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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000948-14 | EudraCT Number |
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This is an open-label, multi-center, Phase Ib clinical study of cergutuzumab amunaleukin, in combination with atezolizumab, to investigate the safety, pharmacokinetics, and therapeutic activity in participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA)-positive solid tumors, whose disease has progressed on or who are intolerant to the standard of care therapy. Enrolled participants who continue treatment will be treated until loss of clinical benefit, unacceptable toxicities, or withdrawal of consent. The study will include 2 parts: a dose-escalation Part I and a dose expansion Part II. The anticipated treatment period is 24 months for both cergutuzumab amunaleukin and atezolizumab and may be modified if emerging data suggest a benefit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cergutuzumab+Atezolizumab (Part I) | Experimental | Participants will receive escalated IV doses of cergutuzumab amunaleukin in combination with atezolizumab. This is a Part I dose escalation phase of the study. Cergutuzumab amunaleukin will be escalated from a starting dose of 6 milligrams (mg) and dosing schedules of every week (qw) and every 2 weeks (q2w) may be explored. Atezolizumab will be administered in fixed flat doses of either 840 mg q2w or 1200 mg every 3 weeks (q3w). Treatment will be continued until loss of clinical benefit, unacceptable toxicities, or withdrawal of consent for a maximum treatment period of 24 months for both cergutuzumab amunaleukin and atezolizumab and may be modified if emerging data suggest longer treatment period is needed. |
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| Cergutuzumab +Atezolizumab (Part II) | Experimental | This is a Part II expansion phase of the study. Participants will receive cergutuzumab amunaleukin at maximum tolerated dose (MTD) (or recommended dose) identified during Part I in combination with atezolizumab. Treatment will be continued until loss of clinical benefit, unacceptable toxicities, or withdrawal of consent for a maximum treatment period of 24 months for both cergutuzumab amunaleukin and atezolizumab and may be modified if emerging data suggest longer treatment period is needed. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Participants will receive atezolizumab IV infusion at doses of 800 mg q2w or 1200 mg q3w. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Dose-Limiting Toxicities | Day 1 up to Day 21 | |
| MTD of Cergutuzumab Amunaleukin | Day 1 up to Day 21 | |
| Recommended Phase II Dose of Cergutuzumab Amunaleukin | Day 1 up to Day 21 | |
| Percentage of Participants with Adverse Events | Baseline up to 30 months | |
| Percentage of Participants with Infusion-Related Reactions | Baseline up to 30 months | |
| Percentage of Participants with Seroconversion of Autoantibodies | Seroconversion is defined as the presence of at least one of the following autoantibodies: anti-nuclear antibody, antidouble-stranded deoxyribose nucleic acid (DNA), cytoplasmic anti-neutrophil cytoplasmic antibody, and perinuclear anti-neutrophil cytoplasmic antibody. | Screening up to 30 months (assessed at Screening, predose [Hour 0] on Day 1 of Cycles 2, 4, and 6, and every 3 months after Cycle 6 up to approximately 30 months [cycle length= 14 or 21 days]) |
| Forced Expiratory Volume | Screening (up to 28 days prior to Cycle 1 Day 1) | |
| Forced Vital Capacity | Screening (up to 28 days prior to Cycle 1 Day 1) | |
| Percentage of Participants with Anti-Atezolizumab Antibodies |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Objective Response of Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 as Determined by the Investigator | Screening up to disease progression or death due to any cause whichever occurs first (assessed at Weeks 8 and 12, every 8 weeks thereafter for the first year, and every 12 weeks thereafter up to approximately 30 months overall) |
