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| ID | Type | Description | Link |
|---|---|---|---|
| Z0011001 | Other Identifier | Pfizer |
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Study terminated due to change in therapeutic landscape.
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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
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The purpose of this study is to evaluate the safety, tolerability, and potential clinical benefits of ZN-c3 administered in combination with encorafenib and cetuximab in adult participants with metastatic BRAF V600E mutant colorectal cancer previously treated with one or two treatment regimens.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation | Experimental | Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab |
|
| Dose Expansion | Experimental | Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZN-c3 | Drug | ZN-c3 tablet by mouth, in combination with encorafenib |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs) | DLTs defined as treatment-related AEs occurring within the first 29 days after the start of any study treatment that in the opinion of the investigator cannot be reasonably attributed to the participant's underlying disease, concomitant medications, or pre-existing conditions. | From Lead-in Day -1 to Cycle 1 Day 28 |
| Dose Expansion Phase - Objective response rate (ORR) | ORR defined as the proportion of participants who achieves a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator per RECIST Version 1.1. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation Phase - Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 | Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results. | From first dose of any study intervention through 28 days after the last dose of any study intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USC Norris Comprehensive Cancer Center | Los Angeles | California | 90033 | United States | ||
| Alliance for Multispecialty Research, LLC |
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| Encorafenib | Drug | Encorafenib capsule by mouth, in combination with ZN-c3 |
|
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| Cetuximab | Drug | Infusion |
|
|
| Proportion of participants with dose interruptions due to AEs in Dose Escalation Phase | From first dose of any study intervention through 28 days after the last dose of any study intervention |
| Proportion of participants with dose modifications due to AEs in Dose Escalation Phase | From first dose of any study intervention through 28 days after the last dose of any study intervention |
| Proportion of participants with discontinuations due to AEs in Dose Escalation Phase | From first dose of any study intervention through 28 days after the last dose of any study intervention |
| Dose Escalation Phase - Objective response rate (ORR) | ORR defined as the proportion of participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST Version 1.1. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Escalation Phase - Duration of Response (DOR) | DOR defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented disease progression per RECIST version 1.1, or death due to any cause. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Escalation Phase - Progression Free Survival (PFS) | PFS defined as the time from the first dose to the earliest documented disease progression per RECIST version 1.1, or death due to any cause. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Escalation Phase - Disease Control Rate (DCR) | DCR defined as the proportion of participants with BOR of CR, PR, or stable disease (SD), per RECIST version 1.1. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Escalation Phase - Time to Response (TTR) | TTR defined as the time from first dose to first radiographic evidence of response (CR or PR) per RECIST version 1.1. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Escalation - ZN-c3 plasma exposure: AUC | From lead in day -1 visit through Cycle 1 Day 15 |
| Dose Escalation - ZN-c3 plasma exposure: Cmax | From lead in day -1 visit through Cycle 1 Day 15 |
| Dose Escalation - ZN-c3 plasma exposure: Tmax | From lead in day -1 visit through Cycle 1 Day 15 |
| Dose Escalation - Encorafenib plasma exposure: AUC | From lead in day -1 visit through Cycle 1 Day 15 |
| Dose Escalation - Encorafenib plasma exposure: Cmax | From lead in day -1 visit through Cycle 1 Day 15 |
| Dose Escalation - Encorafenib plasma exposure: Tmax | From lead in day -1 visit through Cycle 1 Day 15 |
