
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Query!
Secondary outcome [6]
0
0
Presence of anti-canakinumab antibodies
Query!
Assessment method [6]
0
0
Query!
Timepoint [6]
0
0
at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Query!
Secondary outcome [7]
0
0
Serum concentration of spartalizumab, LAG525, MCS110, canakinumab
Query!
Assessment method [7]
0
0
Query!
Timepoint [7]
0
0
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
Query!
Secondary outcome [8]
0
0
Plasma concentration of NIR178, NJI675, capmatinib
Query!
Assessment method [8]
0
0
Query!
Timepoint [8]
0
0
at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Query!
Secondary outcome [9]
0
0
PK parameter (Tmax) of spartalizumab
Query!
Assessment method [9]
0
0
cycle 12
Query!
Timepoint [9]
0
0
at month 12
Query!
Secondary outcome [10]
0
0
PK parameter (Cmax) of spartalizumab
Query!
Assessment method [10]
0
0
cycle 12
Query!
Timepoint [10]
0
0
at month 12
Query!
Secondary outcome [11]
0
0
PK parameter (AUC) of spartalizumab
Query!
Assessment method [11]
0
0
cycle 12
Query!
Timepoint [11]
0
0
at month 12
Query!
Secondary outcome [12]
0
0
PK parameter (Tmax) of LAG525
Query!
Assessment method [12]
0
0
cycle 12
Query!
Timepoint [12]
0
0
at month 12
Query!
Secondary outcome [13]
0
0
PK parameter (Cmax) of LAG525
Query!
Assessment method [13]
0
0
cycle 12
Query!
Timepoint [13]
0
0
at month 12
Query!
Secondary outcome [14]
0
0
PK parameter (AUC) of LAG525
Query!
Assessment method [14]
0
0
cycle 12
Query!
Timepoint [14]
0
0
at month 12
Query!
Secondary outcome [15]
0
0
PK parameter (Tmax) of NIR178
Query!
Assessment method [15]
0
0
cycle 12
Query!
Timepoint [15]
0
0
at month 12
Query!
Secondary outcome [16]
0
0
PK parameter (Cmax) of NIR178
Query!
Assessment method [16]
0
0
cycle 12
Query!
Timepoint [16]
0
0
at month 12
Query!
Secondary outcome [17]
0
0
PK parameter (AUC) of NIR178
Query!
Assessment method [17]
0
0
cycle 12
Query!
Timepoint [17]
0
0
at month 12
Query!
Secondary outcome [18]
0
0
PK parameter (Tmax) of capmatinib
Query!
Assessment method [18]
0
0
cycle 12
Query!
Timepoint [18]
0
0
at month 12
Query!
Secondary outcome [19]
0
0
PK parameter (Cmax) of capmatinib
Query!
Assessment method [19]
0
0
cycle 12
Query!
Timepoint [19]
0
0
at month 12
Query!
Secondary outcome [20]
0
0
PK parameter (AUC) of capmatinib
Query!
Assessment method [20]
0
0
cycle 12
Query!
Timepoint [20]
0
0
at month 12
Query!
Secondary outcome [21]
0
0
PK parameter (Tmax) of MCS110
Query!
Assessment method [21]
0
0
cycle 12
Query!
Timepoint [21]
0
0
at month 12
Query!
Secondary outcome [22]
0
0
PK parameter (Cmax) of MCS110
Query!
Assessment method [22]
0
0
cycle 12
Query!
Timepoint [22]
0
0
at month 12
Query!
Secondary outcome [23]
0
0
PK parameter (AUC) of MCS110
Query!
Assessment method [23]
0
0
cycle 12
Query!
Timepoint [23]
0
0
at month 12
Query!
Secondary outcome [24]
0
0
PK parameter (Tmax) of canakinumab
Query!
Assessment method [24]
0
0
cycle 12
Query!
Timepoint [24]
0
0
at month 12
Query!
Secondary outcome [25]
0
0
PK parameter (Cmax) of canakinumab
Query!
Assessment method [25]
0
0
cycle 12
Query!
Timepoint [25]
0
0
at month 12
Query!
Secondary outcome [26]
0
0
PK parameter (AUC) of canakinumab
Query!
Assessment method [26]
0
0
cycle 12
Query!
Timepoint [26]
0
0
at month 12
Query!
Secondary outcome [27]
0
0
Changes from baseline of PD markers in tumor tissue (TILs, CD8, PD-L1, LAG-3)
Query!
Assessment method [27]
0
0
Query!
Timepoint [27]
0
0
at baseline and at Day 43
Query!
Eligibility
Key inclusion criteria
Main
* 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.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Single group
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Stopped early
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
31/01/2019
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
6/02/2023
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
64
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Westmead
Query!
Recruitment postcode(s) [1]
0
0
2145 - Westmead
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
New York
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Tennessee
Query!
Country [3]
0
0
Hong Kong
Query!
State/province [3]
0
0
Shatin, New Territories
Query!
Country [4]
0
0
Israel
Query!
State/province [4]
0
0
Tel Aviv
Query!
Country [5]
0
0
Italy
Query!
State/province [5]
0
0
MI
Query!
Country [6]
0
0
Japan
Query!
State/province [6]
0
0
Chiba
Query!
Country [7]
0
0
Netherlands
Query!
State/province [7]
0
0
Amsterdam
Query!
Country [8]
0
0
Singapore
Query!
State/province [8]
0
0
Singapore
Query!
Country [9]
0
0
Spain
Query!
State/province [9]
0
0
Catalunya
Query!
Country [10]
0
0
Spain
Query!
State/province [10]
0
0
Comunidad Valenciana
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
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.
Query!
Trial website
https://clinicaltrials.gov/study/NCT03742349
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03742349