Triple Negative Breast Cancer (TNBC)Phase 1NCT03742349
Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).
A Phase 1 study testing spartalizumab, LAG525 and NIR178 in people with Triple Negative Breast Cancer (TNBC), run by Novartis Pharmaceuticals at 13 sites in 9 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer (TNBC)
- What is being tested?
- spartalizumab, LAG525 and NIR178
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 13 sitesin 9 countries
- Study dates
- 31 Jan 2019to 6 Feb 2023
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
13 sites in 9 countries.
13 sites in 9 countries
United States2 sites
Sarah Cannon Research Institute Sarah Cannon Research
Nashville, Tennessee, 37203
Columbia University Medical Center- New York Presbyterian Columbia
New York, New York, 10032
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
Singapore2 sites
Novartis Investigative Site
Singapore, 119074
Novartis Investigative Site
Singapore, 169610
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Valencia, Valencia, 46010
Hong Kong1 site
Novartis Investigative Site
Shatin, New Territories, Hong Kong
About this study
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
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)
- Being tested
- spartalizumab, LAG525, NIR178, capmatinib, MCS110
- Keywords
- Phase Ib, TNBC, advanced, metastatic, immunotherapy, PDR001,, LAG525, NIR178, INC280, MCS110, ACZ885
- Medical subject headings
- Triple Negative Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
spartalizumabBiological
Also called PDR001
LIVI (Liquid in vial) Concentrate for Solution for infusion
LAG525Biological
LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion
NIR178Drug
Capsule
capmatinibDrug
Also called INC280
Tablet
MCS110Biological
LIVI (Liquid in vial) Concentrate for Solution for infusion
canakinumabBiological
Also called ACZ885
LIVI (Liquid in vial) Solution for injection
| Study group | Role | What they receive |
|---|---|---|
| 1: spartalizumab + LAG525 + NIR178 | Experimental | phase Ib (escalation and expansion) Receives: Biological: spartalizumab; Biological: LAG525; Drug: NIR178 |
| 2: spartalizumab +LAG525 +capmatinib | Experimental | phase Ib (escalation and expansion) Receives: Biological: spartalizumab; Biological: LAG525; Drug: capmatinib |
| 3: spartalizumab + LAG525 + MCS110 | Experimental | phase Ib (escalation and expansion) Receives: Biological: spartalizumab; Biological: LAG525; Biological: MCS110 |
| 4: spartalizumab +LAG525 +canakinumab | Experimental | phase Ib (escalation and expansion) Receives: Biological: spartalizumab; Biological: LAG525; Biological: canakinumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Month 18 is assumed to be study end
Measured: 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
Measured: at month 18
Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)
end of first cycle
Measured: at Day 28
Frequency of dose interuptions
Month 18 is assumed to be study end
Measured: at month 18
Frequency of dose reductions
Month 18 is assumed to be study end
Measured: at month 18
Dose intensities
Month 18 is assumed to be study end
Measured: at month 18
Secondary outcomes (27)
Best overall response (BOR)
Month 18 is assumed to be study end
Measured: at month 18
Progression free survival (PFS) per RECIST v1.1 and iRECIST
Month 18 is assumed to be study end
Measured: at month 18
Presence of anti-spartalizumab antibodies
Measured: 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
Measured: 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
Measured: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Presence of anti-canakinumab antibodies
Measured: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Serum concentration of spartalizumab, LAG525, MCS110, canakinumab
Measured: 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
Plasma concentration of NIR178, NJI675, capmatinib
Measured: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
PK parameter (Tmax) of spartalizumab
cycle 12
Measured: at month 12
PK parameter (Cmax) of spartalizumab
cycle 12
Measured: at month 12
PK parameter (AUC) of spartalizumab
cycle 12
Measured: at month 12
PK parameter (Tmax) of LAG525
cycle 12
Measured: at month 12
PK parameter (Cmax) of LAG525
cycle 12
Measured: at month 12
PK parameter (AUC) of LAG525
cycle 12
Measured: at month 12
PK parameter (Tmax) of NIR178
cycle 12
Measured: at month 12
PK parameter (Cmax) of NIR178
cycle 12
Measured: at month 12
PK parameter (AUC) of NIR178
cycle 12
Measured: at month 12
PK parameter (Tmax) of capmatinib
cycle 12
Measured: at month 12
PK parameter (Cmax) of capmatinib
cycle 12
Measured: at month 12
PK parameter (AUC) of capmatinib
cycle 12
Measured: at month 12
PK parameter (Tmax) of MCS110
cycle 12
Measured: at month 12
PK parameter (Cmax) of MCS110
cycle 12
Measured: at month 12
PK parameter (AUC) of MCS110
cycle 12
Measured: at month 12
PK parameter (Tmax) of canakinumab
cycle 12
Measured: at month 12
PK parameter (Cmax) of canakinumab
cycle 12
Measured: at month 12
PK parameter (AUC) of canakinumab
cycle 12
Measured: at month 12
Changes from baseline of PD markers in tumor tissue (TILs, CD8, PD-L1, LAG-3)
Measured: at baseline and at Day 43
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2018
- Study start31 Jan 2019
- Primary completion6 Feb 2023
- Study completion6 Feb 2023
Why it stopped: This was a sponsor decision and was not a consequence of any safety concern
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast Cancer (TNBC)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03742349
- Sponsor's protocol ID
- CADPT01A12101C
- Other IDs
- 2018-002244-82, 2018
- Status last verified
- May 2025
- First submitted
- 12 Nov 2018
- Last updated
- 18 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No