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

Phase 2

Completed

• Conditions: Advanced Triple Negative Breast Cancer (TNBC) With High TAMs
• Interventions: Drug: MCS110; Drug: carboplatin; Drug: gemcitabine

• Registration Number: NCT02435680
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-04-22
• Study First Submitted QC: 2015-05-05
• Study First Posted: 2015-05-06
• Study Start: 2015-08-10
• Primary Completion: 2020-01-04
• Study Completion: 2020-03-23
• Results First Submitted: 2021-03-16
• Status Verified: 2021-05
• Results First Submitted QC: 2021-05-26
• Last Update Submitted: 2021-05-26
• Results First Posted: 2021-06-21
• Last Update Posted: 2021-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 50

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: MCS110+carboplatin+gemcitabine	carboplatin	MCS110+carboplatin+gemcitabine
Arm 1: MCS110+carboplatin+gemcitabine	gemcitabine	MCS110+carboplatin+gemcitabine
Arm 2: carboplatin+gemcitabine	carboplatin	carboplatin+gemcitabine
Arm 2: carboplatin+gemcitabine	gemcitabine	carboplatin+gemcitabine
Arm 1: MCS110+carboplatin+gemcitabine	MCS110	MCS110+carboplatin+gemcitabine

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau	day 21 (end cycle 1); day 84 (end cycle 4)	AUC tau derived from day 0 to 21 (cycle 1) from day 0 to 21 (cycle 4) Cycle duration is 21 days
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax	day 21 (end cycle 1); day 84 (end cycle 4)
MCS110 Dose Intensity	4 years	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%
Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies.	Baseline, Day 29-43	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
Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)	day 21, day 84	day 21 (end cycle 1); day 84 (end cycle 4)
Circulating Monocytes Cells in Blood	day 15, 29, 43, 50	Cycle duration is 21 days results expressed in percentage of cells. Only 1 arm reported as results were available for 1 patient only.
AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)	day 21, day 84	day 21 (end cycle 1); day 84 (end cycle 4)
Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels	baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148	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.
Serum C-terminal Telopeptide of Type I Collagen (CTX-I)	baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148	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.
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment)	4 years	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.
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response	4 years	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.
Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption	4 years	patients treated with MCS110 only

Trial Locations

Locations (3)

Highlands Oncology Group; 🇺🇸 Fayetteville, Arkansas, United States

Novartis Investigative Site; 🇹🇷 Istanbul, Turkey

Massachusetts General Hospital Cancer Center SC; 🇺🇸 Boston, Massachusetts, United States