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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003480-11 | EudraCT Number | ||
| RG7876 | Other Identifier | Roche |
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This open-label, two-part study is designed to assess the safety, PK, PD, and therapeutic activity of Selicrelumab in combination with vanucizumab or bevacizumab in participants with metastatic solid tumors not amenable to standard treatment. Part I (dose escalation) is designed to establish the maximum tolerated dose (MTD) of Selicrelumab in this combination. Part II (expansion) is intended to characterize the safety and tolerability of Selicrelumab in combination with bevacizumab among indication-specific cohorts and to confirm the recommended dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I: Selicrelumab, Vanucizumab/Bevacizumab | Experimental | Participants will receive a fixed dose of vanucizumab, 2 grams via IV infusion on Days 1 and 15 of every 28-day cycle. Selicrelumab will be given SC in ascending dose levels on Day 2 of Cycles 1 to 4 and every third cycle thereafter. Treatment will continue as long as the participant experiences clinical benefit or until unacceptable toxicity, withdrawal of consent, or the end of Part I of the study (expected 24 months). Due to the discontinuation of Vanucizumab development, Participants ongoing in Part I will switch from Vanucizumab to Bevacizumab. All the dose escalation has been performed using Vanucizumab. |
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| Part II: Selicrelumab, Bevacizumab | Experimental | Bevacizumab will be administered via IV infusion on days 1 and 15 of every 28-day cycle. Selicrelumab will be given SC after the Bevacizumab infusion at the dose determined in the Part I of the study on Day 2 of Cycles 1 to 4 and every third cycle thereafter. Treatment will continue as long as the participant experiences clinical benefit or until unacceptable toxicity, withdrawal of consent, or the end of Part II of the study (expected 18 months). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Selicrelumab | Drug | Selicrelumab will be provided as concentrate for solution to be administered via SC injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | From Day (D) 1 until D28 of Cycle (C)1 (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| MTD of Selicrelumab in Combination With Vanucizumab | From D1 until D28 of C1 (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Recommended Phase II Dose of Selicrelumab in Combination With Vanucizumab | From D1 until D28 of C1 (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Percentage of Participants With Adverse Events (AEs) | From D1 of C1 until treatment discontinuation and approximately 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part II: Clinical Activity of SC Selicrelumab in Combination with Bevacizumab as Assessed by Response Evaluation in Solid Tumors, Version 1.1 (RECIST v1.1) | From D1 of C1 through safety follow up visit (45 days post final dose; Cycle = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part II: Percentage of Participants With Best Overall Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Anti-Drug Antibodies (ADAs) to Selicrelumab | Predose (-1 hour [h]) on D2 of C1, C2, C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
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Inclusion Criteria:
Exclusion Criteria:
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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 | Los Angeles | California | 90048 | United States | ||
| Univ of CO Health Science Ctr |
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| Vanucizumab | Drug | Vanucizumab will be provided as solution to be administered via IV infusion. |
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| Bevacizumab | Drug | Bevacizumab will be administered via IV infusion. |
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Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) |
| Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part II: Duration of Objective Response per RECIST v1.1 Criteria | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | TBaseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part II: Percentage of Participants With Disease Control per RECIST v1.1 Criteria | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part II: Progression-free Survival (PFS) per RECIST v1.1 Criteria | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Percentage of Participants with ADAs to Vanucizumab | Predose (within 10 minutes [min] before infusion) on D1 of C1, C2, C4, and every 2 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Area Under the Concentration-Time Curve From Time 0 to Last Measureable Concentration (AUClast) of Selicrelumab Following Subcutaneous (SC) Administration | Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (up to 24 months in Part I and 18 months in Part II; cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Selicrelumab Following SC Administration | Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Maximum Concentration (Cmax) of Selicrelumab Following SC Administration | Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Time to