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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04077723




Registration number
NCT04077723
Ethics application status
Date submitted
9/08/2019
Date registered
4/09/2019

Titles & IDs
Public title
A Study to Evaluate the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Englumafusp Alfa in Combination With Obinutuzumab and in Combination With Glofitamab Following a Pre-Treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Scientific title
An Open-Label, Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Englumafusp Alfa (RO7227166, A CD19 Targeted 4-1BB Ligand) in Combination With Obinutuzumab and in Combination With Glofitamab Following a Pre-treatment Dose of Obinutuzumab Administered in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Secondary ID [1] 0 0
2019-000416-28
Secondary ID [2] 0 0
BP41072
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Non-Hodgkin 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Englumafusp alfa
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Glofitamab
Treatment: Drugs - Tocilizumab

Experimental: Part I - Combination Dose-Escalation: Mixed r/r NHL participants will receive a fixed dose of obinutuzumab up to seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab in a three-weekly schedule (Q3W).

Experimental: Part II - Combination Dose-Escalation: Mixed r/r participants and participants with mixed r/r mantle cell lymphoma (MCL) and Richters transformation will receive a fixed dose of obinutuzumab seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).

Experimental: Part III - Dose-Expansion Stage: Participants with r/r diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS), high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), and DLBCL arising from FL (transformed FL) will receive englumafusp alfa administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).


Treatment: Drugs: Englumafusp alfa
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).

Treatment: Drugs: Obinutuzumab
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).

Treatment: Drugs: Glofitamab
A fixed dose of glofitamab will be administered Q3W in combination with englumafusp alfa in Part II and Part III

Treatment: Drugs: Tocilizumab
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Nature and frequency of dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
28 days in Part I and Part II
Primary outcome [2] 0 0
Proportion of Participants with Adverse Event (AE)
Timepoint [2] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Primary outcome [3] 0 0
Overall Response Rate (ORR)
Timepoint [3] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Primary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Primary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
After end of Study approximately every 3 months until death, loss to follow-up or study termination
Primary outcome [6] 0 0
Progression-free Survival (PFS)
Timepoint [6] 0 0
After end of Study approximately every 3 months until death, loss to follow-up or study termination
Primary outcome [7] 0 0
Overall Survival (OS)
Timepoint [7] 0 0
After end of Study approximately every 3 months until death, loss to follow-up or study termination
Primary outcome [8] 0 0
Complete Response (CR)
Timepoint [8] 0 0
Part III: Up to 9 months or up to 18 months
Secondary outcome [1] 0 0
Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with obinutuzumab and glofitamab
Timepoint [1] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [2] 0 0
Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with obinutuzumab and glofitamab
Timepoint [2] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [3] 0 0
Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with obinutuzumab and glofitamab
Timepoint [3] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [4] 0 0
Clearance (CL) of englumafusp alfa in combination with obinutuzumab and glofitamab
Timepoint [4] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [5] 0 0
Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with obinutuzumab and glofitamab
Timepoint [5] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [6] 0 0
ORR
Timepoint [6] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [7] 0 0
DCR
Timepoint [7] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [8] 0 0
DOR
Timepoint [8] 0 0
After end of Study approximately every 3 months until death, loss to follow-up or study termination
Secondary outcome [9] 0 0
PFS
Timepoint [9] 0 0
After end of Study approximately every 3 months until death, loss to follow-up or study termination
Secondary outcome [10] 0 0
OS
Timepoint [10] 0 0
After end of Study approximately every 3 months until death, loss to follow-up or study termination
Secondary outcome [11] 0 0
Proportion of Participants with Adverse Event (AE)
Timepoint [11] 0 0
After end of Study approximately every 3 months until death, loss to follow-up or study termination
Secondary outcome [12] 0 0
Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with glofitamab
Timepoint [12] 0 0
Part III: Up to 9 months or up to 18 months
Secondary outcome [13] 0 0
Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with glofitamab
Timepoint [13] 0 0
Part III: Up to 9 months or up to 18 months
Secondary outcome [14] 0 0
Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with glofitamab
Timepoint [14] 0 0
Part III: Up to 9 months or up to 18 months
Secondary outcome [15] 0 0
Clearance (CL) of englumafusp alfa in combination with glofitamab
Timepoint [15] 0 0
Part III: Up to 9 months or up to 18 months
Secondary outcome [16] 0 0
Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with glofitamab Part I/II/III
Timepoint [16] 0 0
Part III: Up to 9 months or up to 18 months
Secondary outcome [17] 0 0
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
Timepoint [17] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [18] 0 0
B-cell reduction in blood and tumor tissue
Timepoint [18] 0 0
Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Secondary outcome [19] 0 0
Change from Baseline in englumafusp alfa Anti-Drug Antibody (ADA) Titer
Timepoint [19] 0 0
Part 1: Up to 24 months; Part ll/lll: Up to 18 months
Secondary outcome [20] 0 0
Time to First Complete Response (TFCR)
Timepoint [20] 0 0
Up to 18 months
Secondary outcome [21] 0 0
Time to First Overall Response (TFOR)
Timepoint [21] 0 0
Up to 18 months
Secondary outcome [22] 0 0
Duration of Complete Response (DOCR)
Timepoint [22] 0 0
Part III: Up to 9 months or up to 18 months
Secondary outcome [23] 0 0
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)
Timepoint [23] 0 0
Part III: Up to 9 months or up to 18 months
Secondary outcome [24] 0 0
Change from Baseline in Physical Function, Role Function, and HRQoL According to the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Scale
Timepoint [24] 0 0
Part III: Up to 9 months or up to 18 months

