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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03742349




Registration number
NCT03742349
Ethics application status
Date submitted
12/11/2018
Date registered
15/11/2018
Date last updated
19/01/2024

Titles & IDs
Public title
Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).
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
Secondary ID [1] 0 0
2018-002244-82
Secondary ID [2] 0 0
CADPT01A12101C
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple Negative Breast Cancer (TNBC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - spartalizumab
Other interventions - LAG525
Treatment: Drugs - NIR178
Treatment: Drugs - capmatinib
Other interventions - MCS110
Other interventions - 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)


Other interventions: spartalizumab
LIVI (Liquid in vial) Concentrate for Solution for infusion

Other interventions: LAG525
LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion

Treatment: Drugs: NIR178
Capsule

Treatment: Drugs: capmatinib
Tablet

Other interventions: MCS110
LIVI (Liquid in vial) Concentrate for Solution for infusion

Other interventions: canakinumab
LIVI (Liquid in vial) Solution for injection
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Timepoint [1] 0 0
at month 18
Primary outcome [2] 0 0
Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Timepoint [2] 0 0
at month 18
Primary outcome [3] 0 0
Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)
Timepoint [3] 0 0
at Day 28
Primary outcome [4] 0 0
Frequency of dose interuptions
Timepoint [4] 0 0
at month 18
Primary outcome [5] 0 0
Frequency of dose reductions
Timepoint [5] 0 0
at month 18
Primary outcome [6] 0 0
Dose intensities
Timepoint [6] 0 0
at month 18
Secondary outcome [1] 0 0
Best overall response (BOR)
Timepoint [1] 0 0
at month 18
Secondary outcome [2] 0 0
Progression free survival (PFS) per RECIST v1.1 and iRECIST
Timepoint [2] 0 0
at month 18
Secondary outcome [3] 0 0
Presence of anti-spartalizumab antibodies
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
Secondary outcome [4] 0 0
Presence of anti-LAG525 antibodies
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
Secondary outcome [5] 0 0
Presence of anti-MCS110 antibodies
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
Secondary outcome [6] 0 0
Presence of anti-canakinumab antibodies
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
Secondary outcome [7] 0 0
Serum concentration of spartalizumab, LAG525, MCS110, canakinumab
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
Secondary outcome [8] 0 0
Plasma concentration of NIR178, NJI675, capmatinib
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
Secondary outcome [9] 0 0
PK parameter (Tmax) of spartalizumab
Timepoint [9] 0 0
at month 12
Secondary outcome [10] 0 0
PK parameter (Cmax) of spartalizumab
Timepoint [10] 0 0
at month 12
Secondary outcome [11] 0 0
PK parameter (AUC) of spartalizumab
Timepoint [11] 0 0
at month 12
Secondary outcome [12] 0 0
PK parameter (Tmax) of LAG525
Timepoint [12] 0 0
at month 12
Secondary outcome [13] 0 0
PK parameter (Cmax) of LAG525
Timepoint [13] 0 0
at month 12
Secondary outcome [14] 0 0
PK parameter (AUC) of LAG525
Timepoint [14] 0 0
at month 12
Secondary outcome [15] 0 0
PK parameter (Tmax) of NIR178
Timepoint [15] 0 0
at month 12
Secondary outcome [16] 0 0
PK parameter (Cmax) of NIR178
Timepoint [16] 0 0
at month 12
Secondary outcome [17] 0 0
PK parameter (AUC) of NIR178
Timepoint [17] 0 0
at month 12
Secondary outcome [18] 0 0
PK parameter (Tmax) of capmatinib
Timepoint [18] 0 0
at month 12
Secondary outcome [19] 0 0
PK parameter (Cmax) of capmatinib
Timepoint [19] 0 0
at month 12
Secondary outcome [20] 0 0
PK parameter (AUC) of capmatinib
Timepoint [20] 0 0
at month 12
Secondary outcome [21] 0 0
PK parameter (Tmax) of MCS110
Timepoint [21] 0 0
at month 12
Secondary outcome [22] 0 0
PK parameter (Cmax) of MCS110
Timepoint [22] 0 0
at month 12
Secondary outcome [23] 0 0
PK parameter (AUC) of MCS110
Timepoint [23] 0 0
at month 12
Secondary outcome [24] 0 0
PK parameter (Tmax) of canakinumab
Timepoint [24] 0 0
at month 12
Secondary outcome [25] 0 0
PK parameter (Cmax) of canakinumab
Timepoint [25] 0 0
at month 12
Secondary outcome [26] 0 0
PK parameter (AUC) of canakinumab
Timepoint [26] 0 0
at month 12
Secondary outcome [27] 0 0
Changes from baseline of PD markers in tumor tissue (TILs, CD8, PD-L1, LAG-3)
Timepoint [27] 0 0
at baseline and at Day 43

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/02/2023
Sample size
Target
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
Tennessee
Country [3] 0 0
Hong Kong
State/province [3] 0 0
Shatin, New Territories
Country [4] 0 0
Israel
State/province [4] 0 0
Tel Aviv
Country [5] 0 0
Italy
State/province [5] 0 0
MI
Country [6] 0 0
Japan
State/province [6] 0 0
Chiba
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam
Country [8] 0 0
Singapore
State/province [8] 0 0
Singapore
Country [9] 0 0
Spain
State/province [9] 0 0
Catalunya
Country [10] 0 0
Spain
State/province [10] 0 0
Comunidad Valenciana

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03742349
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03742349