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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003075-30 | EudraCT Number | ||
| RG7802 | Other Identifier | Roche |
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Study BP29541 is a first-in-human, open-label, multi-center, dose-escalation Phase I clinical study of single-agent RO6958688 in participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA) positive solid tumors who have progressed on standard treatment, are intolerant to standard of care (SOC), and/or are non-amenable to SOC. The study will be conducted in two parts. Part I of the study will investigate the safety and pharmacokinetics of a single dose of RO6958688 in single participant cohorts with dosing starting from a minimal anticipated biological effect level dose of 0.05 milligrams (mg) and up to a maximum dose of 2.5 mg. Part II will establish the appropriate therapeutic dose based on safety, pharmacokinetics, and the maximum tolerated dose (MTD) of RO6958688 for the once per week (QW) regimen, every three weeks (Q3W) regimen, and for the step up dosing regimen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I: RO6958688 | Experimental | Participants will receive single dose of RO6958688 starting from a dose of 0.05, 0.15, 0.45, 1.3, and 2.5 mg in Part I of the study. |
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| Part II: RO6958688 With/Without Obinutuzumab Pretreatment | Experimental | Participants will receive RO6958688 with or without obinutuzumab pretreatment QW, Q3W, or according to a combined QW/Q3W step up dosing schedule. Doses will start at 40mg and increase with each administration up to the MTD or 1200mg, whichever is lower. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RO6958688 | Drug | RO6958688 is given as an intravenous (IV) infusion as a single administration in Part I, and QW, Q3W, or as a combined QW/Q3W step up dosing regimen (cycle = 7 days in the QW regimen and cycle = 21 days in the Q3W regimen) in Part II of the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs) | Baseline up to 60 months | |
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) | Day 1 up to Day 21 | |
| Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO6958688 | Part I: Pre-dose (Hour 0) on Day 1 of Cycles 1, 2-3; 120 hours after end of infusion (EOI) in Cycle 1. Part II QW: pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4. Part II Q3W: pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4; 120 hours and 336 hours after EOI in Cycle 1, and 120 hours after EOI in Cycles 2, 3, 4. For Part I and II (QW and Q3W): pre-dose (Hour 0) on Day 1 of every cycle after Cycle 4 (Cycle 3 for Part I) up to treatment discontinuation (approximately 60 months), 28 days after last dose (approximately 60 months) (Cycle = 7 days for Part I and II QW; 21 days for Part II Q3W) (infusion duration = 30 minutes for Part I and 120 minutes for Part II [QW and Q3W]) | Pre-dose (Hour 0) on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome description section) |
| MTD of RO6958688 With/Without Obinutuzumab Pretreatment | Day 1 up to Day 21 | |
| Late Cycle MTD of RO6958688 Without Obinutuzumab Pretreatment for the Step up Dosing Regimen | Late cycle MTD is defined as the highest dose with less than or equal to DLT having been observed for 6 evaluable participants. If more than 6 participants are evaluable for DLT, late cycle MTD is the highest dose where less than (<) 33% of participants have DLT. | Day 1 up to Day 7 of each cycle as long as the dose is escalated weekly in Part II QW (up to approximately 60 months; Cycle = 7 days) |
| Maximum Serum Concentration (Cmax) for RO6958688 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 | Baseline up to 60 months (assessed at Screening, at 12 weeks [in Part I], at 8 weeks [in Part II QW and Q3W] after Cycle 1 Day 1, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death whichever occurs first, up to 60 months) (Cycle = 7 days for Part I and II QW, and 21 days for Part II Q3W) |
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Inclusion Criteria:
Exclusion Criteria:
Additional Exclusion Criteria for Participants to be Pretreated with Obinutuzumab:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars Sinai Medical Center; Samuel-Oschin Comprehensive Cancer Institute | Los Angeles | California | 90048 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36261015 | Derived | Martinez-Sabadell A, Morancho B, Rius Ruiz I, Roman Alonso M, Ovejero Romero P, Escorihuela M, Chicote I, Palmer HG, Nonell L, Alemany-Chavarria M, Klein C, Bacac M, Arribas J, Arenas EJ. The target antigen determines the mechanism of acquired resistance to T cell-based therapies. Cell Rep. 2022 Oct 18;41(3):111430. doi: 10.1016/j.celrep.2022.111430. |
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| Obinutuzumab | Drug | Obinutuzumab is given as an IV infusion at a dose level of 2000 mg on Day -13 or 1000 mg on Days -13 and -12 prior to the treatment start with RO6958688 on Cycle 1 Day 1. |
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| Tocilizumab | Drug | Tocilizumab will be administered as an IV infusion as necessary to treat adverse events. |
