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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-003528-22 | EudraCT Number |
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This is an open-label, multi-center, randomized, Phase 1b, adaptive, clinical study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary therapeutic activity of RO6874281 in combination with atezolizumab with/without bevacizumab in participants with unresectable advanced and/or metastatic RCC. The study will consist of a dose-escalation part and an extension part.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Escalation Part (Arm A): Atezolizumab, RO6874281 | Experimental | Participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has complete response (CR), treatment may be discontinued and reintroduced if progressive disease (PD), for a maximum duration of 24 months. |
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| Escalation Part (Arm B): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Participants will receive RO6874281 in combination with atezolizumab and bevacizumab until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. |
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| Extension Part (Arm A): Atezolizumab, RO6874281 | Experimental | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part. Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) | The first patient in each cohort and regimen will be observed for safety for one week after the administration of RO6874281and atezolizumab +-bevacizumab, prior to enrollment of additional patients in a cohort. The DLT will be counted for each dose separately and each patient will contribute one single representative data point. | Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab |
| Maximum Tolerated Dose (MTD) of RO6874281 | The MTD is defined as the highest dose with less than 33% probability of dose limiting toxicity (DLT). | Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab |
| Recommended Dose of RO6874281 | The recommended dose is defined as the lowest safe dose with the best likelihood for clinical benefit. | Arm A: It ends one week after the second administration of RO6874281 + atezolizumab Arm B: one week after the first administration of RO6874281 + atezolizumab + bevacizumab |
| Percentage of Participants with Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Objective response rate (ORR) defined as the number of patients who achieved an objective response (partial response (PR) plus complete response (CR)) confirmed 28 or more days later, as determined by the Investigator using RECIST v1.1 and modified RECIST criteria at any time during the study divided by the number of response-evaluable patients. | Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Serum RO6874281 Concentration | Pre-infusion, 1 hour (hr) post start of infusion, end of infusion (EOI), 2, 6 hr post EOI on Cycle 1 Day 1; Cycle 1 Days 2, 3; Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 8; Cycle 1 Days 9, 10; Pre-infusion, EOI on Cycle 2 Day 1; Pre-infusion on Cycle 3 Day 1; Cycle 3 Day 2; Pre-infusion on Cycle 4 Day 1; Pre-infusion on Cycle 5 Day 1; Cycle 5 Day 2; Pre-infusion on Day 1; Day 2 in Cycle 9 and then every 4 cycles for the first year followed by every 6 cycles; treatment discontinuation; 28 days after last dose; 3 months after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 1, 2; -4 hr for other timepoints) (infusion length = 2 hr) (1 cycle = 15 days) |
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Inclusion criteria:
Adequate hematological function: neutrophil count of ≥1.5 ≥109 cells/L, platelet count of ≥100,000/≥L, Hb ≥9 g/dL (5.6 mmol/L), lymphocytes ≥0.8 ≥109 cells/L.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale Cancer Center; Medical Oncology | New Haven | Connecticut | 06520 | United States | ||
| Northwestern Center for Clinical Research; Cancer Center |
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| Extension Part (Arm B): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
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| Extension Part (Arm C): Atezolizumab, RO6874281 | Experimental | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
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| Extension Part (Arm D): Atezolizumab, Bevacizumab, RO6874281 | Experimental | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: Arm D is closed for future enrollment |
