A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and CC-99282 in Participants With B-Cell Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma Clinical Trial

Official title:

A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and CC-99282 in Patients With B-Cell Non-Hodgkin Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05169515
• Other study ID #: CO43805
• Status: Recruiting
• Phase: Phase 1
• Start date: October 26, 2022
• Est. completion date: July 15, 2028

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: CO43805 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety, efficacy, and pharmacokinetics of mosunetuzumab or glofitamab in combination with CELMoDs (CC-220 or CC-99282) in participants with B-cell NHL.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 121
• Est. completion date: July 15, 2028
• Est. primary completion date: July 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >/= 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• History of one of the following histologically documented hematologic malignancies that are expected to express the CD20 antigen: In the Dose Escalation phase, patients with R/R NHL who previously received at least two prior lines of systemic therapies can be enrolled. In the Dose Expansion phase, patients with FL (grade 1-3a), DLBCL/transformed FL who failed to respond to at least one prior line of systemic therapy can be potentially enrolled
• Fluorodeoxyglucose-avid lymphoma (i.e. PET-positive lymphoma)
• At least one bi-dimensionally measurable nodal lesion (> 1.5 cm in its largest dimension by diagnostic quality CT or PET/CT scan), or at least one bi-dimensionally measurable extranodal lesion (> 1.0 cm in its largest dimension by diagnostic quality CT or PET/CT scan)
• Availability of a representative tumor specimen and the corresponding pathology report for confirmation of the diagnosis of NHL
• A fresh pretreatment biopsy during screening period, excisional or incisional, is preferred
• Adequate hematologic function without growth factors or blood product transfusion within 14 days of first dose of study drug administration
• Normal laboratory values
• All participants and health care providers will be trained and counseled on pregnancy prevention. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 3 months after the final dose of mosunetuzumab, at least 18 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, 28 days after the last dose of CC-220, 6 months and 2 weeks after the last dose of CC-99282, 3 months after the last dose of tocilizumab (if applicable), whichever is longer
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, 90 days after the last dose of CC-220, 3 months and 2 weeks after the last dose of CC- 99282, 2 months after the final dose of tocilizumab (if applicable), whichever is longer

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study (female participants of childbearing potential must have a negative serum pregancy test result within 14 days prior to initiation of the study treatment)
• Participant has received prior therapy with cereblon (CRBN)-modulating drug (e.g., lenalidomide, avadomide/CC-122, pomalidomide) </= 4 weeks prior to starting CC-220 and/or CC-99282
• Inability to swallow pills, or persistent diarrhea or malabsorption >= Grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), despite medical management
• QTc interval of > 470 ms
• The following treatments prior to study entry: mosunetuzumab, glofitamab, or other CD20/CD3-directed bispecific antibodies; allogenic stem cell therapy (SCT); solid organ transplantation
• Treatments (investigation or approved) within the following time periods prior to initiation/first dose of study treatment: radiotherapy within 2 weeks; autologous SCT within 100 days; chimeric antigen receptor (CAR) T-cell therapy within 30 days; prior anti-lymphoma treatment with monoclonal antibodies or antibody-drug conjugates within 4 weeks; use of radioimmunoconjugates within 12 weeks; systemic immunosuppressive medications within 2 weeks; any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter
• Live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment
• Current or past history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• Major surgery or significant traumatic injury < 28 days prior to enrollment (excluding biopsies) or anticipation of the need for major surgery during study treatment
• Clinically significant toxicities from prior treatment have not resolved to Grade </= 1 (per US national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5.0) prior to the first study drug administration with exceptions defined by the protocol
• Evidence of any significant, concomitant disease (e.g. cardiovascular, pulmonary, liver, CVA or stroke, ILD, PML, infection, HLH etc) that could affect compliance with the protocol or interpretation of results
• For participants enrolled into glofitamab cohort: documented refractoriness to an obinutuzumab monotherapy-containing regimen (defined as disease that did not achieve response (PR or CR) or progressed within 6 months of the last dose of an obinutuzumab-containing regimen)

