A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma Clinical Trial

Official title:

Phase 1b/2, Open-Label Study to Evaluate Safety and Tolerability of Epcoritamab in Combination With Anti-Neoplastic Agents in Subjects With Non-Hodgkin Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05283720
• Other study ID #: M22-132
• Secondary ID: 2021-005725-24
• Status: Recruiting
• Phase: Phase 2
• Start date: June 14, 2022
• Est. completion date: November 26, 2032

Study information

• Verified date: June 2024
• Source: Genmab
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cell (a white blood cell responsible for fighting infections). The purpose of this study is to assess the safety and tolerability of epcoritamab in combination with anti-neoplastic agents in adult participants with Non-Hodgkin lymphoma (NHL). Adverse events and change in disease activity will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of NHL. Study doctors put the participants in groups called treatment arms. The combination of epcoritamab with anti-neoplastic agents will be explored. Each treatment arm receives a different treatment combination depending on eligibility. Approximately 394 adult participants with NHL will be enrolled in 100 sites globally.

In both the dose escalation and dose expansion arms participants will receive subcutaneous (SC) epcoritamab in 28-day or 21 day cycles dependent on the arm in combination with the anti-neoplastic agents described below:

1: Oral lenalidomide in participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL); 2: Oral ibrutinib and oral lenalidomide in participants with with R/R DLBCL; 3: Intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in participants with newly diagnosed treatment-naïve DLBCL; 4: Oral CC-99282 in participants with R/R DLBCL; 5: Oral CC-99282 in participants with R/R follicular lymphoma (FL); 6A: Oral ibrutinib in participants with R/R mantle cell lymphoma (MCL); 6B: Oral ibrutinib, and oral venetoclax in participants with R/R MCL; 7: Oral ibrutinib, and oral venetoclax in participants with newly diagnosed treatment-naïve MCL.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 394
• Est. completion date: November 26, 2032
• Est. primary completion date: November 26, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of:

-- Diffuse large B-cell lymphoma (DLBCL) (de novo or histologically transformed from follicular lymphoma (FL) or nodal marginal zone lymphoma) with histologically confirmed CD20+ disease, inclusive of the following according to World Health Organization (WHO) 2016 classification and documented in pathology report:

• DLBCL, not otherwise specified (NOS).

• High-grade B cell lymphoma with MYC and BCL-2 and/or BCL-6 translocations per WHO 2016 ("double-hit" or "triple-hit") Note: High-grade B-cell lymphomas NOS or other double- /triple-hit lymphomas (with histologies not consistent with DLBCL) are not eligible.

• Follicular lymphoma (FL) Grade 3B. OR

• FL with histologically confirmed CD20+ Grade 1 to 3a and no evidence of histologic transformation to an aggressive lymphoma at most recent representative tumor biopsy, according to WHO 2016 classification. OR

• Mantle cell lymphoma (MCL) with histologically confirmed CD20+ disease at most recent representative tumor biopsy according to the WHO 2016 classification with evidence of overexpression of cyclin D1 in association with relevant markers or evidence of t(11;14) assessed by flow cytometry, FISH, or polymerase chain reaction (PCR).

• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2, except for Arms 6 and 7 where ECOG performance status must be 0-1.

• Must have 1 or more measurable disease sites:

• A positron emission tomography (PET) /computed tomography (CT) scan demonstrating PET-positive lesion(s) AND

• At least 1 measurable nodal lesion (long axis > 1.5 cm) or >= 1 measurable extra-nodal lesion (long axis > 1.0 cm) on CT scan or magnetic resonance imaging (MRI).

Exclusion Criteria:

• Prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD20.

