A Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (PD-L1 Antibody) in Participants With Advanced Ovarian Cancer or Triple Negative Breast Cancer
NCT ID: NCT03292172
Last Updated: 2020-11-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE1
36 participants
INTERVENTIONAL
2017-11-08
2019-02-26
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Group 1 - Escalation Dose: RO6870810 + Atezolizumab
Participants will be administered escalating doses of RO6870810 (0.3 milligram per kilogram \[mg/kg\], 0.45 mg/kg, and 0.65 mg/kg) subcutaneously (SC) once daily (QD) along with fixed dose of atezolizumab 1200 mg intravenously (IV) on Day 1 of each cycle (21 day cycles), every 3 weeks. RO6870810 will be given during the first 14 days.
Atezolizumab
Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks.
RO6870810
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.
Group 2 - Sequential Dose: RO6870810 + Atezolizumab
Participants will be administered RO6870810 monotherapy (starting dose 0.30 mg/kg) during the first 14 days of 21-day Run-in period. Following the Run-in period, participants will continue to receive RO6870810 at the same dose in combination with fixed dose of atezolizumab 1200 mg IV every 3 weeks in 21-day cycles.
Atezolizumab
Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks.
RO6870810
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.
Group 3 - Expansion in TNBC Group: RO6870810 + Atezolizumab
Participants will be administered dose of RO6870810 established in Group 1 (either 0.3 mg/kg, 0.45 mg/kg, or 0.65 mg/kg) SC QD along with fixed dose of atezolizumab 1200 mg IV on Day 1 of each cycle (21 day cycles), every 3 weeks. RO6870810 will be given during the first 14 days.
Atezolizumab
Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks.
RO6870810
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.
Group 4 - Expansion in OC Group: RO6870810 + Atezolizumab
Participants will be administered dose of RO6870810 established in Group 1 (either 0.3 mg/kg, 0.45 mg/kg, or 0.65 mg/kg) SC QD along with fixed dose of atezolizumab 1200 mg IV on Day 1 of each cycle (21 day cycles), every 3 weeks. RO6870810 will be given during the first 14 days.
Atezolizumab
Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks.
RO6870810
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.
Interventions
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Atezolizumab
Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks.
RO6870810
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.
Eligibility Criteria
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Inclusion Criteria
* Group 3: Participants with histologically confirmed TNBC who have received either one or 2 prior systemic treatments for metastatic breast cancer, and who have documented disease progression on or after the most recent treatment
* Group 4: Recurrent ovarian cancer participant who have received no more than two prior lines of platinum therapy in the recurrent setting and have progressed within 9 months from the last platinum containing regimen
* Measurable disease by RECIST criteria version 1.1 prior to study drug administration
* Performance status of 0 or 1 on the eastern Cooperative Oncology Group (ECOG) scale
* Life expectancy, in the opinion of the Investigator, of at least 3 months
* Disease-free of active second/secondary or prior malignancies for =\> 2 years with the exception of squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast
* Willing to provide the protocol specified tumor biopsies
* Acceptable hematologic status, liver and renal function
* Groups 1 and 2: Participants who have received prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, may be enrolled, provided the following requirements are met:
* Minimum of 5 months from the last dose of anti-PD-1, anti-CTLA-4, anti-PD- L1 or CD137 agonist treatment
* No history of severe immune-related adverse effects from CD137 agonist, anti-CTLA-4, anti-PD-1 or anti-PD-L1 (NCI CTCAE Grade 3 and 4). Any toxicity related to the therapy must have resolved completely, no residual toxicity as assessed by NCI CTCAE (v4.03)
* Agree to use protocol defined methods of contraception - For all participants, the reliability of sexual abstinence must be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception
Exclusion Criteria
* Asymptomatic or symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* History of leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Participants with indwelling catheters are allowed.
* Uncontrolled or symptomatic hypercalcemia
* New York Heart Association Class III or IV cardiac disease, pericarditis, myocardial infarction within the past 6 months, unstable arrhythmia
* Fredericia-corrected QT interval (QTcF) \> 470 milli seconds (msec) (female) or \> 450 msec (male), or history of congenital long QT syndrome. Any electrocardiogram (ECG) abnormality, including pericarditis, which in the opinion of the Investigator would preclude safe participation in the study.
* Active, uncontrolled bacterial, viral, or fungal infections within 7 days of study entry requiring systemic therapy. Participants with active TB infection are excluded from the study.
* Known clinically important respiratory impairment
* History of major organ transplant
* History of an autologous or allogeneic bone marrow transplant
* Serious non-malignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
* Pregnant or nursing women
* Any systemic anticancer therapy within 3 weeks prior to Cycle 1 Day 1
* Any radiation treatment to metastatic site within \<= 14 days of Cycle 1 Day 1
* Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1 Day 1 or anticipation of need for major surgical procedure during the course of the study
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human or humanized antibodies or fusion proteins
* Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
* Active or history of autoimmune disease
* History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Positive test for Human immunodeficiency virus (HIV)
* Active hepatitis B or hepatitis C
* Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
* Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the first dose of study treatment and during the study
* Consumption of agents which strongly induce CYP3A4 enzyme, within 14 days prior to the first dose of study treatment and during the study
* Treatment with systemic immuno-stimulatory agents within 4 weeks or five half-lives of the drug (whichever is shorter) prior to the first dose of study treatment
* Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to the first dose of study treatment, or, anticipated requirement for systemic immunosuppressive medications during the trial
* History of allergic reactions attributed to components of the formulated product(s)
* Unwillingness or inability to comply with procedures required in this protocol
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Locations
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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
Churchill Hospital
Oxford, , United Kingdom
Countries
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References
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Marbach D, Brouer-Visser J, Brennan L, Wilson S, Davydov II, Staedler N, Duarte J, Martinez Quetglas I, Nuesch E, Canamero M, Chesne E, Au-Yeung G, Hamilton E, Lheureux S, Richardson DL, Spanggaard I, Gomes B, Franjkovic I, DeMario M, Kornacker M, Lechner K. Immune modulation in solid tumors: a phase 1b study of RO6870810 (BET inhibitor) and atezolizumab (PD-L1 inhibitor). BMC Cancer. 2025 Mar 18;25(1):500. doi: 10.1186/s12885-025-13851-4.
Other Identifiers
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2017-001147-13
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
NP39487
Identifier Type: -
Identifier Source: org_study_id