This is Phase IB, open label, non-randomized study designed to investigate the dose, safety, pharmacokinetics and anti-tumor activity of RO6870810 in combination with a fixed dose of atezolizumab. The study consists of four groups, Group 1 (Dose Escalation Group) and Group 2 (Sequential Dose Group), and Groups 3 and 4 (Expansion Groups), which will further evaluate the safety, pharmacokinetic, pharmacodynamic and preliminary clinical activity in patients with triple negaive breast cancer and/or ovarian cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks.
RO6870810 will be injected SC,at initial planned doses of 0.30, 0.45, or 0.65 mg/kg, QD for the first 14 days of a 21-day cycle.
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, United States
Sarah Cannon Res Inst; TN Onc
Nashville, Tennessee, United States
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia
Peter MacCallum Cancer Centre; Medical Oncology
Melbourne, Victoria, Australia
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, Canada
Rigshospitalet; Onkologisk Klinik
København Ø, Denmark
Western General Hospital
Edinburgh, United Kingdom
Guys and St Thomas NHS Foundation Trust, Guys Hospital
London, United Kingdom
The Christie
Manchester, United Kingdom
...and 1 more locations
Group 1: Percentage of Participants With Dose Limiting Toxicities (DLT)
Time frame: Cycle 1 (Day 21)
Groups 1 to 4: Percentage of Participants With Adverse Events (AEs)
Time frame: Up to 22 months
Groups 1 to 4: Percentage of Participants With Change in Vital Signs, Physical Findings, Electrocardiogram (ECG) and Laboratory Parameters
Time frame: Baseline up to follow-up visit (approximately 22 months)
Groups 3 and 4: Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Groups 1 to 4: Maximum concentration (Cmax) of RO6870810 (RO) and Atezolizumab (Ate)
Time frame: RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Groups 1 to 4: Time of maximum concentration (tmax) of RO6870810 and Atezolizumab
Time frame: RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Groups 1 to 4: Clearance (CL) or Apparent Clearance (CL/F) of RO6870810 and Atezolizumab
Time frame: RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Groups 1 to 4: Volume of Distribution (Vd) or Apparent Volume of Distribution (Vd/F) of RO6870810 and Atezolizumab
Time frame: RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Groups 1 to 4: Area Under the Plasma Concentration-Time Curve From Time Zero to End of the Dosing Interval (AUC0-tau) of RO6870810 and Atezolizumab
Time frame: RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Groups 1 to 4: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of RO6870810 and Atezolizumab
Time frame: RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Groups 1 to 4: Half life (t1/2) of RO6870810 and Atezolizumab
Time frame: RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Groups 1 to 4: Trough concentration (Ctrough) of RO6870810 and Atezolizumab
Time frame: Pre-dose at Cycle 2 and at the beginning of every subsequent even-number cycles (Up to 22 months)
Groups 1 and 2: Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Groups 1 to 4: Objective Response (OR) as per Immune-Modified RECIST
Time frame: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Groups 1 to 4: Duration of Response (DoR) as per RECIST v1.1 and Immune-Modified RECIST
Time frame: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Groups 1 to 4: Progression-Free Survival (PFS) per RECIST v1.1 and Immune-Modified RECIST
Time frame: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Groups 1 to 4: Overall Survival (OS)
Time frame: From the time of first dose of study treatment to the time of death from any cause (Up to 22 months)
Groups 1 to 4: Tumor Marker Assessments (CA-125, According to Modified Gynecologic Cancer InterGroup [GCIG] Guidelines,CEA, CA15-3 Changes)
Time frame: Day 1 of each cycle till end of treatment or disease progression or death from any cause (Up to 22 months)
Groups 1 to 4: Changes in CD11b Expression Levels Measurement in CD14+ Monocytes From Blood Association with Steady-State RO6870810 PK Drug Exposure
Time frame: Day 1, 8, 15, 21 of Run-in period , Cycle 1
Groups 1 to 4: Changes in Markers (e.g., PD-L1, CD8/Ki 67) in Tissue Biopsy Specimens by Immunohistochemistry (IHC)
Time frame: Day 1, 15, 21 of Run-in period, Cycle 1
Groups 1 to 4: Percentage of Participants With Transcript Profiling Assessment Receiving Combination Study Treatment
Time frame: Pre-dose Day 1, 21 Run-in period, Cycle 1; 6h post-dose Day 1 Run-in period, Cycle 1
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