Description:
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.
Title
- Brief Title: Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).
- 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 IDs
- ORG STUDY ID:
CADPT01A12101C
- SECONDARY ID:
2018-002244-82
- NCT ID:
NCT03742349
Conditions
- Triple Negative Breast Cancer (TNBC)
Interventions
Drug | Synonyms | Arms |
---|
spartalizumab | PDR001 | 1: spartalizumab + LAG525 + NIR178 |
LAG525 | | 1: spartalizumab + LAG525 + NIR178 |
NIR178 | | 1: spartalizumab + LAG525 + NIR178 |
capmatinib | INC280 | 2: spartalizumab +LAG525 +capmatinib |
MCS110 | | 3: spartalizumab + LAG525 + MCS110 |
canakinumab | ACZ885 | 4: spartalizumab +LAG525 +canakinumab |
Purpose
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 Arms
Name | Type | Description | Interventions |
---|
1: spartalizumab + LAG525 + NIR178 | Experimental | phase Ib (escalation and expansion) | - spartalizumab
- LAG525
- NIR178
|
2: spartalizumab +LAG525 +capmatinib | Experimental | phase Ib (escalation and expansion) | - spartalizumab
- LAG525
- capmatinib
|
3: spartalizumab + LAG525 + MCS110 | Experimental | phase Ib (escalation and expansion) | - spartalizumab
- LAG525
- MCS110
|
4: spartalizumab +LAG525 +canakinumab | Experimental | phase Ib (escalation and expansion) | - spartalizumab
- LAG525
- canakinumab
|
Eligibility Criteria
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety |
Time Frame: | at month 18 |
Safety Issue: | |
Description: | Month 18 is assumed to be study end |
Secondary Outcome Measures
Measure: | Best overall response (BOR) |
Time Frame: | at month 18 |
Safety Issue: | |
Description: | Month 18 is assumed to be study end |
Measure: | Progression free survival (PFS) per RECIST v1.1 and iRECIST |
Time Frame: | at month 18 |
Safety Issue: | |
Description: | Month 18 is assumed to be study end |
Measure: | Presence of anti-spartalizumab antibodies |
Time Frame: | at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT |
Safety Issue: | |
Description: | |
Measure: | Presence of anti-LAG525 antibodies |
Time Frame: | at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT |
Safety Issue: | |
Description: | |
Measure: | Presence of anti-MCS110 antibodies |
Time Frame: | at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT |
Safety Issue: | |
Description: | |
Measure: | Presence of anti-canakinumab antibodies |
Time Frame: | at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT |
Safety Issue: | |
Description: | |
Measure: | Serum concentration of spartalizumab, LAG525, MCS110, canakinumab |
Time Frame: | 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 |
Safety Issue: | |
Description: | |
Measure: | Plasma concentration of NIR178, NJI675, capmatinib |
Time Frame: | at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT |
Safety Issue: | |
Description: | |
Measure: | PK parameter (Tmax) of spartalizumab |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Cmax) of spartalizumab |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (AUC) of spartalizumab |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Tmax) of LAG525 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Cmax) of LAG525 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (AUC) of LAG525 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Tmax) of NIR178 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Cmax) of NIR178 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (AUC) of NIR178 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Tmax) of capmatinib |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Cmax) of capmatinib |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (AUC) of capmatinib |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Tmax) of MCS110 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Cmax) of MCS110 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (AUC) of MCS110 |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Tmax) of canakinumab |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (Cmax) of canakinumab |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | PK parameter (AUC) of canakinumab |
Time Frame: | at month 12 |
Safety Issue: | |
Description: | cycle 12 |
Measure: | Changes from baseline of PD markers in tumor tissue (TILs, CD8, PD-L1, LAG-3) |
Time Frame: | at baseline and at Day 43 |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Phase Ib, TNBC, advanced, metastatic, immunotherapy, PDR001,
- LAG525, NIR178, INC280, MCS110, ACZ885
Last Updated
July 27, 2021