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Advanced Ovarian CancerPhase 1NCT03292172

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

A Phase 1 study testing Atezolizumab and RO6870810 in people with Advanced Ovarian Cancer and Triple Negative Breast Cancer, run by Hoffmann-La Roche at 11 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab and RO6870810
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
11 sitesin 5 countries
Study dates
8 Nov 2017to 26 Feb 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Groups 1 and 2: Participants with histologically confirmed advanced ovarian cancer or triple negative breast cancer who in the opinion of the Investigator are appropriate for this study
  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • Participants with history of prior malignancy except solid tumor treated curatively more than 3 years ago without evidence of recurrence
  • 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
Show all 32Show fewer
  • 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

Trial locations and contacts

11 sites in 5 countries.

11 sites in 5 countries

United Kingdom4 sites

  • Western General Hospital

    Edinburgh, EH4 2XU

  • Guys and St Thomas NHS Foundation Trust, Guys Hospital

    London, SE1 9RT

  • The Christie

    Manchester, M20 4BX

  • Churchill Hospital

    Oxford, OX3 7LJ

Other trials in United Kingdom

United States3 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Sarah Cannon Res Inst; TN Onc

    Nashville, Tennessee, 37203

  • Oklahoma University Health Sciences Center

    Oklahoma City, Oklahoma, 73104

Other trials in United States

Australia2 sites

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • Peter MacCallum Cancer Centre; Medical Oncology

    Melbourne, Victoria, 3000

Other trials in Australia

Canada1 site

  • University Health Network; Princess Margaret Hospital; Medical Oncology Dept

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Denmark1 site

  • Rigshospitalet; Onkologisk Klinik

    København Ø, 2100

Other trials in Denmark

About this study

Official title: Open Label, Dose Finding and Expansion Phase IB Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (Pd L1 Antibody) in Pateints With Advanced Ovarian Cancer or Triple Negative Breast Cancer

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.

Being tested
Atezolizumab, RO6870810
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks.

  • RO6870810Drug

    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.

Study groups in NCT03292172
Study groupRoleWhat they receive
Group 1 - Escalation Dose: RO6870810 + AtezolizumabExperimentalParticipants 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.
Receives: Drug: Atezolizumab; Drug: RO6870810
Group 2 - Sequential Dose: RO6870810 + AtezolizumabExperimentalParticipants 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.
Receives: Drug: Atezolizumab; Drug: RO6870810
Group 3 - Expansion in TNBC Group: RO6870810 + AtezolizumabExperimentalParticipants 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.
Receives: Drug: Atezolizumab; Drug: RO6870810
Group 4 - Expansion in OC Group: RO6870810 + AtezolizumabExperimentalParticipants 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.
Receives: Drug: Atezolizumab; Drug: RO6870810

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Group 1: Percentage of Participants With Dose Limiting Toxicities (DLT)

    Measured: Cycle 1 (Day 21)

  2. Groups 1 to 4: Percentage of Participants With Adverse Events (AEs)

    Measured: Up to 22 months

  3. Groups 1 to 4: Percentage of Participants With Change in Vital Signs, Physical Findings, Electrocardiogram (ECG) and Laboratory Parameters

    Measured: Baseline up to follow-up visit (approximately 22 months)

  4. Groups 3 and 4: Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

    Measured: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)

Secondary outcomes (17)

  1. Groups 1 to 4: Maximum concentration (Cmax) of RO6870810 (RO) and Atezolizumab (Ate)

    Measured: 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)

  2. Groups 1 to 4: Time of maximum concentration (tmax) of RO6870810 and Atezolizumab

    Measured: 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)

  3. Groups 1 to 4: Clearance (CL) or Apparent Clearance (CL/F) of RO6870810 and Atezolizumab

    Measured: 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)

  4. Groups 1 to 4: Volume of Distribution (Vd) or Apparent Volume of Distribution (Vd/F) of RO6870810 and Atezolizumab

    Measured: 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)

  5. 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

    Measured: 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)

  6. Groups 1 to 4: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of RO6870810 and Atezolizumab

    Measured: 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)

  7. Groups 1 to 4: Half life (t1/2) of RO6870810 and Atezolizumab

    Measured: 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)

  8. Groups 1 to 4: Trough concentration (Ctrough) of RO6870810 and Atezolizumab

    Measured: Pre-dose at Cycle 2 and at the beginning of every subsequent even-number cycles (Up to 22 months)

  9. Groups 1 and 2: Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

    Measured: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)

  10. Groups 1 to 4: Objective Response (OR) as per Immune-Modified RECIST

    Measured: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)

  11. Groups 1 to 4: Duration of Response (DoR) as per RECIST v1.1 and Immune-Modified RECIST

    Measured: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)

  12. Groups 1 to 4: Progression-Free Survival (PFS) per RECIST v1.1 and Immune-Modified RECIST

    Measured: From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)

  13. Groups 1 to 4: Overall Survival (OS)

    Measured: From the time of first dose of study treatment to the time of death from any cause (Up to 22 months)

  14. Groups 1 to 4: Tumor Marker Assessments (CA-125, According to Modified Gynecologic Cancer InterGroup [GCIG] Guidelines,CEA, CA15-3 Changes)

    Measured: Day 1 of each cycle till end of treatment or disease progression or death from any cause (Up to 22 months)

  15. Groups 1 to 4: Changes in CD11b Expression Levels Measurement in CD14+ Monocytes From Blood Association with Steady-State RO6870810 PK Drug Exposure

    Measured: Day 1, 8, 15, 21 of Run-in period , Cycle 1

  16. Groups 1 to 4: Changes in Markers (e.g., PD-L1, CD8/Ki 67) in Tissue Biopsy Specimens by Immunohistochemistry (IHC)

    Measured: Day 1, 15, 21 of Run-in period, Cycle 1

  17. Groups 1 to 4: Percentage of Participants With Transcript Profiling Assessment Receiving Combination Study Treatment

    Measured: Pre-dose Day 1, 21 Run-in period, Cycle 1; 6h post-dose Day 1 Run-in period, Cycle 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2017
  2. Study start8 Nov 2017
  3. Primary completion26 Feb 2019
  4. Study completion26 Feb 2019

Why it stopped: Portfolio prioritization

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03292172
Sponsor's protocol ID
NP39487
Other IDs
2017-001147-13, 2017
Status last verified
Nov 2020
First submitted
20 Sep 2017
Last updated
6 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40102759

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab and RO6870810 in people with Advanced Ovarian Cancer and Triple Negative Breast Cancer, run by Hoffmann-La Roche at 11 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United Kingdom, United States, Australia, Canada, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Portfolio prioritization). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Group 1: Percentage of Participants With Dose Limiting Toxicities (DLT) (time frame: Cycle 1 (Day 21)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03292172, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2020.

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