Eligibility
Key inclusion criteria
* History or status of a histologically-confirmed hematological malignancy that is expected to express CD19 and CD20; relapse after or failure to respond to at least one prior treatment regimen; no available treatment options that are expected to prolong survival (Part I and II); relapsed after or failed to respond to only one prior systemic treatment regimen (Part III)
* Must have at least one measurable target lesion (>/= 1.5 cm) in its largest dimension by computed tomography scan
* Able and willing to provide a fresh biopsy from a safely accessible site, per Investigator's determination, providing the participant has more than one measurable target lesion
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or </= 2 for some participants in Part III
* Life expectancy of >/= 12 weeks
* Adverse events from prior anti-cancer therapy must have resolved to Grade </= 1
* Adequate liver, hematological, and renal function
* Negative test results for acute or chronic hepatitis B virus infection
* Negative test results for hepatitis C virus and HIV
* The contraception and abstinence requirements are intended to prevent exposure of an embryo to the study treatment. The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure
* Female participants: A female participant is eligible to participate if she is not pregnant and not breastfeeding, and if at least one of the following applies: women of non-childbearing potential (WONCBP); women of child bearing potential (WOCBP) who agree to remain abstinent or use two highly effective contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 18 months after obinutuzumab or 3.5 months after the last dose of englumafusp alfa, 2 months after last dose of glofitamab, or 3 months after the last dose of tocilizumab, whichever is longer. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal occlusion/ ligation, male sexual partner who is sterilized, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method; have a negative pregnancy test (blood) within the 7 days prior to the first study treatment administration
* Male participants: During the treatment period and for at least 3 months after obinutuzumab, or 3.5 months after the last dose of englumafusp alfa, 2 months after the last dose of glofitamab, or 2 months after the last dose of tocilizumab whichever is longer, agreement to: Remain abstinent or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year, with a partner who is a women of childbearing potential. With pregnant female partner, remain abstinent or use contraceptive measures such as a condom to avoid exposing the embryo; refrain from donating sperm during this same period
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count (ALC) or the presence of abnormal cells in the peripheral blood signifying circulating lymphoma cells (for some participants in Part III, ALC only)
* Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
* Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics
* Pregnant or breast-feeding or intending to become pregnant during the study
* Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines or monoclonal antibodies within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion
* History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents and auto-immune disease
* Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational or approved anti-cancer agent within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to obinutuzumab infusion
* Prior solid organ transplantation
* Prior allogeneic stem cell transplant (SCT) and prior chimeric antigen receptor -T-cell therapy
* Autologous SCT within 100 days prior to obinutuzumab infusion
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and confirmed progressive multifocal leukoencephalopathy
* Current or past history of central nervous system (CNS) lymphoma and CNS disease
* Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
* Major surgery or significant traumatic injury < 28 days prior to the Gpt infusion or anticipation of the need for major surgery during study treatment
* Participants with another invasive malignancy in the last 2 years
* Significant cardiovascular disease
* Administration of a live, attenuated vaccine within 4 weeks before Gpt infusion or anticipation that such a live attenuated vaccine will be required during the study
* Received systemic immunosuppressive medications (including but not limited to cyclohosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to Gpt, with the exception of corticosteroid treatment <=25 mg/day of prednisone or equivalent, however there must be documentation that the participant was on a stable dose of at least a 2-week duration prior to Gpt infusion. Inhaled and topical steroids are permitted

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2027
Actual
Sample size
Target
498
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Gent
Country [6] 0 0
Denmark
State/province [6] 0 0
København Ø
Country [7] 0 0
France
State/province [7] 0 0
Lille
Country [8] 0 0
France
State/province [8] 0 0
Montpellier
Country [9] 0 0
France
State/province [9] 0 0
Pierre Benite
Country [10] 0 0
France
State/province [10] 0 0
Rennes
Country [11] 0 0
Italy
State/province [11] 0 0
Lombardia
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Leicester
Country [14] 0 0
United Kingdom
State/province [14] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BP41072 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04077723