Maximum Concentration (Tmax) of Selicrelumab Following SC Administration | Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Apparent Clearance (CL/F) of Selicrelumab Following SC Administration | Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Apparent Volume of Distribution (Vd/F) of Selicrelumab Following SC Administration | Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Apparent Terminal Half-Life (t1/2) of Selicrelumab Following SC Administration | Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: AUClast of Vanucizumab | Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: AUCinf of Vanucizumab | Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: Concentration at the End of Infusion (Cend) of Vanucizumab | Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: CL of Vanucizumab | Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: Vss of Vanucizumab | Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: t1/2 of Vanucizumab | Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: Percentage of Participants With Best Overall Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: Duration of Objective Response per RECIST v1.1 Criteria | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: Percentage of Participants With Disease Control per RECIST v1.1 Criteria | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: Progression-free Survival (PFS) per RECIST v1.1 Criteria | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Part I: Clinical Activity of SC Selicrelumab in Combination with Bevacizumab as Assessed by Response Evaluation in Solid Tumors, Version 1.1 (RECIST v1.1) | From D1 of C1 through safety follow up visit (45 days post final dose; cycle length = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Change in Blood and Tumor Tissue Immune Cell Subpopulations | Part I: C1 at D1 pre-dose Vanicizumab, D4, D9 (D15 pre and 6h post for cohorts 8 onwards); C2 at D1 and D9; C4,7,10 at D1 and D9; PD Part II: C1 D1(pre), D3,D8,D15; C2,4,7,10 D1,D8; PD | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Change in Peripheral Blood Level of Cytokines | C1D1 pre-dose Vanicizumab, C1 D2 pre-dose Selicrelumab and 3h post-dose Selicrelumab, C2D1 pre-dose Vanicizumab, C2D2 pre-dose Selicrelumab and 3h post-dose Selicrelumab, C4 D2 pre-dose Selicrelumab and 3h post-dose, PD | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Change in Blood Soluble Proteins | D1, 2, 3, 9, 15 of C1; D1, 3, 9, 15 of C2; D1 of C 4,5; D1, 15 of C7, D1 of C10, PD | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Percentage of Participants With Best overall Response Immune-Related Response Criteria (irRC) | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Duration of Objective Response per irRC | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Percentage of Participants With Disease Control per irRC | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| PFS per irRC | Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Clinical Activity of SC Selicrelumab in Combination with Bevacizumab as Assessed by Unidimensional Immune-Related Response Criteria (irRC) | From D1 of C1 through safety follow up visit (45 days post final dose; cycle length = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Overall Survival (OS) | Baseline until Participant's discontinuation or death, whichever occurs first (up to approximately 42 months) |
| Concentration at the end of Infusion (Cend) of Bevacizumab | D1 and D15 of C1, then D1 of every cycle until C7; at radiographical disease progression/tumor regression; at safety follow up visit (45 days post final dose; Cycle = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Minimum Concentration (Cmin) of Bevacizumab after Infusion | D1 and D15 of C1, then D1 of every cycle until C7; at radiographical disease progression/tumor regression; at safety follow up visit (45 days post final dose; Cycle = 28 days) | Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months) |
| Denver |
| Colorado |
| 80262 |
| United States |
| Yale Cancer Center; Medical Oncology | New Haven | Connecticut | 06520 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27514 | United States |
| Cliniques Universitaires St-Luc | Brussels | 1200 | Belgium |
| University Health Network; Princess Margaret Hospital; Medical Oncology Dept | Toronto | Ontario | M5G 2M9 | Canada |
| Rigshospitalet; Onkologisk Klinik | København Ø | 2100 | Denmark |
| Irccs Ospedale San Raffaele;Oncologia Medica | Milan | Lombardy | 20132 | Italy |
| Antoni van Leeuwenhoek Ziekenhuis | Amsterdam | 1066 CX | Netherlands |
| Erasmus Medisch Centrum | Rotterdam | 3015 GD | Netherlands |
| ICO L'Hospitalet; Servicio de oncologia medica | L'Hospitalet de Llobregat | Barcelona | 08908 | Spain |
| Hospital del Mar; Servicio de Oncologia | Barcelona | 08003 | Spain |
| Hospital Univ Vall d'Hebron; Servicio de Oncologia | Barcelona | 08035 | Spain |
| START Madrid. Centro Integral Oncologico Clara Campal; CIOCC | Madrid | 28050 | Spain |
| Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia | Valencia | 46010 | Spain |
| ID | Term |
|---|---|
| C518149 | selicrelumab |
| C000619444 | vanucizumab |
| 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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