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Part I: Pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2-3; 24, 48, and 120 hours after EOI of Cycle 1. Part II QW: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24 and 120 hours after EOI of Cycles 1 and 2; 48 hours after EOI of Cycle 1. Part II Q3W: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24, 48, 120, and 336 hours after EOI of Cycle 1; 24 and 120 hours after EOI of Cycles 2, 3, and 4; 48 hours after EOI of Cycle 2. For Part I and II (QW and Q3W): pre-dose (Hour 0), EOI, 2 hours after EOI (only for Part I) on Day 1 of every cycle after Cycle 4 (Cycle 3 for Part I), 2 hours after EOI on Day 1 of Cycles 8 and 12 (only for Part II QW) up to treatment discontinuation (approximately 60 months), 28 days after last dose (approximately 60 months) (Cycle =7 days for Part I and II QW; 21 days for Part II Q3W) (infusion duration = 30 minutes for Part I and 120 minutes for Part II [QW and Q3W])
| Pre-dose (Hour 0) on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome description section) |
| Area Under the Concentration-Time Curve (AUC) for RO6958688 | Part I: Pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2-3; 24, 48, and 120 hours after EOI of Cycle 1. Part II QW: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24 and 120 hours after EOI of Cycles 1 and 2; 48 hours after EOI of Cycle 1. Part II Q3W: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24, 48, 120, and 336 hours after EOI of Cycle 1; 24 and 120 hours after EOI of Cycles 2, 3, and 4; 48 hours after EOI of Cycle 2. For Part I and II (QW and Q3W): pre-dose (Hour 0), EOI, 2 hours after EOI (only for Part I) on Day 1 of every cycle after Cycle 4 (Cycle 3 for Part I), 2 hours after EOI on Day 1 of Cycles 8 and 12 (only for Part II QW) up to treatment discontinuation (approximately 60 months), 28 days after last dose (approximately 60 months) (Cycle =7 days for Part I and II QW; 21 days for Part II Q3W) (infusion duration = 30 minutes for Part I and 120 minutes for Part II [QW and Q3W]) | Pre-dose (Hour 0) on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome description section) |
| Half-Life (t1/2) of RO6958688 | Part I: Pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2-3; 24, 48, and 120 hours after EOI of Cycle 1. Part II QW: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24 and 120 hours after EOI of Cycles 1 and 2; 48 hours after EOI of Cycle 1. Part II Q3W: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24, 48, 120, and 336 hours after EOI of Cycle 1; 24 and 120 hours after EOI of Cycles 2, 3, and 4; 48 hours after EOI of Cycle 2. For Part I and II (QW and Q3W): pre-dose (Hour 0), EOI, 2 hours after EOI (only for Part I) on Day 1 of every cycle after Cycle 4 (Cycle 3 for Part I), 2 hours after EOI on Day 1 of Cycles 8 and 12 (only for Part II QW) up to treatment discontinuation (approximately 60 months), 28 days after last dose (approximately 60 months) (Cycle =7 days for Part I and II QW; 21 days for Part II Q3W) (infusion duration = 30 minutes for Part I and 120 minutes for Part II [QW and Q3W]) | Pre-dose (Hour 0) on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome description section) |
| Clearance (CL) of RO6958688 | Part I: Pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2-3; 24, 48, and 120 hours after EOI of Cycle 1. Part II QW: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24 and 120 hours after EOI of Cycles 1 and 2; 48 hours after EOI of Cycle 1. Part II Q3W: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24, 48, 120, and 336 hours after EOI of Cycle 1; 24 and 120 hours after EOI of Cycles 2, 3, and 4; 48 hours after EOI of Cycle 2. For Part I and II (QW and Q3W): pre-dose (Hour 0), EOI, 2 hours after EOI (only for Part I) on Day 1 of every cycle after Cycle 4 (Cycle 3 for Part I), 2 hours after EOI on Day 1 of Cycles 8 and 12 (only for Part II QW) up to treatment discontinuation (approximately 60 months), 28 days after last dose (approximately 60 months) (Cycle =7 days for Part I and II QW; 21 days for Part II Q3W) (infusion duration = 30 minutes for Part I and 120 minutes for Part II [QW and Q3W]) | Pre-dose (Hour 0) on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome description section) |
| Volume of Distribution at Steady State (Vss) of RO6958688 | Part I: Pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2-3; 24, 48, and 120 hours after EOI of Cycle 1. Part II QW: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24 and 120 hours after EOI of Cycles 1 and 2; 48 hours after EOI of Cycle 1. Part II Q3W: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24, 48, 120, and 336 hours after EOI of Cycle 1; 24 and 120 hours after EOI of Cycles 2, 3, and 4; 48 hours after EOI of Cycle 2. For Part I and II (QW and Q3W): pre-dose (Hour 0), EOI, 2 hours after EOI (only for Part I) on Day 1 of every cycle after Cycle 4 (Cycle 3 for Part I), 2 hours after EOI on Day 1 of Cycles 8 and 12 (only for Part II QW) up to treatment discontinuation (approximately 60 months), 28 days after last dose (approximately 60 months) (Cycle =7 days for Part I and II QW; 21 days for Part II Q3W) (infusion duration = 30 minutes for Part I and 120 minutes for Part II [QW and Q3W]) | Pre-dose (Hour 0) on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome description section) |
