Clinical Trials /

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

NCT03742349

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
spartalizumabPDR0011: spartalizumab + LAG525 + NIR178
LAG5251: spartalizumab + LAG525 + NIR178
NIR1781: spartalizumab + LAG525 + NIR178
capmatinibINC2802: spartalizumab +LAG525 +capmatinib
MCS1103: spartalizumab + LAG525 + MCS110
canakinumabACZ8854: 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

NameTypeDescriptionInterventions
1: spartalizumab + LAG525 + NIR178Experimentalphase Ib (escalation and expansion)
  • spartalizumab
  • LAG525
  • NIR178
2: spartalizumab +LAG525 +capmatinibExperimentalphase Ib (escalation and expansion)
  • spartalizumab
  • LAG525
  • capmatinib
3: spartalizumab + LAG525 + MCS110Experimentalphase Ib (escalation and expansion)
  • spartalizumab
  • LAG525
  • MCS110
4: spartalizumab +LAG525 +canakinumabExperimentalphase 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