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

NCT03292172 | Terminated Phase 1 FDA Drug

• 2 other identifiers: NP394872017-001147-13
• Study Type: interventional
• Target: 36
• Locations: 5 countries
• Sites: 11

Brief 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. 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.

Conditions

Advanced Ovarian Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (4)

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

  Cycle 1 (Day 21)

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

  Up to 22 months

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

  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.

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

Secondary Outcomes (17)

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

  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

  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

  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

  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

  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)

Study Arms (4)

Group 1 - Escalation Dose: RO6870810 + Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: RO6870810

Group 2 - Sequential Dose: RO6870810 + Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: RO6870810

Group 3 - Expansion in TNBC Group: RO6870810 + Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: RO6870810

Group 4 - Expansion in OC Group: RO6870810 + Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: RO6870810

Interventions

Atezolizumab DRUG

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

Group 1 - Escalation Dose: RO6870810 + Atezolizumab; Group 2 - Sequential Dose: RO6870810 + Atezolizumab; Group 3 - Expansion in TNBC Group: RO6870810 + Atezolizumab; Group 4 - Expansion in OC Group: RO6870810 + Atezolizumab

RO6870810 DRUG

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 1 - Escalation Dose: RO6870810 + Atezolizumab; Group 2 - Sequential Dose: RO6870810 + Atezolizumab; Group 3 - Expansion in TNBC Group: RO6870810 + Atezolizumab; Group 4 - Expansion in OC Group: RO6870810 + Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (11)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Res Inst; TN Onc

Nashville, Tennessee, 37203, United States

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Peter MacCallum Cancer Centre; Medical Oncology

Melbourne, Victoria, 3000, Australia

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, SE1 9RT, United Kingdom

Location

The Christie

Manchester, M20 4BX, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40102759 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

atezolizumab; RO6870810

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 25, 2017
• Study Start: November 8, 2017
• Primary Completion: February 26, 2019
• Study Completion: February 26, 2019
• Last Updated: November 6, 2020

Record last verified: 2020-11

Locations

GB (4); CA (1); AU (2); US (3); DK (1)