Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03467373




Registration number
NCT03467373
Ethics application status
Date submitted
9/03/2018
Date registered
16/03/2018
Date last updated
26/04/2024

Titles & IDs
Public title
A Study of Glofitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (CHP) in Participants With Non-Hodgkin Lymphomas or With DLBCL
Scientific title
A Phase Ib Study Evaluating Glofitamab (RO7082859) in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin (POLA) Plus Rituximab (R), Cyclophosphamide, Doxorubicin, and Prednisone (CHP) in Participants With Relapsed or Refractory Non-Hodgkin Lymphoma (R/R NHL) or in Participants With Untreated Diffuse Large B-Cell Lymphoma (DLBCL)
Secondary ID [1] 0 0
2017-003648-18
Secondary ID [2] 0 0
NP40126
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-Cell Lymphoma 0 0
Non-Hodgkin Lymphoma 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 - Glofitamab
Treatment: Drugs - Obinutuzumab (G)
Treatment: Drugs - Rituximab (R)
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisone
Treatment: Drugs - Polatuzumab vedotin

Experimental: Part 1: Dose Escalation r/r NHL - Dose finding in participants with r/r NHL: the study will explore different doses of glofitamab in the induction period, starting at a dose of 70 mcg administered in combination with standard of care doses of G/R CHOP and R-CHOP every 3 weeks (Q3W). Participants with r/r NHL will receive 6 cycles of induction treatment (G/R-CHOP). Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOInd) may optionally receive post-induction treatment (referred to as maintenance) with glofitamab alone.
The use of G versus R in Cycle 1 will be compared in parallel dose escalation cohorts.

Experimental: Part 2: DLBCL G/R-CHOP - Participants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by G/R-CHOP + glofitamab for subsequent cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6 (up to 8). The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.

Experimental: Part 2: DLBCL Pola-R-CHP - Participants with untreated DLBCL will receive Pola-R-CHP + glofitamab on Day 1 of each 21-day cycle for a maximum of 6 cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.


Treatment: Drugs: Glofitamab
Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.

Treatment: Drugs: Obinutuzumab (G)
Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only

Treatment: Drugs: Rituximab (R)
Rituximab will be administered as an IV infusion at a dose of 375 mg/m^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).

Treatment: Drugs: Tocilizumab
Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide 750 mg/m^2 administered IV on Day 1 of each 21-day cycle

Treatment: Drugs: Doxorubicin
Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle

Treatment: Drugs: Vincristine
Vincristine 1.4 mg/m^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg

Treatment: Drugs: Prednisone
Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Treatment: Drugs: Polatuzumab vedotin
Polatuzumab vedotin 1.8 mg/kg administered IV on Day 1 of each 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 29 months
Primary outcome [2] 0 0
Part I and II: Percentage of Participants with Adverse Events
Timepoint [2] 0 0
Up to 29 months
Secondary outcome [1] 0 0
Parts I and II: Percentage of Participants with a Complete Response (CR) as Assessed by the Investigator using Modified Lugano 2014 Criteria
Timepoint [1] 0 0
Up to 29 months
Secondary outcome [2] 0 0
Parts I and II: Percentage of Participants with Overall Response (Partial Response [PR] or Complete Response [CR])
Timepoint [2] 0 0
Up to 29 months
Secondary outcome [3] 0 0
Parts I and II: Duration of Response (DOR)
Timepoint [3] 0 0
Up to 29 months
Secondary outcome [4] 0 0
Duration of CR
Timepoint [4] 0 0
Up to 29 months
Secondary outcome [5] 0 0
Progression-Free Survival (PFS)
Timepoint [5] 0 0
Up to 29 months
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
Up to 29 months
Secondary outcome [7] 0 0
Time to First Complete Response (TFCR)
Timepoint [7] 0 0
Up to 29 months
Secondary outcome [8] 0 0
Time to First Response (TFOR)
Timepoint [8] 0 0
Up to 29 months
Secondary outcome [9] 0 0
Parts I and II: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab
Timepoint [9] 0 0
Cycle 1 Day 1 up to 29 months
Secondary outcome [10] 0 0
Parts I and II: Time to Maximum Serum Concentration (tmax) of Glofitamab
Timepoint [10] 0 0
Cycle 1 Day 1 up to 29 months
Secondary outcome [11] 0 0
Parts I and II: Maximum Serum Concentration (Cmax) of Glofitamab
Timepoint [11] 0 0
Cycle 1 Day 1 up to 29 months
Secondary outcome [12] 0 0
Parts I and II: Minimum Serum Concentration (Cmin) of Glofitamab
Timepoint [12] 0 0
Cycle 1 Day 1 up to 29 months
Secondary outcome [13] 0 0
Change from Baseline in T-cell Activation Markers
Timepoint [13] 0 0
Up to 29 months

Eligibility
Key inclusion criteria
- Age >/=18 years

- For Part I r/r NHL dose-escalation, and Part II r/r NHL expansion:
Histologically-confirmed NHL that is expected to express CD20, and which has
relapsed/progressed following at least one prior treatment regimen containing R or G.
Participants must be appropriate for treatment with CHOP and typically should not have
been exposed to prior anthracyclines or must not exceed the cumulative lifetime dose
of anthracyclines

- For Part II untreated DLBCL expansion: Histologically confirmed previously-untreated
DLBCL that is expected to express CD20

- Able to provide a pretreatment biopsy between the final dose of last prior therapy and
initiation of study medication at Cycle 1/Day 1

- Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion,
defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally
measurable extranodal lesion, defined as >1.0 cm in its longest dimension.