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| Bevacizumab | Drug | Arms A and B Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) after the atezolizumab administration, and prior to RO6874281 administration as an IV infusion on Days 15, 29, and once in 2 weeks from Day 29 onwards. In Arm D, Bevacizumab will be administered at a dose of 15mg/kg on Day 8 of Cycle 2 and on Day 8 of each consecutive cycle. |
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| RO6874281 | Drug | Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part. In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part |
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| Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| Area Under the Serum Concentration-Time Curve (AUC) for RO6874281 | Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 1; Cycle 1 Days 2, 3; Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 8; Cycle 1 Days 9, 10; Pre-infusion, EOI on Cycle 2 Day 1; Pre-infusion on Cycle 3 Day 1; Cycle 3 Day 2; Pre-infusion on Cycle 4 Day 1; Pre-infusion on Cycle 5 Day 1; Cycle 5 Day 2; Pre-infusion on Day 1; Day 2 in Cycle 9 and then every 4 cycles for the first year followed by every 6 cycles; treatment discontinuation; 28 days after last dose; 3 months after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 1, 2; -4 hr for other timepoints) (infusion length = 2 hr) (1 cycle = 15 days) | Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| Maximum Observed Serum Concentration (Cmax) of RO6874281 | Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 1; Cycle 1 Days 2, 3; Pre-infusion, 1 hr post start of infusion, EOI, 2, 6 hr post EOI on Cycle 1 Day 8; Cycle 1 Days 9, 10; Pre-infusion, EOI on Cycle 2 Day 1; Pre-infusion on Cycle 3 Day 1; Cycle 3 Day 2; Pre-infusion on Cycle 4 Day 1; Pre-infusion on Cycle 5 Day 1; Cycle 5 Day 2; Pre-infusion on Day 1; Day 2 in Cycle 9 and then every 4 cycles for the first year followed by every 6 cycles; treatment discontinuation; 28 days after last dose; 3 months after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 1, 2; -4 hr for other timepoints) (infusion length = 2 hr) (1 cycle = 15 days) | Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| Serum Atezolizumab Concentration | Pre-infusion, 0.5 hr post EOI on Cycle 1 Day 1; Pre-infusion on Cycle 1 Day 8; Pre-infusion on Day 1 Cycles 2, 3, 4, 5, and 9 onwards; treatment discontinuation; 28, 120 days after last dose (up to 60 months) (Pre-infusion = -4 hr) (infusion length = 1 hr) (1 cycle = 15 days) | Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| AUC of Atezolizumab | Pre-infusion, 0.5 hr post EOI on Cycle 1 Day 1; Pre-infusion on Cycle 1 Day 8; Pre-infusion on Day 1 Cycles 2, 3, 4, 5, and 9 onwards; treatment discontinuation; 28, 120 days after last dose (up to 60 months) (Pre-infusion = -4 hr) (infusion length = 1 hr) (1 cycle = 15 days) | Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| Cmax of Atezolizumab | Pre-infusion, 0.5 hr post EOI on Cycle 1 Day 1; Pre-infusion on Cycle 1 Day 8; Pre-infusion on Day 1 Cycles 2, 3, 4, 5, and 9 onwards; treatment discontinuation; 28, 120 days after last dose (up to 60 months) (Pre-infusion = -4 hr) (infusion length = 1 hr) (1 cycle = 15 days) | Pre-infusion on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| Serum Bevacizumab Concentration | Pre-infusion, 0.5 hr post EOI on Cycle 2 Day 1; Pre-infusion on Cycle 2 Day 8; Pre-infusion on Day 1 Cycles 3, 4, 5, and 9 onwards; treatment discontinuation; 28 days after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 2, 3; -4 hr for other timepoints) (infusion length = 1.5 hr) (1 cycle = 15 days) | Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| AUC of Bevacizumab | Pre-infusion, 0.5 hr post EOI on Cycle 2 Day 1; Pre-infusion on Cycle 2 Day 8; Pre-infusion on Day 1 Cycles 3, 4, 5, and 9 onwards; treatment discontinuation; 28 days after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 2, 3; -4 hr for other timepoints) (infusion length = 1.5 hr) (1 cycle = 15 days) | Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| Cmax of Bevacizumab | Pre-infusion, 0.5 hr post EOI on Cycle 2 Day 1; Pre-infusion on Cycle 2 Day 8; Pre-infusion on Day 1 Cycles 3, 4, 5, and 9 onwards; treatment discontinuation; 28 days after last dose (up to 60 months) (Pre-infusion = 0 hr for Day 1 Cycles 2, 3; -4 hr for other timepoints) (infusion length = 1.5 hr) (1 cycle = 15 days) | Pre-infusion on Cycle 2 Day 1 up to 60 months (detailed timeframe is provided in outcome measure description) |