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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 |
|---|---|---|---|---|---|---|
| Yale Cancer Center; Medical Oncology | New Haven | Connecticut | 06520 | United States | ||
| Columbia Univ Med Ctr |
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| Cergutuzumab Amunaleukin | Drug | Participants will receive cergutuzumab amunaleukin IV infusion at escalated doses and at different dosing schedules in Part I and at MTD (or recommended dose) in Part II. |
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| Day 1 Cycle 1 up to 30 months (assessed at Day 1 of Cycles 1, 2, 3, 4, study completion/early discontinuation [up to 30 months], 28 and 120 days post last infusion up to approximately 30 months [cycle length = 14 or 21 days]) |
| Percentage of Participants with Anti-Cergutuzumab Amunaleukin Antibodies | Day 1 Cycle 1 up to 30 months (assessed at Day 1 of Cycles 1, 2, 3, 4, study completion/early discontinuation [up to 30 months], 28 and 120 days post last infusion up to approximately 30 months [cycle length = 14 or 21 days]) |
| Percentage of Participants with Disease Control (Tumor Response of CR or PR or Stable Disease [SD]) Based on RECIST v1.1 as Determined by the Investigator | Screening up to disease progression or death due to any cause whichever occurs first (assessed at Weeks 8 and 12, every 8 weeks thereafter for the first year, and every 12 weeks thereafter up to approximately 30 months overall) |
| Percentage of Participants with SD, Based on RECIST v1.1 as Determined by the Investigator | Screening up to disease progression or death due to any cause whichever occurs first (assessed at Weeks 8 and 12, every 8 weeks thereafter for the first year, and every 12 weeks thereafter up to approximately 30 months overall) |
| Progression-Free Survival Based on RECIST v1.1 as Determined by the Investigator | Screening up to disease progression or death due to any cause whichever occurs first (assessed at Weeks 8 and 12, every 8 weeks thereafter for the first year, and every 12 weeks thereafter up to approximately 30 months overall) |
| Overall Survival | Screening up to death due to any cause (up to approximately 30 months overall) |
| Area Under the Concentration Time Curve (AUC) of Cergutuzumab Amunaleukin in "Atezolizumab q2w and Cergutuzumab Amunaleukin q2w" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. Pre-infusion (PrI) (Hour 0) of PDL (PDL infusion length=60 minutes [min]), mid of infusion of CergA (CergA infusion length=360 min), end of infusion (EoI), 2, 4, 24, 72, 120 hr after CergA EoI, 169.5 hr after PDL EoI on Day 1, Cycles 1 and 4; 2, 24 hr after CergA EoI on Day 1, Cycle 2; 2 hr after CergA EoI on Day 1, Cycle 3; mid of infusion of CergA, CergA EoI, and 2 hr after CergA EoI infusion on Day 1, Cycle 5; 2, 24, 120 hr after CergA EoI on Day 1, Cycle 6; mid of infusion of CergA, CergA EoI, 2 hr after EoI of CergA on Cycle 7 Day 1 and every cycle thereafter up to study completion/early termination (up to 30 months); 28, 120 days after last infusion (up to 30 months) (cycle length = 14 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| AUC of Cergutuzumab Amunaleukin in "Atezolizumab q3w and Cergutuzumab Amunaleukin qw" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of CergA (infusion length=360 min), mid of infusion of CergA, EoI, 1.5, 4, 24, 48, 72, 96 hr after CergA EoI on Day 1, Cycles 1, 2; mid of infusion of CergA, EoI, 1.5, 2, 4, 24, 48, 72, 96 hr after CergA EoI on Days 8 and 15, Cycle 1; 2, 24 hr after CergA EoI on Day 8, Cycle 2; 2 hr after CergA EoI on Day 1, Cycle 3; mid of infusion of CergA, EoI, 2 hr after CergA EoI on Day 15, Cycle 3; 2 hr after CergA EoI on Days 1, 8 Cycle 4; mid of infusion of CergA, EoI, 2 hr after EoI of CergA on Cycle 5 Day 1 and every cycle thereafter up to study completion/early discontinuation (up to 30 months); 28, 120 