For Healthcare Professionals

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

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About the study

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.
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Who can take part

You may be eligible to participate in the study if you meet the following criteria:

INCLUSION CRITERIA

Inclusion Criteria:


  1. Age >/=18 years
  2. 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
  3. For Part II untreated DLBCL expansion: Histologically confirmed previously-untreated DLBCL that is expected to express CD20
  4. Able to provide a pretreatment biopsy between the final dose of last prior therapy and initiation of study medication at Cycle 1/Day 1
  5. 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.
  6. Participants must have at least one measurable target lesion (> or = 1.5 cm) in its largest dimension by computed tomography (CT) scan
  7. 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
  8. Life expectancy (in the opinion of the Investigator) of 18 weeks
  9. Adverse events (AEs) from prior anti-cancer therapy must have resolved to Grade
  10. Adequate liver function
  11. Adequate hematological function
  12. Adequate renal function
  13. Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
  14. Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV)

EXCLUSION CRITERIA

Exclusion Criteria:


  1. Inability to comply with protocol mandated hospitalization and restrictions
  2. 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
  3. 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
  4. 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)
  5. 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
  6. Contraindication to any of the individual components of the immunochemotherapy
  7. 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
  8. Prior solid organ transplantation
  9. Prior allogeneic stem cell transplantation
  10. Autologous stem cell transplantation within 100 days prior to Cycle 1/Day 1
  11. Prior treatment with CAR T-cell therapy within 30 days prior to study treatment at Cycle 1 Day 1
  12. History of autoimmune disease
  13. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  14. A history of confirmed progressive multifocal leukoencephalopathy
  15. Current or past history of central nervous system (CNS) lymphoma
  16. Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who received corticosteroid treatment with
  17. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  18. 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
  19. 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
  20. Participants with another invasive malignancy that could affect compliance with the protocol or interpretation of results
  21. Significant or extensive cardiovascular disease
  22. Left ventricular ejection fraction < 50%
  23. 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
  24. History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator's judgment
  25. 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
  26. Participants with latent or active tuberculosis

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Study Locations

Enter your ZIP code/Postal code/PIN code to locate study sites near you:

How to Apply


Contact the study center to learn if this study is a good match for you.

Study’s details


Contition

B-Cell Lymphoma,Non-Hodgkin Lymphoma

Age (in years)

18+

Phase

Phase 1

Participants needed

172

Est. Completion Date

Oct 30, 2024

Treatment type

Interventional


Sponsor

Hoffmann-La Roche

ClinicalTrials.gov identifier

NCT03467373

Study number

NP40126

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