| Minimum Drug Concentration (Cmin) for RO6958688 | Part I: Pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2-3; 24, 48, and 120 hours after EOI of Cycle 1. Part II QW: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24 and 120 hours after EOI of Cycles 1 and 2; 48 hours after EOI of Cycle 1. Part II Q3W: pre-dose (Hour 0), EOI, 2 hours after EOI on Day 1 of Cycles 1, 2, 3, and 4; 24, 48, 120, and 336 hours after EOI of Cycle 1; 24 and 120 hours after EOI of Cycles 2, 3, and 4; 48 hours after EOI of Cycle 2. For Part I and II (QW and Q3W): pre-dose (Hour 0), EOI, 2 hours after EOI (only for Part I) on Day 1 of every cycle after Cycle 4 (Cycle 3 for Part I), 2 hours after EOI on Day 1 of Cycles 8 and 12 (only for Part II QW) up to treatment discontinuation (approximately 60 months), 28 days after last dose (approximately 60 months) (Cycle =7 days for Part I and II QW; 21 days for Part II Q3W) (infusion duration = 30 minutes for Part I and 120 minutes for Part II [QW and Q3W]) | Pre-dose (Hour 0) on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in outcome description section) |
| Cmax for Obinutuzumab | Screening (pre-obinutuzumab dose [Hour 0] and EOI on Day -13 or Days -13 and -12), pre-RO6958688 dose [Hour 0] on Day 1 of Cycles 1, 2, 4, 8, and 12 in Part II QW (Cycle = 7 days) |
| Cmin for Obinutuzumab | Screening (pre-obinutuzumab dose [Hour 0] and EOI on Day -13 or Days -13 and -12), pre-RO6958688 dose [Hour 0] on Day 1 of Cycles 1, 2, 4, 8, and 12 in Part II QW (Cycle = 7 days) |
| Baseline up to 60 months (detailed timeframe is provided in outcome description section) |
| Duration of Response (DOR) According to RECIST v1.1 | Baseline up to 60 months (assessed at Screening, at 12 weeks [in Part I], at 8 weeks [in Part II QW and Q3W] after Cycle 1 Day 1, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death whichever occurs first, up to 60 months) (Cycle = 7 days for Part I and II QW, and 21 days for Part II Q3W) | Baseline up to 60 months (detailed timeframe is provided in outcome description section) |
| Percentage of Participants With Stable Disease (SD) According to RECIST v1.1 | Baseline up to 60 months (assessed at Screening, at 12 weeks [in Part I], at 8 weeks [in Part II QW and Q3W] after Cycle 1 Day 1, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death whichever occurs first, up to 60 months) (Cycle = 7 days for Part I and II QW, and 21 days for Part II Q3W) | Baseline up to 60 months (detailed timeframe is provided in outcome description section) |
| Percentage of Participants With Disease Control, Defined as PR+CR+SD, According to RECIST v1.1 | Baseline up to 60 months (assessed at Screening, at 12 weeks [in Part I], at 8 weeks [in Part II QW and Q3W] after Cycle 1 Day 1, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death whichever occurs first, up to 60 months) (Cycle = 7 days for Part I and II QW, and 21 days for Part II Q3W) | Baseline up to 60 months (detailed timeframe is provided in outcome description section) |
| Progression-Free Survival (PFS) According to RECIST v1.1 | From the first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months) |
| Change From Baseline in Activated Intra-Tumoral Cells | Baseline, Day 1 of Cycles 2, 3, 4, or 7 in Part II QW and Q3W (Cycle = 7 days for Part II QW and 21 days for Part II Q3W) |
| Best Overall Response (BOR) | Baseline up to 60 months (assessed at Screening, at 12 weeks [in Part I], at 8 weeks [in Part II QW and Q3W] after Cycle 1 Day 1, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death whichever occurs first, up to 60 months) (Cycle = 7 days for Part I and II QW, and 21 days for Part II Q3W) | Baseline up to 60 months (detailed timeframe is provided in outcome description section) |
| Stanford University |
| Palo Alto |
| California |
| 94305 |
| United States |
| UCLA Cancer Center | Santa Monica | California | 90404 | United States |
| University Of Colorado | Aurora | Colorado | 80045 | United States |
| Yale Cancer Center; Medical Oncology | New Haven | Connecticut | 06520 | United States |
| Dana Farber - Harvard | Boston | Massachusetts | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Sarah Cannon Cancer Center | Germantown | Tennessee | 38138 | United States |
| Princess Margaret Cancer Center | Toronto | Ontario | M5G 1Z5 | Canada |
| Rigshospitalet; Onkologisk Klinik | København Ø | 2100 | Denmark |
| Centre Leon Berard; Departement Oncologie Medicale | Lyon | 69373 | France |
| IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative | Naples | Campania | 80131 | Italy |
| Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica | Siena | Tuscany | 53100 | Italy |
| Antoni van Leeuwenhoek Ziekenhuis | Amsterdam | 1066 CX | Netherlands |
| 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 |
| START Madrid-FJD, Hospital Fundacion Jimenez Diaz | Madrid | 28040 | Spain |
| Hospital Universitario 12 de Octubre; Servicio de Oncologia | Madrid | 28041 | Spain |
| START Madrid. Centro Integral Oncologico Clara Campal; CIOCC | Madrid | 28050 | Spain |
| ID | Term |
|---|---|
| C543332 | obinutuzumab |
| C502936 | tocilizumab |
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