days after last infusion (up to 30 months) (cycle length = 21 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Minimum Drug Concentration (Cmin) of Cergutuzumab Amunaleukin in "Atezolizumab q2w and Cergutuzumab Amunaleukin q2w" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of PDL (PDL infusion length=60 min), mid of infusion of CergA (CergA infusion length=360 min), EoI, 2, 4, 24, 72, 120 hr after CergA EoI, 169.5 hr after PDL EoI on Day 1, Cycles 1 and 4; 2, 24 hr after CergA EoI on Day 1, Cycle 2; 2 hr after CergA EoI on Day 1, Cycle 3; mid of infusion of CergA, CergA EoI, and 2 hr after CergA EoI infusion on Day 1, Cycle 5; 2, 24, 120 hr after CergA EoI on Day 1, Cycle 6; mid of infusion of CergA, CergA EoI, 2 hr after EoI of CergA on Cycle 7 Day 1 and every cycle thereafter up to study completion/early termination (up to 30 months); 28, 120 days after last infusion (up to 30 months) (cycle length = 14 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Cmin of Cergutuzumab Amunaleukin in "Atezolizumab q3w and Cergutuzumab Amunaleukin qw" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of CergA (infusion length=360 min), mid of infusion of CergA, EoI, 1.5, 4, 24, 48, 72, 96 hr after CergA EoI on Day 1, Cycles 1, 2; mid of infusion of CergA, EoI, 1.5, 2, 4, 24, 48, 72, 96 hr after CergA EoI on Days 8 and 15, Cycle 1; 2, 24 hr after CergA EoI on Day 8, Cycle 2; 2 hr after CergA EoI on Day 1, Cycle 3; mid of infusion of CergA, EoI, 2 hr after CergA EoI on Day 15, Cycle 3; 2 hr after CergA EoI on Days 1, 8 Cycle 4; mid of infusion of CergA, EoI, 2 hr after EoI of CergA on Cycle 5 Day 1 and every cycle thereafter up to study completion/early discontinuation (up to 30 months); 28, 120 days after last infusion (up to 30 months) (cycle length = 21 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Maximum Drug Concentration (Cmax) of Cergutuzumab Amunaleukin in "Atezolizumab q2w and Cergutuzumab Amunaleukin q2w" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of PDL (PDL infusion length=60 min), mid of infusion of CergA (CergA infusion length=360 min), EoI, 2, 4, 24, 72, 120 hr after CergA EoI, 169.5 hr after PDL EoI on Day 1, Cycles 1 and 4; 2, 24 hr after CergA EoI on Day 1, Cycle 2; 2 hr after CergA EoI on Day 1, Cycle 3; mid of infusion of CergA, CergA EoI, and 2 hr after CergA EoI infusion on Day 1, Cycle 5; 2, 24, 120 hr after CergA EoI on Day 1, Cycle 6; mid of infusion of CergA, CergA EoI, 2 hr after EoI of CergA on Cycle 7 Day 1 and every cycle thereafter up to study completion/early termination (up to 30 months); 28, 120 days after last infusion (up to 30 months) (cycle length = 14 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Cmax of Cergutuzumab Amunaleukin in "Atezolizumab q3w and Cergutuzumab Amunaleukin qw" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of CergA (infusion length=360 min), mid of infusion of CergA, EoI, 1.5, 4, 24, 48, 72, 96 hr after CergA EoI on Day 1, Cycles 1, 2; mid of infusion of CergA, EoI, 1.5, 2, 4, 24, 48, 72, 96 hr after CergA EoI on Days 8 and 15, Cycle 1; 2, 24 hr after CergA EoI on Day 8, Cycle 2; 2 hr after CergA EoI on Day 1, Cycle 3; mid of infusion of CergA, EoI, 2 hr after CergA EoI on Day 15, Cycle 3; 2 hr after CergA EoI on Days 1, 8 Cycle 4; mid of infusion of CergA, EoI, 2 hr after EoI of CergA on Cycle 5 Day 1 and every cycle thereafter up to study completion/early discontinuation (up to 30 months); 28, 120 days after last infusion (up to 30 months) (cycle length = 21 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Cmin of Atezolizumab in "Atezolizumab q2w and Cergutuzumab Amunaleukin q2w" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of PDL (PDL infusion length=60 min), mid of infusion of PDL, 0.5, 25.5, 121.5, 169.5, 313.5 hr after EoI of PDL on Day 1, Cycle 1; PrI (Hour 0), mid of infusion, 0.5 and 169.5 hr after PDL EoI on Day 1, Cycle 2; PrI (Hour 0) of PDL on Day 1, Cycle 3; PrI (Hour 0) of PDL, mid of infusion, 0.5, 25.5, 121.5, 