This multicenter, open-label dose-escalation study with an extension phase will evaluate the safety and pharmacokinetics of lumretuzumab in combination with pertuzumab and paclitaxel in participants with metastatic breast cancer expressing HER3 and HER2 protein. Cohorts of participants will receive escalating doses of lumretuzumab intravenously (IV) every three weeks (Q3W) in combination with pertuzumab 840 milligrams (mg) IV initial dose followed by 420 mg IV Q3W and paclitaxel 80 milligrams per square meter (mg/m\^2) IV weekly. After completion of dose-limiting toxicity period (21 days), the study will be conducted in two extension phase cohorts: Cohort 1 and Cohort 2. Enrollment in Extension Phase Cohort 2 will occur only upon completion of Extension Phase Cohort 1. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Paclitaxel IV infusion will be administered as per schedule described in individual arm.
Pertuzumab IV infusion will be administered as per schedule described in individual arm.
Lumretuzumab will be administered as per schedule described in individual arm.
Rigshospitalet, Onkologisk Klinik
København Ø, Denmark
Centre Francois Baclesse; Comite Sein
Caen, France
Institut régional du Cancer Montpellier
Montpellier, France
Institut Curie; Oncologie Medicale
Paris, France
Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
Toulouse, France
Universitaetsklinikum Essen; Westdeutsches Tumorzentrum; Innere Klinik (Tumorforschung)
Essen, Germany
University of Hannover; Medical School
Hanover, Germany
Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
Heidelberg, Germany
Hospital del Mar; Servicio de Oncologia
Barcelona, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain
...and 3 more locations
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Day 1 up to Day 21
Percentage of Participants With Adverse Events
Time frame: Baseline up to approximately 39 months
Percentage of Participants With Anti-Human Antibodies (HAHAs) to lumretuzumab [RO5479599]
Time frame: Pre-infusion (Pr-I) (0 hour [h]) on Day 1 (D1) of each Cycle (Cy) up to approximately 39 months (assessed at Pr-I on D1 of each treatment Cy up to 28 and 42-45 days after last infusion [up to approximately 39 months overall]) (1 Cy = 21 days)
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of lumretuzumab [RO5479599]
Time frame: Pr-I (0 Hr) & 3, 24, 72, 168, 264, 312, 432, & 480 Hr post D1 infusion (infusion duration = 1.5-2 hours) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)
Pharmacokinetics: Maximum Serum Concentration (Cmax) of lumretuzumab [RO5479599]
Time frame: Pr-I (0 Hr) & 3, 24, 72, 168, 264, 312, 432, & 480 Hr post D1 infusion (infusion duration = 1.5-2 hours) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)
Pharmacokinetics: Trough Serum Concentration (Ct) of lumretuzumab [RO5479599]
Time frame: Pr-I (0 h) on D1 of each cycles beginning from Cy 2 up to 28 and 42-45 days after last infusion (up to approximately 39 months) (1 Cy = 21 days)
Pharmacokinetics: Time to Reach Maximum Serum Concentration (tmax) of lumretuzumab [RO5479599]
Time frame: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 Hr post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)
Pharmacokinetics: Clearance (CL) of lumretuzumab [RO5479599]
Time frame: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 h post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)
Pharmacokinetics: Volume of distribution (V) of lumretuzumab [RO5479599]
Time frame: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 h post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)
Pharmacokinetics: Accumulation Ratio of lumretuzumab [RO5479599]
Time frame: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 h post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)
Pharmacokinetics: Elimination Half-Life (t1/2) of lumretuzumab [RO5479599]
Time frame: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 h post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)
Pharmacokinetics: Serum Concentration at the Time of Tumor Progression (Cprog) of lumretuzumab [RO5479599]
Time frame: At the time of tumor progression (up to approximately 39 months)
Pharmacokinetics: Serum Concentration at the Time of Tumor Response (Complete response [CR]/Partial Response [PR]) of lumretuzumab [RO5479599]
Time frame: At the time of tumor progression (up to approximately 39 months)
Pharmacokinetics: Serum Concentration at the Time of DLT of lumretuzumab [RO5479599]
Time frame: At the time of DLT (up to 21 days)
Pharmacokinetics: Serum Concentration at the Time of Tumor and Skin Biopsy (Cb) of lumretuzumab [RO5479599]
Time frame: At the time of tumor/skin biopsy (up to approximately 39 months)
Pharmacokinetics: Serum Concentration at the Time of Infusion-Related Reactions (IRR) of lumretuzumab [RO5479599]
Time frame: At the time of IRR (up to approximately 39 months)
Recommended Phase II Dose of lumretuzumab [RO5479599]
Time frame: Day 1 up to Day 21
Percentage of Participants With Best Overall Response of CR or PR (Objective Response) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1) Criteria
Time frame: Baseline up to documented disease progression (PD) or death, whichever occurs first up to approximately 39 months (assessed at baseline thereafter every 9 weeks up to 28 days after last infusion or early discontinuation)
Percentage of Participants With Best Overall Response of CR or PR or SD (Disease Control), Assessed Using RECIST V1.1 Criteria
Time frame: Baseline up to documented PD or death, whichever occurs first up to approximately 39 months (assessed at baseline thereafter every 9 weeks up to 28 days after last infusion or early discontinuation)
Duration of Response, Assessed Using RECIST V1.1 Criteria
Time frame: From first confirmed documented objective response (CR/PR) up to documented PD or death, whichever occurs first up to approximately 39 months (assessed at baseline thereafter every 9 weeks up to 28 days after last infusion or early discontinuation)
Progression-Free Survival Assessed Using RECIST V1.1 Criteria
Time frame: Baseline up to documented PD or death, whichever occurs first up to approximately 39 months (assessed at baseline thereafter every 9 weeks up to 28 days after last infusion or early discontinuation)
Overall Survival
Time frame: Baseline up to death (up to approximately 39 months)
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