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

NCT02435680 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CMCS110Z22012015-000179-29
• Study Type: interventional
• Target: 50
• Locations: 11 countries
• Sites: 20

Brief Summary

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

Conditions

Advanced Triple Negative Breast Cancer (TNBC) With High TAMs

Keywords

MCS110; carboplatin; gemcitabine; TNBC; TAMs

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau

  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, day 84

• AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)

  day 21, day 84

• Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels

  baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148

Study Arms (2)

Arm 1: MCS110+carboplatin+gemcitabine

EXPERIMENTAL

MCS110+carboplatin+gemcitabine

Drug: MCS110; Drug: carboplatin; Drug: gemcitabine

Arm 2: carboplatin+gemcitabine

ACTIVE COMPARATOR

carboplatin+gemcitabine

Drug: carboplatin; Drug: gemcitabine

Interventions

MCS110 DRUG

taken by I.V

Arm 1: MCS110+carboplatin+gemcitabine

carboplatin DRUG

taken by I.V

Arm 1: MCS110+carboplatin+gemcitabine; Arm 2: carboplatin+gemcitabine

gemcitabine DRUG

taken by I.V

Arm 1: MCS110+carboplatin+gemcitabine; Arm 2: carboplatin+gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Massachusetts General Hospital Cancer Center SC

Boston, Massachusetts, 02114, United States

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Salzburg, 5020, Austria

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Vienna, A-1090, Austria

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Paris, 75231, France

Location

Novartis Investigative Site

Saint-Herblain Cédex, 44805, France

Location

Novartis Investigative Site

Berlin, 10967, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Essen, 45136, Germany

Location

Novartis Investigative Site

Hong Kong SAR, Hong Kong

Location

Novartis Investigative Site

Bologna, 40138, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Istanbul, 35100, Turkey (Türkiye)

Location

MeSH Terms

Interventions

Carboplatin; Gemcitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: May 6, 2015
• Study Start: August 10, 2015
• Primary Completion: January 4, 2020
• Study Completion: March 23, 2020
• Last Updated: June 21, 2021
• Results First Posted: June 21, 2021

Record last verified: 2021-05

Locations

HK (1); AU (1); US (2); ES (4); TU (1); DE (3); BE (1); IT (2); FR (2); KR (2); TW (1)