• Toxicities from prior anticancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Events (CTCAE, v 5.0), Grade 2 or below, with the exception of alopecia. Other eligibility criteria (e.g., laboratory, cardiac criteria) must also be met.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

Intervention

Drug:
• Epcoritamab
Subcutaneous Injection (SC)
• Lenalidomide
Oral; Capsule
• Ibrutinib
Oral; Capsule
• Rituximab
Intravenous (IV); Injection
• Cyclophosphamide
IV; Injection
• Doxorubicin Hydrochloride [HCl]
IV; Injection
• Prednisone
Oral; Tablet
• Polatuzumab Vedotin
IV; Injection
• Venetoclax
Oral; Tablet
• CC-99282
Oral; Capsule

Locations

Country	Name	City	State
Czechia	Fakultni nemocnice Brno /ID# 242683	Brno
Czechia	Fakultni nemocnice Hradec Kralove /ID# 241722	Hradec Kralove
Czechia	Fakultni Nemocnice Ostrava /ID# 242684	Ostrava
Czechia	Vseobecna fakultni nemocnice v Praze /ID# 242685	Praha
Denmark	Aalborg University Hospital /ID# 242734	Aalborg	Nordjylland
Denmark	Aarhus Universitetshospital - Skejby /ID# 242670	Aarhus	Midtjylland
France	CHU Clermont-Ferrand /ID# 242344	Clermont	Auvergne-Rhone-Alpes
France	Hopitaux Universitaires Henri Mondor - Hopital Henri Mondor /ID# 242337	Creteil	Paris
France	CHRU Lille - Hopital Claude Huriez /ID# 242335	Lille	Nord
France	CHU de Nantes, Hotel Dieu -HME /ID# 242345	Nantes	Pays-de-la-Loire
France	Hopital Pitie Salpetriere /ID# 242343	Paris
France	Institut de Recherche Saint Louis - Hopital St Louis /ID# 242336	Paris	Ile-de-France
France	HCL - Hopital Lyon Sud /ID# 242349	Pierre Benite CEDEX	Rhone
France	CHU de Rennes - PONTCHAILLOU /ID# 242339	Rennes	Bretagne
France	IUCT Oncopole /ID# 242340	Toulouse Cedex 9
France	CHRU Nancy - Hopitaux de Brabois /ID# 242342	Vandoeuvre-les-Nancy	Meurthe-et-Moselle
Germany	Klinikum Augsburg /ID# 244523	Augsburg	Bayern
Germany	Universitaetsklinikum Leipzig /ID# 245513	Leipzig	Sachsen
Germany	Universitaetsklinikum Giessen und Marburg /ID# 245308	Marburg
Germany	Universitaetsklinikum Regensburg /ID# 244517	Regensburg
Germany	Universitaetsklinikum Ulm /ID# 244265	Ulm	Baden-Wuerttemberg
Germany	Universitaetsklinikum Wuerzburg /ID# 245453	Wuerzburg
Hungary	Orszagos Onkologiai Intezet /ID# 242458	Budapest
Hungary	Semmelweis Egyetem /ID# 242454	Budapest
Hungary	Debreceni Egyetem-Klinikai Kozpont /ID# 242450	Debrecen	Hajdu-Bihar
Hungary	Somogy Varmegyei Kaposi Mor Oktato Korhaz /ID# 245935	Kaposvár	Somogy
Israel	Rabin Medical Center /ID# 243014	Haifa
Israel	Hadassah Medical Center-Hebrew University /ID# 243013	Jerusalem	Yerushalayim
Israel	The Chaim Sheba Medical Center /ID# 243010	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 243012	Tel Aviv	Tel-Aviv
Japan	National Cancer Center Hospital /ID# 248995	Chuo-ku	Tokyo
Japan	Kyoto University Hospital /ID# 248997	Kyoto-shi	Kyoto
Japan	Hokkaido University Hospital /ID# 248999	Sapporo-shi	Hokkaido
Korea, Republic of	Seoul National University Bundang Hospital /ID# 242404	Seongnam-si	Gyeonggido
Korea, Republic of	Asan Medical Center /ID# 242400	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center /ID# 242401	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 242402	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Marys Hospital /ID# 242403	Seoul	Seoul Teugbyeolsi
Netherlands	Vrije Universiteit Medisch Centrum /ID# 243319	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen /ID# 243318	Groningen
Netherlands	Leids Universitair Medisch Centrum /ID# 243316	Leiden
Netherlands	Maastricht Universitair Medisch Centrum /ID# 243317	Maastricht
Netherlands	Duplicate_Erasmus Medisch Centrum /ID# 243315	Rotterdam	Zuid-Holland
Spain	Instituto Catalan de Oncologia (ICO) Badalona /ID# 243265	Badalona	Barcelona
Spain	Hospital Universitario Vall d'Hebron /ID# 243260	Barcelona
Spain	Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 243261	L'Hospitalet de Llobregat	Barcelona
Spain	CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 243268	Madrid
Spain	Hospital Universitario 12 de Octubre /ID# 243262	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 243264	Madrid
Spain	Clinica Universidad de Navarra - Pamplona /ID# 245031	Pamplona	Navarra
Spain	Hospital Universitario de Salamanca /ID# 243368	Salamanca
Spain	Hospital Universitario Virgen del Rocio /ID# 243267	Sevilla
Spain	Hospital Clinico Universitario de Valencia /ID# 243269	Valencia
Taiwan	China Medical University Hospital /ID# 242893	Taichung
Taiwan	National Cheng Kung University Hospital /ID# 242894	Tainan
Taiwan	Taipei Veterans General Hosp /ID# 242892	Taipei
United States	Emory University /ID# 242153	Atlanta	Georgia
United States	University of Maryland Medical Center /ID# 242218	Baltimore	Maryland
United States	Novant Health Presbyterian Medical Center /ID# 242148	Charlotte	North Carolina
United States	East Carolina University - Brody School of Medicine /ID# 242506	Greenville	North Carolina
United States	Alliance for Multispecialty Research (AMR) - Kansas City /ID# 242144	Kansas City	Missouri
United States	Thompson Cancer Survival Ctr /ID# 242150	Knoxville	Tennessee
United States	Northwell Health - Monter Cancer Center /ID# 245435	Lake Success	New York
United States	Joe Arrington Cancer Research /ID# 242226	Lubbock	Texas
United States	Yale University School of Medicine /ID# 242089	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai /ID# 242123	New York	New York
United States	Christiana Care Health Service /ID# 242301	Newark	Delaware
United States	Fox Chase Cancer Center /ID# 242106	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital /ID# 242077	Philadelphia	Pennsylvania
United States	Swedish Cancer Institute- First Hill /ID# 242269	Seattle	Washington
United States	MultiCare Institute for Research & Innovation /ID# 242127	Tacoma	Washington
United States	Tampa General Hospital /ID# 246748	Tampa	Florida
United States	University of Arizona Cancer Center - North Campus /ID# 242219	Tucson	Arizona
United States	Novant Health Forsyth Medical Center /ID# 242198	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	AbbVie