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

Intervention

Drug:
• SC Mosunetuzumab
Participants will receive SC mosunetuzumab for 12 cycles (cycle length = 21 days for Cycle 1 and 28 days for Cycles 2-12)
• IV Glofitamab
Participants will receive IV glofitamab for 12 cycles (cycle length = 21 days)
• CC-220
Arm 1: Participants will receive oral CC-220 from Day 1-21 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12)
• CC-99282
Arm 1: Participants will receive oral CC-99282 from Day 1-14 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12) Arm 2: Participants will receive oral CC-99282 from Day 1-10 of Cycle 3-12 (cycle length = 21 days)
• Obinutuzumab
Participants in Arm 2 will receive pre-treatment with IV obinutuzumab on Cycle 1 Day 1 (cycle length = 21 days)
• Tocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS)

Locations

Country	Name	City	State
Israel	Soroka	Be'er Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Center; Pulmonary Institute	Jerusalem
Israel	Center Hospital	Ramat Gan
Israel	Sourasky Medical Center; Oncology Department	Tel-Aviv
Italy	IRCCS Azienda Ospedaliero Universitaria di Bologna	Bologna	Emilia-Romagna
Italy	ASST Spedali Civili di Brescia	Brescia	Lombardia
Italy	IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"	Meldola	Emilia-Romagna
Italy	Irccs Ospedale San Raffaele;U.O. Oculistica	Milano	Lombardia
Italy	Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia	Pisa	Piemonte
Spain	Hospital Universitari Vall d Hebron	Barcelona
Spain	ICO L'Hospitalet; Servicio de Farmacia	L'Hospitalet de Llobregat	Barcelona
Spain	Clinica Universidad de Navarra-Madrid	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hosp Universitario Salamanca	Salamanca
Spain	Hospital Universitario La Fe; Hospital La Fe	València	Valencia
United Kingdom	Western General Hospital; Edinburgh Cancer Center	Edinburgh
United Kingdom	NHS Greater Glasgow and Clyde; Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	University College London Hospitals	London
United Kingdom	Nottingham University Hospitals City Campus; Nottingham Cancer Clinical Trials Team	Nottingham
United Kingdom	Oxford University Hospitals NHS Trust; Churchill Hospital; Clinical Trials Pharmacy Department	Oxford
United States	University of Colorado	Aurora	Colorado
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	The University of Chicago	Chicago	Illinois
United States	UT MD Anderson Cancer Center; Investigational Pharmacy	Houston	Texas
United States	UCSF/Hematology, Blood & Marrow Transplant, And Cellular Therapy (HBC) Program	San Francisco	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Israel,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with dose-limiting toxicities (DLTs) [dose escalation]		Until 90 days after the final dose of study treatment
Primary	Percentage of participants with adverse events [dose escalation]		Until 90 days after the final dose of study treatment
Primary	Best overall response rate (ORR), defined as the proportion of participants whose best overall response is a partial response (PR) or a complete response (CR) during the study, as determined by the investigator using Lugano 2014 criteria [dose expansion]		Up to 1 year after start of primary study treatment
Secondary	Best CR rate, defined as the proportion of participants whose best overall response is a CR during the study, as determined by the investigator using Lugano 2014 criteria [all cohorts]		Up to 1 year after primary study treatment
Secondary	Best ORR (CR or PR at any time) on study as determined by the investigator using Lugano 2014 criteria [dose escalation]		Up to 2 years after primary study treatment
Secondary	Duration of response (DOR) as determined by the investigator using Lugano 2014 criteria [all cohorts]		Up to 2 years after primary study treatment
Secondary	Progression-free survival (PFS) as determined by the investigator using Lugano 2014 criteria [dose expansion]		Up to 2 years after primary study treatment
Secondary	Event-free survival (EFS) as determined by the investigator using Lugano 2014 criteria [dose expansion]		Up to 2 years after primary study treatment
Secondary	Overall survival (OS) [dose expansion]		Up to 2 years after primary study treatment
Secondary	Percentage of participants with adverse events [dose expansion]		Until 90 days after the final dose of study treatment
Secondary	Serum concentration of subcutaneous (SC) mosunetuzumab [all cohorts]		Up to 2 years after primary study treatment
Secondary	Serum concentration of intravenous (IV) glofitamab [all cohorts]		Up to 2 years after primary study treatment
Secondary	Serum concentration of CC-220 and CC-99282 (CELMoDs) [all cohorts]		Up to 12 cycles of study treatment (cycle length = 21 or 28 days for Arm 1 and 21 days for Arm 2)