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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-001147-13 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:-
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:
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States | ||
| Oklahoma University Health Sciences Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40102759 | Derived | 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. |
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| 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. |
|
| 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) |
| Groups 1 to 4: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) 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: Half life (t1/2) 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: Trough concentration (Ctrough) of RO6870810 and Atezolizumab | 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. | 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 | 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 | 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 | 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) | 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) | 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 | 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) | 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 | Pre-dose Day 1, 21 Run-in period, Cycle 1; 6h post-dose Day 1 Run-in period, Cycle 1 |
| Oklahoma City |
| Oklahoma |
| 73104 |
| United States |
| Sarah Cannon Res Inst; TN Onc | Nashville | Tennessee | 37203 | United States |
| St Vincent's Hospital Sydney | Darlinghurst | New South Wales | 2010 | Australia |
| Peter MacCallum Cancer Centre; Medical Oncology | Melbourne | Victoria | 3000 | Australia |
| University Health Network; Princess Margaret Hospital; Medical Oncology Dept | Toronto | Ontario | M5G 2M9 | Canada |
| Rigshospitalet; Onkologisk Klinik | København Ø | 2100 | Denmark |
| Western General Hospital | Edinburgh | EH4 2XU | United Kingdom |
| Guys and St Thomas NHS Foundation Trust, Guys Hospital | London | SE1 9RT | United Kingdom |
| The Christie | Manchester | M20 4BX | United Kingdom |
| Churchill Hospital | Oxford | OX3 7LJ | United Kingdom |
| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| C000722237 | RO6870810 |
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