Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma (ELEVATE HNSCC)
Head and Neck Squamous Cell Carcinoma
About this trial
This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma
Eligibility Criteria
Key Inclusion Criteria:
- Histologically or cytologically confirmed metastatic or locally recurrent HNSCC that is considered incurable by local therapies
Safety Run-in Cohort 1 and Phase 2 Cohorts 1
- Should not have had prior systemic therapy administered in the recurrent or metastatic setting.
- Eligible primary tumor locations include oropharynx, oral cavity, hypopharynx, and larynx. Nasopharynx is not included.
- HNSCC per protocol specified inclusion criteria regardless of PD-L1 status
Safety Run-in Cohort 2 and Phase 2 Cohort 3
- Histologically or cytologically confirmed locally advanced/mHNSCC regardless of PD-L1 status with at least 1 and no more than 2 lines of prior systemic anticancer therapy in the locally advanced/metastatic setting
Key Exclusion Criteria:
- Active central nervous system (CNS) disease (individuals with asymptomatic and stable, treated CNS lesions who have been off corticosteroids, radiation, or other CNS-directed therapy for at least 4 weeks are not considered active)
- History of (noninfectious) pneumonitis that required steroids or current pneumonitis
Safety Run-in Cohort 1, Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab (if Applicable), and Phase 2 Cohorts 1 and 2
Prior treatment with any of the following:
- Anti-programmed cell death protein 1 or anti-PD-L1 checkpoint inhibitors
- Anti-cytotoxic T-lymphocyte-associated protein 4 checkpoint inhibitors
Safety Run-in Cohort 2 and Phase 2 Cohort 3
- Progressive disease within 6 months of completion of curatively intended systemic treatment for locally advanced/mHNSCC
- Prior treatment with a taxane
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Ironwood Cancer and Research CenterRecruiting
- City of HopeRecruiting
- UCLA Hematology/OncologyRecruiting
- Stanford Cancer InstituteRecruiting
- Torrance Memorial Physician Network - Cancer Care AssociatesRecruiting
- Providence Medical FoundationRecruiting
- Ocala Oncology CenterRecruiting
- University Center and Blood Center,LLC.Recruiting
- Indiana University Melvin and Bren Simon Cancer CenterRecruiting
- Virginia Piper Cancer Center (Alliant HealthRecruiting
- Washington University of Medicine- Siteman Cancer CenterRecruiting
- Astera Cancer CareRecruiting
- Icahn School of Medicine at Mount Sinai and the Mount Sinai Hospital
- New York Cancer and Blood SpecialistsRecruiting
- Sanford Roger Maris Cancer CenterRecruiting
- OU Health Stephenson Cancer CenterRecruiting
- Oregon Health and Science University
- Lancaster General HospitalRecruiting
- Medical University of South CarolinaRecruiting
- Avera Cancer InstituteRecruiting
- MD Anderson Cancer CenterRecruiting
- Huntsman Cancer InstituteRecruiting
- St. Vincent's Hospital SydneyRecruiting
- Macquarie UniversityRecruiting
- Blacktown HospitalRecruiting
- Cairns HospitalRecruiting
- University of the Sunshine CoastRecruiting
- Princess Alexandra HospitalRecruiting
- Austin HealthRecruiting
- Alfred HealthRecruiting
- ZiekenhuisNetwerk Antwerpen (ZNA) - StuivenbergRecruiting
- Algemeen Ziekenhuis KlinaRecruiting
- UZ AntwerpenRecruiting
- Universitaire Ziekenhuis LeuvenRecruiting
- Centre Hospitalizer De L'ArdenneRecruiting
- AZ Sint-MaartenRecruiting
- CHU UCL Namur - Sainte-ElisabethRecruiting
- Institut BergonieRecruiting
- Centre Georges François LeclercRecruiting
- Centre Léon BérardRecruiting
- Hopital de la TimoneRecruiting
- Centre de Lutte Contre le Cancer (CLCC) - Centre Antoine Lacassagne (CAL) - Site EstRecruiting
- Institut CurieRecruiting
- Hopital Pitie-SalpetriereRecruiting
- Civils de Lyon-Centre Hopitalier Lyon SudRecruiting
- Hopital FochRecruiting
- Institut Gustave RoussyRecruiting
- Charite University MedicineRecruiting
- Universitatsmedizin GottingenRecruiting
- Kath. Marienkrankenhaus gGmbHRecruiting
- Universitäres Krebszentrum LeipzigRecruiting
- Technische Universitat Munchen (TUM) - Klinikum Rechts der IsarRecruiting
- Hong Kong United Oncology Centre
- Queen Mary HospitalRecruiting
- Princess Margaret HospitalRecruiting
- Hong Kong Sanatorium and Hospital
- Azienda Ospedaliero - Universitaria di Bologna - IRCCSRecruiting
- ASST degli Spedali Civili di BresciaRecruiting
- Azienda Ospedaliera Spedali Civili di BresciaRecruiting
- Ospedale San Luca LucaRecruiting
- Fondazione IRCCS Istituto Nazionale Tumori MilanoRecruiting