169.5, 313.5 hr after PDL EoI on Day 1, Cycles 4, 6; study completion/early termination (up to 30 months), 28 and 120 days after last infusion (up to 30 months) (cycle length = 14 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Cmin of Atezolizumab in"Atezolizumab q3w and Cergutuzumab Amunaleukin qw" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of PDL (PDL infusion length=60 min), mid of infusion of PDL, 0.5, 25.5, 121.5, 169.5 hr after PDL EoI on Day 1, Cycle 1, PrI (Hour 0) of CergA, 72 hr after CergA EoI on Day 15, Cycle 1; PrI (Hour 0) of PDL, mid of infusion of PDL, 0.5, 25.5, 169.5 hr after PDL EoI on Day 1, Cycle 2; 24 hr after CergA administration on Day 9, Cycle 2; PrI (Hour 0) of CergA on Day 15, Cycle 2; PrI (Hour 0) of PDL, 72 hr after CergA EoI, 169.5 hr after PDL EoI on Day 1, Cycle 3, PrI (Hour 0) of PDL on Day 15, Cycle 3; PrI (Hour 0) of PDL, mid of infusion of PDL, 0.5, 169.5 hr after PDL EoI on Day 1, Cycle 4; study completion/early termination (up to 30 months), 28 and 120 days after last infusion (up to 30 months) (cycle length = 21 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Cmax of Atezolizumab in "Atezolizumab q2w and Cergutuzumab Amunaleukin q2w" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of PDL (PDL infusion length=60 min), mid of infusion of PDL, 0.5, 25.5, 121.5, 169.5, 313.5 hr after EoI of PDL on Day 1, Cycle 1; PrI (Hour 0), mid of infusion, 0.5 and 169.5 hr after PDL EoI on Day 1, Cycle 2; PrI (Hour 0) of PDL on Day 1, Cycle 3; PrI (Hour 0) of PDL, mid of infusion, 0.5, 25.5, 121.5, 169.5, 313.5 hr after PDL EoI on Day 1, Cycles 4, 6; study completion/early termination (up to 30 months), 28 and 120 days after last infusion (up to 30 months) (cycle length = 14 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Cmax of Atezolizumab in "Atezolizumab q3w and Cergutuzumab Amunaleukin qw" | Atezolizumab is presented as PDL and cergutuzumab amunaleukin as CergA. PrI (Hour 0) of PDL (PDL infusion length=60 min), mid of infusion of PDL, 0.5, 25.5, 121.5, 169.5 hr after PDL EoI on Day 1, Cycle 1, PrI (Hour 0) of CergA, 72 hr after CergA EoI on Day 15, Cycle 1; PrI (Hour 0) of PDL, mid of infusion of PDL, 0.5, 25.5, 169.5 hr after PDL EoI on Day 1, Cycle 2; 24 hr after CergA administration on Day 9, Cycle 2; PrI (Hour 0) of CergA on Day 15, Cycle 2; PrI (Hour 0) of PDL, 72 hr after CergA EoI, 169.5 hr after PDL EoI on Day 1, Cycle 3, PrI (Hour 0) of PDL on Day 15, Cycle 3; PrI (Hour 0) of PDL, mid of infusion of PDL, 0.5, 169.5 hr after PDL EoI on Day 1, Cycle 4; study completion/early termination (up to 30 months), 28 and 120 days after last infusion (up to 30 months) (cycle length = 21 days) | Baseline up to 30 months (detailed timeframe is provided in the outcome description) |
| Change from Baseline in Cluster of Differentiation (CD) 4 Positive (+) Type of Lymphocytes | From Baseline to 30 months |
| Change from Baseline in CD8+ Type of Lymphocytes | From Baseline to 30 months |
| Change from Baseline in Natural Killer Cells | From Baseline to 30 months |
| Change from Baseline in Monocytes | From Baseline to 30 months |
| New York |
| New York |
| 10032 |
| United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| SCRI-Tennessee Oncology | Nashville | Tennessee | 37203 | United States |
| University Health Network; Princess Margaret Hospital; Medical Oncology Dept | Toronto | Ontario | M5G 2M9 | Canada |
| Herlev Hospital; Onkologisk afdeling | Herlev | 2730 | Denmark |
| Rigshospitalet; Onkologisk Klinik | København Ø | 2100 | Denmark |
| Antoni van Leeuwenhoek Ziekenhuis | Amsterdam | 1066 CX | Netherlands |
| Erasmus MC | Rotterdam | 3015 GD | Netherlands |
| Clinica Universitaria de Navarra; Servicio de oncología | Pamplona | Navarre | 31008 | 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 |
| CHUV; Departement d'Oncologie | Lausanne | 1011 | Switzerland |
| ID | Term |
|---|---|
| C000594389 | atezolizumab |
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