| Dose Expansion Phase - Duration of Response (DOR) | DOR defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented disease progression per RECIST version 1.1, or death due to any cause. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Expansion Phase - Progression Free Survival (PFS) | PFS defined as the time from the first dose to the earliest documented disease progression per RECIST version 1.1, or death due to any cause. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Expansion Phase - Disease Control Rate (DCR) | DCR defined as the proportion of participants with BOR of CR, PR, or stable disease (SD), per RECIST version 1.1. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Expansion Phase - Time to Response (TTR) | TTR defined as the time from first dose to first radiographic evidence of response (CR or PR) per RECIST version 1.1. | From first dose of any study intervention every 8 weeks during treatment, up to 12 months |
| Dose Expansion Phase - Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 | Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results. | From first dose of any study intervention through 28 days after the last dose of any study intervention |
| Proportion of participants with dose interruptions due to AEs in Dose Expansion Phase | From first dose of any study intervention through 28 days after the last dose of any study intervention |
| Proportion of participants with dose modifications due to AEs in Dose Expansion Phase | From first dose of any study intervention through 28 days after the last dose of any study intervention |
| Proportion of participants with discontinuations due to AEs in Dose Expansion Phase | From first dose of any study intervention through 28 days after the last dose of any study intervention |
| Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC | Lead in day 7 |
| Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax | Lead in day 7 |
| Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax | Day 7 |
| Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC | Cycle 1 Day 15 |
| Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax | Cycle 1 Day 15 |
| Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax | Cycle 1 Day 15 |
| Dose Expansion - ZN-c3 plasma exposure: AUC | Cycle 1 Day 15 |
| Dose Expansion - ZN-c3 plasma exposure: Cmax | Cycle 1 Day 15 |
| Tumor tissue BRAF V600E mutational status | From lead in day 1 visit through the last dose of any study intervention, up to 12 months |
| Merriam |
| Kansas |
| 66204 |
| United States |
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| The Queen Elizabeth Hospital | Woodville South | South Australia | 5011 | Australia |
| Peter MacCallum Cancer Centre | Melbourne | Victoria | 3000 | Australia |
| Hämatologie- Onkologie im Zentrum MVZ GmbH | Augsburg | Bavaria | 86150 | Germany |
| Klinikum der Universität München Großhadern | Munich | Bavaria | 81377 | Germany |
| Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie | Munich | Bavaria | 81737 | Germany |
| Institut für Klinisch Onkologische Forschung | Frankfurt am Main | Hesse | 60488 | Germany |
| DRK Kliniken Berlin - Köpenick | Berlin | State of Berlin | 12559 | Germany |
| Semmelweis University-Department of Internal Medicine and Oncology | Budapest | Budapest | 1083 | Hungary |
| Clinexpert Kft. Bugat Pal Korhaz | Gyöngyös | 3200 | Hungary |
| Istituto Nazionale Tumori IRCCS Fondazione Pascale | Naples | Campania | 80131 | Italy |
| IRCCS Casa Sollievo della Sofferenza | San Giovanni Rotondo | Foggia | 71013 | Italy |
| Istituto Europeo di Oncologia | Milan | Milano | 20141 | Italy |
| ASST Grande Ospedale Metropolitano Niguarda | Milan | Milano | 20162 | Italy |
| AOUI Verona | Verona | Veneto | 37126 | Italy |
| Szpital Uniwersytecki w Krakowie | Krakow | Lesser Poland Voivodeship | 31-501 | Poland |
| Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie | Krakow | Lesser Poland Voivodeship | 31-826 | Poland |
| Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie | Warsaw | Masovian Voivodeship | 02-034 | Poland |
| Opolskie Centrum Onkologii w Opolu im. prof. Tadeusza Koszarowskiego | Opole | Opole Voivodeship | 45-061 | Poland |
| Hospital Universitari Vall d'Hebron | Barcelona | Barcelona | 08035 | Spain |
| Parc de Salut Mar - Hospital del Mar | Barcelona | Catalonia | 08003 | Spain |
| Hospital Universitario Reina Sofia | Córdoba | Cordoba | 14004 | Spain |
| Hospital Universitario La Paz | Madrid | Madrid | 28046 | Spain |
| Hospital Universitario Puerta de Hierro Majadahonda | Madrid | Madrid | 28222 | Spain |
| Fundación Instituto Valenciano de Oncología | Valencia | Valenciana, Comunitat | 46009 | Spain |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| C000601108 | encorafenib |
| D000068818 | Cetuximab |
| 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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