This is a phase I/II, open-label, dose-escalation study designed to evaluate the safety, tolerability, and efficacy of englumafusp alfa (RO7227166) in participants with relapsed/refractory Non-Hodgkin's Lymphoma (r/r NHL). Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab and in combination with glofitamab. A fixed dose of obinutuzumab (Gpt; pre-treatment) will be administered up to seven days prior to the first administration of englumafusp alfa and seven days prior to the first administration of glofitamab. This entry-into-human study is divided into a dose-escalation stage (Part I and Part II) and a dose expansion stage (Part III).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
498
Englumafusp alfa will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III).
A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa, then in combination with obinutuzumab Q3W (Part I). A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa or between Day -3 and -7 (Part II and Part III).
A fixed dose of glofitamab will be administered Q3W in combination with englumafusp alfa in Part II and Part III
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
City of Hope Medical Center
Pasadena, California, United States
ACTIVE_NOT_RECRUITINGUniversity of California San Francisco
San Francisco, California, United States
RECRUITINGColorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
Denver, Colorado, United States
RECRUITINGBeth Israel Medical Center
Boston, Massachusetts, United States
RECRUITINGWashington University School of Medicine
St Louis, Missouri, United States
RECRUITINGMSKCC
New York, New York, United States
RECRUITINGOhioHealth Research Institute
Columbus, Ohio, United States
RECRUITINGSCRI Oncology Partners
Nashville, Tennessee, United States
RECRUITINGSouth Austin Medical Center
Austin, Texas, United States
RECRUITINGThe University of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITING...and 33 more locations
Nature and frequency of dose-limiting toxicities (DLTs)
Time frame: 28 days in Part I and Part II
Proportion of Participants with Adverse Event (AE)
Incidence, nature, and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Overall Response Rate (ORR)
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Disease Control Rate (DCR)
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Duration of Response (DOR)
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Progression-free Survival (PFS)
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Overall Survival (OS)
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Complete Response (CR)
Time frame: Part III: Up to 9 months or up to 18 months
Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Clearance (CL) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
ORR
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
DCR
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
DOR
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
PFS
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
OS
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Proportion of Participants with Adverse Event (AE)
Incidence, nature, and severity of AEs graded according to the NCI CTCAE v5.0
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with glofitamab
Time frame: Part III: Up to 9 months or up to 18 months
Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with glofitamab
Time frame: Part III: Up to 9 months or up to 18 months
Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with glofitamab
Time frame: Part III: Up to 9 months or up to 18 months
Clearance (CL) of englumafusp alfa in combination with glofitamab
Time frame: Part III: Up to 9 months or up to 18 months
Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with glofitamab Part I/II/III
Time frame: Part III: Up to 9 months or up to 18 months
T-cell and Natural killer (NK)-cell status in blood, using markers of T and NK-cell lineage, function and activation including, but not limited to, CD3, CD8, 41BB, and Ki67 expression
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
B-cell reduction in blood and tumor tissue
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Change from Baseline in englumafusp alfa Anti-Drug Antibody (ADA) Titer
Time frame: Part 1: Up to 24 months; Part ll/lll: Up to 18 months
Time to First Complete Response (TFCR)
Time frame: Up to 18 months
Time to First Overall Response (TFOR)
Time frame: Up to 18 months
Duration of Complete Response (DOCR)
Time frame: Part III: Up to 9 months or up to 18 months
Change from Baseline in Physical Function, Role Function, and Health-Related Quality of Life (HRQoL) Based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Time frame: Part III: Up to 9 months or up to 18 months
Change from Baseline in Physical Function, Role Function, and HRQoL According to the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Scale
Time frame: Part III: Up to 9 months or up to 18 months
Reference Study ID Number: BP41072 https://forpatients.roche.com/
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