Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC) (TNBC)

A Randomized Phase II Study of MCS110 Combined With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)

To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and gemcitabine (carbo/gem) in advanced TNBC patients

Study Overview

• Status: Completed
• Conditions: Advanced Triple Negative Breast Cancer (TNBC) With High TAMs
• Intervention / Treatment: Drug: MCS110; Drug: carboplatin; Drug: gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Austria
  • Salzburg, Austria, 5020
    • Novartis Investigative Site
  • Vienna, Austria, 1090
    • Novartis Investigative Site
  • Vienna, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
• France
  • Paris, France, 75231
    • Novartis Investigative Site
  • Saint-Herblain Cédex, France, 44805
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10967
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Essen, Germany, 45136
    • Novartis Investigative Site
• Hong Kong
  • Hong Kong SAR, Hong Kong
    • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • Napoli, Italy, 80131
    • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28050
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• Turkey
  • Istanbul, Turkey, 35100
    • Novartis Investigative Site
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center SC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Adult women (≥ 18 years of age) with advanced TNBC.
• Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing, based on last available tumor tissue.
• ER/PgR negativity to follow local guidelines
• If IHC HER2 2+, a negative FISH test is required
• A pre-treatment tumor biopsy demonstrating high TAM content as assessed per the central laboratory
• Patients must have:

At least one measurable lesion per RECIST 1.1. (Note: Measurable lesions include lytic or mixed (lytic + blastic) bone lesions, with an identifiable soft tissue component that meets the measurability criteria)

Exclusion Criteria:

• Prior chemotherapy for advanced BC. Previous adjuvant/neoadjuvant chemotherapy is allowed (carboplatin, cisplatin or gemcitabine only if > 12 months has passed since last administration).
• Therapy for underlying malignancy within 2 weeks prior to start of study treatment:
• Chemotherapy, biologic therapy (antibodies and biologically targeted small molecules)
• Radiotherapy
• Major surgery
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroids (≥10 mg of prednisone or equivalent) at the time of first study dose.
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening.
• Known history of human immunodeficiency virus or active infection with hepatitis virus or any uncontrolled active systemic infection.
• Patients with the following laboratory values during screening and on Day 1 predose:
• Absolute Neutrophil Count (ANC) < 1.5x109/L
• Hemoglobin < 9 g/dL
• Platelets < 100x109/L
• Serum creatinine > 1.5 x ULN
• Serum total bilirubin > 1.5 x ULN
• AST/SGOT and ALT/SGPT > 3.0 x ULN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1: MCS110+carboplatin+gemcitabine; MCS110+carboplatin+gemcitabine	Drug: MCS110; taken by I.V; Drug: carboplatin; taken by I.V; Drug: gemcitabine; taken by I.V
ACTIVE_COMPARATOR: Arm 2: carboplatin+gemcitabine; carboplatin+gemcitabine	Drug: carboplatin; taken by I.V; Drug: gemcitabine; taken by I.V

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment)	PFS Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau	AUC tau derived from day 0 to 21 (cycle 1) from day 0 to 21 (cycle 4) Cycle duration is 21 days	day 21 (end cycle 1); day 84 (end cycle 4)
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax		day 21 (end cycle 1); day 84 (end cycle 4)
Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)	day 21 (end cycle 1); day 84 (end cycle 4)	day 21, day 84
AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)	day 21 (end cycle 1); day 84 (end cycle 4)	day 21, day 84
Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels	results expressed as a the ratio change from baseline expressed in percentage. Cycle duration is 21 days. These Biomarker Analyses were performed for MCS110 treated patients only.	baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148
Serum C-terminal Telopeptide of Type I Collagen (CTX-I)	results expressed as a the ratio change from baseline expressed in percentage. Cycle duration is 21 days. Biomarker Analyses performed for MCS110 treated patients only.	baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment)	CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR. Efficacy Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design.	4 years
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response	CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR. Efficacy Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design.	4 years
Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption	patients treated with MCS110 only	4 years
MCS110 Dose Intensity	Relative dose intensity by categories. Patients treated with MCS110 only. The dose intensity measures the dose actually taken versus the planned dose, and is expressed in percentage: <50%: less than 50 % of the planned dose received; 50-<75 %: dose received is 50% or more, but less than 75 %; 75-<90 %: dose received is 75% or more, but less than 90%; 90-<110 %: dose received is 90% or more, but less than 110%	4 years
Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies.	results expressed as a the ratio change from baseline expressed in percentage: Biopsies were taken at baseline and between Day 29 and Day 43. Patients treated with MCS110 only	Baseline, Day 29-43
Circulating Monocytes Cells in Blood	Cycle duration is 21 days results expressed in percentage of cells. Only 1 arm reported as results were available for 1 patient only.	day 15, 29, 43, 50

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 10, 2015
• Primary Completion (ACTUAL): January 4, 2020
• Study Completion (ACTUAL): March 23, 2020

Study Registration Dates

• First Submitted: April 22, 2015
• First Submitted That Met QC Criteria: May 5, 2015
• First Posted (ESTIMATE): May 6, 2015

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2021
• Last Update Submitted That Met QC Criteria: May 26, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: MCS110; carboplatin; gemcitabine; TNBC; TAMs
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Carboplatin
• Other Study ID Numbers: CMCS110Z2201; 2015-000179-29 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No