| Percentage of Participants with Anti-Drug Antibodies (ADA) to RO6874281 | Baseline until 3 months post last dose of study treatment (assessed at pre-infusion on Days 1, 8 of Cycle 1; Pre-infusion on Day 1 of Cycles 2, 3, 4, 5, 9 and then every 4 cycles for the first year followed by every 6 cycles; treatment discontinuation; 28 days after last dose; 3 months after last dose [up to 60 months] [Pre-infusion = 0 hr for Day 1 Cycles 1, 2; -4 hr for other timepoints] [infusion length = 2 hr] [1 cycle = 15 days]) | Baseline until 3 months post last dose of study treatment (detailed timeframe is provided in outcome measure description) |
| Absolute Lymphocytes Count in Peripheral Blood | At baseline; Day 1, 2 3, 8 of Cycle 4. Day 1, 2 of Cycle 5 and Cycle 6. Day 1 of Cycle 7, Cycle 8 and Subsequent Cycles; At treatment discontinuation; 28 days after last dose; 3 months after last dose | Screening until 120 days post last dose of study treatment (up to 60 months) |
| Density of Lymphocytes in Tumor Samples | Archival biopsy: Baseline; Fresh biopsies: Baseline, Day 8 of Cycle 4; Optional biopsies: Any time during the study conduct (1 cycle = 15 days) (up to 60 months) |
| Percentage of Participants with Programmed Death-Ligand 1 (PD-L1) Status in Tumor Samples | Archival biopsy: Baseline; Fresh biopsies: Baseline, Day 8 of Cycle 4; Optional biopsies: Any time during the study conduct (1 cycle = 15 days) (up to 60 months) |
| Percentage of Participants with CR as Determined by the Investigator Using RECIST v1.1 | Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months) |
| Percentage of Participants with Disease Control as Determined by the Investigator Using RECIST v1.1 | Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months) |
| Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 | Screening until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months) |
| Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 | From randomization until disease progression or study treatment discontinuation (assessed at every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 24 months) |
| Overall Survival (OS) | From randomization until death (up to 60 months) |
| Chicago |
| Illinois |
| 60611 |
| United States |
| University of Maryland Greenebaum Comprehensive Cancer Center | Baltimore | Maryland | 21201 | United States |
| Princess Margaret Cancer Center | Toronto | Ontario | M5G 1Z5 | Canada |
| Herlev Hospital; Afdeling for Kræftbehandling | Herlev | 2730 | Denmark |
| Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes | Lyon | 69008 | France |
| Institut Claudius Regaud; Departement Oncologie Medicale | Toulouse | 31059 | France |
| Universitätsklinikum Tübingen; Klinik für Urologie | Tübingen | 72076 | Germany |
| Uniklinikum, Comprehensive Cancer Center Mainfranken; Interdisziplinäres Studienzentrum mit ECTU | Würzburg | 97078 | Germany |
| Universita di Modena e Reggio Emilia;Dipartimento di Oncologia ed Ematologia | Modena | Emilia-Romagna | 41100 | Italy |
| Fondazione IRCCS Policlinico San Matteo, Oncologia | Pavia | Lombardy | 27100 | Italy |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Samsung Medical Center | Seoul | 135-710 | South Korea |
| Clinica Universitaria de Navarra; Servicio de Oncologia | Pamplona | Navarre | 31008 | Spain |
| Hospital del Mar; Servicio de Oncologia | Barcelona | 08003 | Spain |
| Hospital Univ Vall d'Hebron; Servicio de Oncologia | Barcelona | 08035 | Spain |
| Hospital Clínic i Provincial; Servicio de Oncología | Barcelona | 08036 | Spain |
| Hospital Ramon y Cajal; Servicio de Oncologia | Madrid | 28034 | Spain |
| START Madrid-FJD, Hospital Fundacion Jimenez Diaz | Madrid | 28040 | Spain |
| Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia | Valencia | 46010 | Spain |
| Barts & London School of Med; Medical Oncology | London | EC1A 7BE | United Kingdom |
| The Christie | Manchester | M20 4BX | United Kingdom |
| Southampton General Hospital; Medical Oncology | Southampton | SO16 6YD | United Kingdom |
| ID | Term |
|---|---|
| D002292 | Carcinoma, Renal Cell |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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