- Participants must have at least one measurable target lesion (> or = 1.5 cm) in its
largest dimension by computed tomography (CT) scan

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for
participants with r/r NHL; ECOG performance status 0-3 for participants with untreated
DLBCL

- Life expectancy (in the opinion of the Investigator) of 18 weeks

- Adverse events (AEs) from prior anti-cancer therapy must have resolved to Grade </= 1

- Adequate liver function

- Adequate hematological function

- Adequate renal function

- Negative serologic or polymerase chain reaction (PCR) test results for acute or
chronic hepatitis B virus (HBV) infection

- Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus
(HIV)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Inability to comply with protocol mandated hospitalization and restrictions

- Participants with known active infection, or reactivation of a latent infection,
whether bacterial, viral (including, but not limited to Epstein Barr virus (EBV),
cytomegalovirus (CMV), HBV, HCV, and HIV), fungal, mycobacterial, or other pathogens
(excluding fungal infections of nail beds) or any major episode of infection requiring
hospitalization or treatment with IV antibiotics (for IV antibiotics, this pertains to
completion of last course of antibiotic treatment) within 4 weeks of dosing

- Prior treatment with systemic immunotherapeutic agents, including, but not limited to,
radioimmuno-conjugates, antibody-drug conjugates, immune/cytokines, and monoclonal
antibodies (e.g., anti-CTLA4, anti-PD1, and anti-PDL1) within 4 weeks or five
half-lives of the drug, whichever is shorter, before G- or R-CHOP or Pola-R-CHP
infusion on Cycle 1/Day 1

- Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form
of Charcot-Marie-Tooth disease (only for participants treated in the polatuzumab
vedotin arm)

- History of treatment-emergent immune-related AEs associated with prior
immunotherapeutic agents, as follows: Grade >/=3 AEs, with the exception of Grade 3
endocrinopathy managed with replacement therapy; Grade 1-2 AEs that did not resolve to
baseline after treatment completion

- Contraindication to any of the individual components of the immunochemotherapy

- Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with
any other investigational anti-cancer agent within 4 weeks prior to study treatment at
Cycle 1/Day 1 infusion

- Prior solid organ transplantation

- Prior allogeneic stem cell transplantation

- Autologous stem cell transplantation within 100 days prior to Cycle 1/Day 1

- Prior treatment with CAR T-cell therapy within 30 days prior to study treatment at
Cycle 1 Day 1

- History of autoimmune disease

- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibody therapy (or recombinant antibody-related fusion proteins)

- A history of confirmed progressive multifocal leukoencephalopathy

- Current or past history of central nervous system (CNS) lymphoma

- Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who
received corticosteroid treatment with </=30 mg/day of prednisone or equivalent must
be documented to be on a stable dose of at least 4 weeks' duration prior to Cycle
1/Day 1. Participants may have received a brief (<7 days) course of systemic steroids
(</=100 mg prednisone equivalent per day) prior to initiation of study therapy for
control of lymphoma-related symptoms

- Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or
neurodegenerative 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 (bronchospasm, obstructive pulmonary
disease), and known autoimmune diseases

- Major surgery or significant traumatic injury < 28 days prior to the study treatment
infusion at Cycle 1/Day 1 (excluding biopsies) or anticipation of the need for major
surgery during study treatment

- Participants with another invasive malignancy that could affect compliance with the
protocol or interpretation of results

- Significant or extensive cardiovascular disease

- Left ventricular ejection fraction < 50%

- Administration of a live, attenuated vaccine within 4 weeks before study treatment
infusion on Cycle 1 Day 1 or anticipation that such a live, attenuated vaccine will be
required during the study

- History of illicit drug or alcohol abuse within 12 months prior to screening, in the
Investigator's judgment

- Any other diseases, metabolic dysfunction, physical examination finding (including
mental status), or clinical laboratory finding giving reasonable suspicion of a
disease or condition that would contraindicate the use of an investigational drug

- Participants with latent or active tuberculosis

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

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/10/2024
Actual
Sample size
Target
172
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
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
West Virginia
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
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
Nantes
Country [9] 0 0
France
State/province [9] 0 0
Rouen
Country [10] 0 0
Germany
State/province [10] 0 0
Erlangen
Country [11] 0 0
Germany
State/province [11] 0 0
Freiburg
Country [12] 0 0
Germany
State/province [12] 0 0
Ulm
Country [13] 0 0
Germany
State/province [13] 0 0
Würzburg
Country [14] 0 0
Italy
State/province [14] 0 0
Campania
Country [15] 0 0
Italy
State/province [15] 0 0
Emilia-Romagna
Country [16] 0 0
Italy
State/province [16] 0 0
Lombardia
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Nottingham
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Plymouth

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 1B, multi-center, dose-finding study of glofitamab administered in
combination with obinutuzumab (Gazyva; [G]), rituximab (R) and standard doses of CHOP
(G/R-CHOP or R-CHOP) in participants with r/r NHL and G/R CHOP or Pola-R-CHP in participants
with untreated diffuse large B-cell lymphoma (DLBCL). Evaluating the safety, preliminary
activity, pharmacokinetic (PK), and pharmacodynamic effects of this combination will be the
main objectives of this study. The study is divided in two parts:

- Part I: Dose finding in participants with r/r NHL; test use of G vs R in Cycle 1

- Part II: Dose Expansion. The maximum tolerated dose or optimal biological dose (MTD or
OBD) will be further assessed in participants with untreated DLBCL (>18 years of age
with an age-adjusted International Prognostic Index (IPI) of 2-5). Glofitamab will be
studied in combination with R-CHOP and Pola-R-CHP.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03467373
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03467373