- Arcispedale Santa Maria NuovaRecruiting
- Azienda Ospedaliero - Universitaria SeneseRecruiting
- Centrum Onkologii im. Prof. Franciszka Lukaszczyka w BydgoszczyRecruiting
- Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie, Panstwowy Instytut Badawczy, Oddzial x GliwicachRecruiting
- Wielkopolskie Centrum Onkologii im. Marii Sklodowskiej-Curie, Oddzial Onkologii Klinicznej i Immunookologii z Poddoddzialem Dziennym i Izba PrzyjecRecruiting
- Wojewodzki Szpital Specjalistyczny w SiedlcachRecruiting
- Narodowy Instytut Onkologii im. M. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Glowy i SzyiRecruiting
- Hospital de BragaRecruiting
- Centro Hospitalar do AlgarveRecruiting
- Hospital CUF DescobertasRecruiting
- Unidade Local de Saude de Matosinhos EPE - Hospital Pedro Hispano SARecruiting
- Centro Hospitalar Universitario do PortoRecruiting
- Instituto Portugues de Oncologia Do Porto Francisco Gentil,E.P.E.Recruiting
- Hospital Universitari Vall d'HebronRecruiting
- Hospital del MarRecruiting
- Hospital De La Santa Creu I Sant PauRecruiting
- Hospital Universitario de JaenRecruiting
- Hospital General Universitario Gregorio MaranonRecruiting
- MD Anderson Cancer CenterRecruiting
- Hospital Universitario La PazRecruiting
- Hospital Regional Universitario de MalagaRecruiting
- Clinica Universidad de NavarraRecruiting
- Hospital Universitario Virgen MacarenaRecruiting
- Hospital Universitario Virgen del RocioRecruiting
- Hospital Universitari i Politecnic La FeRecruiting
- Hospital Clínico Universitario de ValenciaRecruiting
- Royal Marsden NHS Foundation Trust, Royal Marsden - SuttonRecruiting
- Musgrove Park HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Active Comparator
Experimental
Experimental
Experimental
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Safety Run-in Cohort 2, Magrolimab + Docetaxel
Pre-expansion Safety Run-in Cohort, Magrolimab + Pembrolizumab
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)
Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)
Phase 2 Cohort 2, Magrolimab + Pembrolizumab
Phase 2 Cohort 3, Magrolimab + Docetaxel
Participants with untreated metastatic or unresectable, locally recurrent head and neck squamous cell carcinoma (HNSCC) regardless of programmed cell death ligand 1 (PD-L1) status will receive the following: magrolimab pembrolizumab 200 mg on Day 1 of each cycle 5-fluorouracil (5-FU) 1000 mg/m^2/day Days 1-4 of each cycle (for up to 6 cycles) platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin area under the concentration versus time curve (AUC) 5 per investigator choice (for up to 6 cycles)) Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the recommended Phase 2 dose (RP2D) is determined. Each cycle is 21 days.
Participants with locally advanced/metastatic HNSCC regardless of PD-L1 status who were previously treated with at least 1 and no more than 2 lines of prior systemic therapy will receive the following: magrolimab docetaxel 75 mg/m^2 on Day 1 of each cycle Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the RP2D is determined. Each cycle is 21 days.
The pre-expansion safety run-in cohort may be conducted at the sponsor's discretion prior to the initiation of Phase 2 Cohort 2. Participants with untreated metastatic or unresectable, locally recurrent HNSCC with a PD-L1 combined positive score (CPS) ≥ 1 will receive magrolimab and pembrolizumab 200 mg on Day 1 of each cycle. Each cycle is 21 days. Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the RP2D is determined. Each cycle is 21 days.
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, zimberelimab 360 mg on Day 1 of each cycle, 5-FU 1000 mg/m^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Zimberelimab therapy will be administered until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
Participants with untreated metastatic or unresectable, locally recurrent HNSCC with a PD-L1 combined positive score (CPS) ≥ 1 will receive magrolimab at the RP2D determined in the Safety run-in cohort 1 and pembrolizumab 200 mg on Day 1 of each cycle. Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
Participants with locally advanced/metastatic HNSCC regardless of PD-L1 status who were previously treated with at least 1 and no more than 2 lines of prior systemic therapy will receive magrolimab at the RP2D determined in the Safety run-in cohort 2 and docetaxel 75 mg/m^2 on Day 1 of each cycle. Each cycle is 21 days. Magrolimab and docetaxel will be continued until loss of clinical benefit, unacceptable toxicity, or death.