Countries where clinical trial is conducted

United States,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose-Limiting Toxicities (DLT)	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to Approximately 5 Years
Secondary	Best Overall Response (BOR) per Investigator	BOR is defined as the percentage of participants who achieved best overall response of CR or PR by Lugano 2014 criteria as assessed by the investigator.	Up to Approximately 5 Years
Secondary	Duration of response (DOR) per Investigator	DOR is defined for participants who achieved best overall response of CR or PR ('responders'), as the time in months from initial CR/PR to the earliest occurrence of radiographic progression determined by Lugano 2014 criteria as assessed by the investigator, or death from any cause.	Up to Approximately 5 Years
Secondary	Number of Participants with Progression-free survival (PFS)	PFS is defined as the time in months from the first dose of study drug to the earliest occurrence of disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.	Up to Approximately 5 Years
Secondary	Percentage of Participants with Complete Response (CR)	CR is defined as the percentage of participantswho achieved best overall response of CR determined by Lugano 2014 criteria as assessed by investigator.	Up to Approximately 5 Years
Secondary	Time-to-response (TTR)	TTR is defined as the number of months from the date of first dose to the date of best overall response of CR or PR ('responders') determined by Lugano 2014 criteria as assessed by investigator.	Up to Approximately 5 Years
Secondary	Time to Next Antilymphoma Therapy (TTNT)	Time to next antilymphoma therapy.	Up to Approximately 5 Years
Secondary	Rate of Minimal Residual Disease (MRD) Negativity	MRD is defined as the percentage of participants with assessment of the minimal residual disease.	Up to Approximately 5 Years
Secondary	Overall Survival (OS)	(OS) is defined as the time in months from first dose of epcoritamab to death from any cause.	Up to Approximately 5 Years