A Phase II Study of Glofitamab Plus Polatuzumab-R-CHP for Patients With High-risk Diffuse Large B-cell Lymphoma

NCT05800366 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-606
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this research study is to evaluate the combination of study drugs, Glofitamab and Polatuzumab, and a standard chemotherapy regimen, R-CHP, as a treatment for high-risk diffuse large B-cell lymphoma. The names of the treatment interventions involved in this study are:

• Glofitamab (T-cell bispecific antibody)
• Polatuzumab (antibody-drug conjugate)
• R-CHP (a chemotherapy regimen comprised of Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, and Prednisone)

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Keywords

Lymphoma; High-risk diffuse large B-cell Lymphoma; Chemotherapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate

  The complete response (CR) Rate is the proportion of participants achieving CR based on Lugano criteria defined per protocol section 11.1.1 for target lesions.

  Baseline through 28 days post Cycle 8 of Glofitamab (each cycle is 21 days)

Secondary Outcomes (8)

• Dose-Limiting Toxicity (DLT)

  42 days

• Grade 3-5 Treatment-related Toxicity Rate

  Up to 9 months

• Overall Response Rate (ORR)

  8 months

• Median Duration of Response (DOR)

  Up to 24 months

• Median Progression-Free Survival (PFS)

  Up to 24 months

Study Arms (1)

Polatuzumab + Glofitamab + R-CH

EXPERIMENTAL

-Participants will receive treatment interventions as outlined: Experimental: Safety Lead-In Phase of 6 Participants, Total Enrollment of 40 Participants * Polatuzumab, once, predetermined day and dosage per cycle, per protocol Cycles 1 - 6 * R-CHP (Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Prednisone * Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride once, predetermined day and dosage per cycle, per protocol Cycles 1 - 6: * Prednisone) 5 days, predetermined day and dosage per cycle, per protocol Cycles 1 - 6: * Glofitamab * twice, predetermined day and dosage per cycle, per protocol Cycle 3-6 * once, predetermined day and dosage per cycle, per protocol Cycle 7-8 * Participants who need urgent therapy are also allowed to proceed with one cycle of R-CHOP for 1 cycle per standard of care. * Participants will be followed for up to 5 years post-treatment.

Drug: Glofitamab; Drug: Polatuzumab; Drug: Rituximab; Drug: Doxorubicin Hydrochloride; Drug: Cyclophosphamide; Drug: Prednisone

Interventions

Glofitamab DRUG

human IgG1-bispecific antibody, via IV infusion

Also known as: RO7082859

Polatuzumab + Glofitamab + R-CH

Polatuzumab DRUG

an antibody drug conjugate (ADC) that contains a humanized IgG1 anti-human CD79b monoclonal antibody, via IV infusion

Also known as: Polatuzumab vedotin, DCDS4501S, RG7596

Polatuzumab + Glofitamab + R-CH

Rituximab DRUG

Per standard care, via IV infusion

Also known as: Rituxan

Polatuzumab + Glofitamab + R-CH

Doxorubicin Hydrochloride DRUG

Per standard care, via IV infusion

Also known as: Hydroxydaunomycin

Polatuzumab + Glofitamab + R-CH

Cyclophosphamide DRUG

Per standard care, via IV infusion

Also known as: Cytophosphane, Cytoxan

Polatuzumab + Glofitamab + R-CH

Prednisone DRUG

Per standard care, orally

Also known as: Prednisolone, Methylprednisolone

Polatuzumab + Glofitamab + R-CH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses by 2016 WHO classification of lymphoid neoplasms
• DLBCL, not otherwise specified (NOS)
• T-cell/histiocyte-rich large B-cell lymphoma
• Epstein-Barr virus-positive DLBCL, NOS
• ALK-positive large B-cell lymphoma
• HHV8-positive DLBCL, NOS
• High-grade B-cell lymphoma (HGBCL), NOS
• HGBCL with translocations of MYC and BCL-2, or MYC and BCL-6
• Availability of archival (within 90 days) or freshly collected tumor tissue before study enrollment. If archival tissue is unavailable or is determined to be inadequate, tumor tissue must be obtained from a biopsy performed at screening, unless an exception is given after consultation with the principal investigator.
• IPI score of 2-5
• ECOG Performance Status of 0, 1, or 2 (see Appendix A)
• Greater than or equal to 18 years at the time of signing informed consent
• Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
• Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to the involvement of the spleen by DLBCL per the investigator), defined as follows:
• Hemoglobin ≥ 9.0 g/dL without transfusion for 14 days before first treatment

You may not qualify if:

• Contraindication to any of the individual components of study drugs, including prior receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products. Patients with a history of hypersensitivity to dexamethasone or systemic corticosteroids will also be excluded
• Prior organ transplantation
• History of indolent lymphoma or current diagnosis of the following: follicular lymphoma grade 3B; B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (grey-zone lymphoma); primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; CNS lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL
• Prior therapy for DLBCL with the exception of:
• Palliative, short-term treatment with corticosteroids (up to 7 days).
• One cycle of R-CHOP
• Prior radiotherapy to the mediastinal/pericardial region
• Prior treatment with cytotoxic drugs within 5 years of screening for any condition (e.g., cancer, rheumatoid arthritis) or prior use of any anti-CD20 antibody
• Prior use of any monoclonal antibody within 3 months of the start of Cycle 1; any investigational therapy within 28 days prior to the start of Cycle 1; vaccination with live vaccines within 28 days prior the start of Cycle 1
• Corticosteroid use \> 30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control. Patients receiving corticosteroid treatment with ≤ 30 mg/day of prednisone or equivalent for reasons other than lymphoma symptom control must be documented to be on a stable dose of at least 4 weeks' duration prior to the start of Cycle 1. Patients who require lymphoma symptom control during screening may receive steroids in the following manner: Up to 30 mg/day of prednisone or equivalent may be used for lymphoma symptom control during screening, including prior to finalization of staging (not included as part of pre-phase treatment). If glucocorticoid treatment is urgently required at higher doses for lymphoma symptom control prior to the start of study treatment, tumor assessments must be completed prior to initiation of \> 30 - 100 mg/day of prednisone or equivalent. Prednisone \> 30 - 100 mg/day or equivalent may be given for a maximum of 7 days as a pre-phase treatment. As part of the pre-phase treatment.
• History of other malignancies, except:
• Malignancy treated medically or surgically with curative intent and with no known active disease present for ≥2 years before the first dose of study drug
• Adequately treated skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease.
• Localized prostate cancer and low-risk prostate cancer on active surveillance (Gleason score 6 or below, stage 1 or 2)

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• Jennifer Crombie, MD: lead

Study Sites (3)

University of Miami Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

glofitamab; polatuzumab vedotin; Rituximab; Doxorubicin; Cyclophosphamide; Prednisone; Prednisolone; Methylprednisolone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols

Study Officials

• Jennifer Crombie, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clare Phinney

CONTACT

18572151517; clare_phinney@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 5, 2023
• Study Start: April 6, 2023
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2029
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)