Clinical trial NCT05283720: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin Lymphoma
Keywords: Non-Hodgkin Lymphoma
Epcoritamab
Lenalidomide
Ibrutinib
Polatuzumab Vedotin
Rituximab
Cyclophosphamide
Doxorubicin Hydrochloride (HCl]
Prednisone (pola-R-CHP)
ABBV-GMAB-3013
Cancer
Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL), Venetoclax,
Venclexta
ABT-199
GDC-0199
CC-99282
EPCORE
Pirtobrutinib
Mantle Cell Lymhoma
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2022-03-17
Enrollment: 565
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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 565 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, 21 day, or 56 day cycles dependent on the arm in combination with the anti-neoplastic agents described below:

1: Oral lenalidomide in participants (PPTS) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL); 2: Oral ibrutinib and oral lenalidomide in PPTS 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 PPTS with newly diagnosed treatment-naïve DLBCL; 4: Oral CC-99282 in PPTS with R/R DLBCL; 5: Oral CC-99282 in PPTS with R/R follicular lymphoma (FL); 6A: Oral ibrutinib in PPTS with R/R mantle cell lymphoma (MCL); 6B: Oral ibrutinib, and oral venetoclax in PPTS with R/R MCL; 7: Oral ibrutinib, and oral venetoclax in PPTS with newly diagnosed treatment-naïve MCL. 8: Oral pirtobrutinib in PPTS with R/R 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.


Eligibility criteria: 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, fluorescence in situ hybridization (FISH), or polymerase chain reaction (PCR).
* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2, except for Arms 6, 7, and 8 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 that have 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.

Primary outcomes:
measure: Number of Participants with Dose-Limiting Toxicities (DLT)
timeFrame: Up to Approximately 5 Years
Secondary outcomes:
measure: Best Overall Response (BOR) per Investigator
timeFrame: Up to Approximately 5 Years
measure: Duration of response (DOR) per Investigator
timeFrame: Up to Approximately 5 Years
measure: Number of Participants with Progression-free survival (PFS)
timeFrame: Up to Approximately 5 Years
measure: Percentage of Participants with Complete Response (CR)
timeFrame: Up to Approximately 5 Years
measure: Time-to-response (TTR)
timeFrame: Up to Approximately 5 Years
measure: Time to Next Antilymphoma Therapy (TTNT)
timeFrame: Up to Approximately 5 Years
measure: Rate of Minimal Residual Disease (MRD) Negativity
timeFrame: Up to Approximately 5 Years
measure: Overall Survival (OS)
timeFrame: Up to Approximately 5 Years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center - North Campus /ID# 242219
state: Arizona
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 242089
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Health Service /ID# 242301
state: Delaware
city: Tampa
country: United States
facility: Tampa General Hospital /ID# 246748
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University /ID# 242153
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland, Baltimore /ID# 242218
state: Maryland
city: Kansas City
country: United States
facility: Alliance for Multispecialty Research (AMR) - Kansas City /ID# 242144
state: Missouri
city: Lake Success
country: United States
facility: Northwell Health - Monter Cancer Center /ID# 245435
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai /ID# 242123
state: New York
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center /ID# 242148
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University - Brody School of Medicine /ID# 242506
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Forsyth Medical Center /ID# 242198
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital /ID# 242077
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center /ID# 242106
state: Pennsylvania
city: Knoxville
country: United States
facility: Thompson Cancer Survival Ctr /ID# 242150
state: Tennessee
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research /ID# 242226
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute /ID# 242269
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation /ID# 242127
state: Washington
city: Brno
country: Czechia
facility: Fakultní Nemocnice Brno - Jihlavská /ID# 242683
state: Brno-mesto
city: Hradec Králové
country: Czechia
facility: Fakultní nemocnice Hradec Králové - Sokolská /ID# 241722
state: Hradec Kralove
city: Ostrava
country: Czechia
facility: Fakultni Nemocnice Ostrava /ID# 242684
state: Ostrava-mesto
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze /ID# 242685
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital - Skejby /ID# 242670
state: Midtjylland
city: Aalborg
country: Denmark
facility: Aalborg University Hospital /ID# 242734
state: Nordjylland
city: Clermont
country: France
facility: CHU Clermont-Ferrand /ID# 242344
state: Auvergne-Rhone-Alpes
city: Rennes
country: France
facility: CHU de Rennes - PONTCHAILLOU /ID# 242339
state: Bretagne
city: Paris Cedex 13
country: France
facility: Hopital Pitie Salpetriere /ID# 242343
state: Ile-de-France
city: Vandoeuvre-les-Nancy
country: France
facility: CHRU Nancy - Hopitaux de Brabois /ID# 242342
state: Meurthe-et-Moselle
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez /ID# 242335
state: Nord
city: Toulouse Cedex 9
country: France
facility: IUCT Oncopole /ID# 242340
state: Occitanie
city: Creteil
country: France
facility: Hopitaux Universitaires Henri Mondor - Hopital Henri Mondor /ID# 242337
state: Paris
city: Nantes
country: France
facility: CHU de Nantes, Hotel Dieu -HME /ID# 242345
state: Pays-de-la-Loire
city: Pierre Benite CEDEX
country: France
facility: HCL - Hopital Lyon Sud /ID# 242349
state: Rhone
city: Paris
country: France
facility: Hôpital Saint-Louis /ID# 242336
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm /ID# 244265
state: Baden-Wuerttemberg
city: Augsburg
country: Germany
facility: Klinikum Augsburg /ID# 244523
state: Bayern
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg /ID# 245453
state: Bayern
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg /ID# 245308
state: Hessen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig /ID# 245513
state: Sachsen
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg /ID# 244517
city: Debrecen
country: Hungary
facility: Debreceni Egyetem-Klinikai Kozpont /ID# 242450
state: Hajdu-Bihar
city: Kaposvár
country: Hungary
facility: Somogy Varmegyei Kaposi Mor Oktato Korhaz /ID# 245935
state: Somogy
city: Budapest
country: Hungary
facility: Semmelweis Egyetem /ID# 242454
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet /ID# 242458
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 243010
state: Tel-Aviv
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 243012
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 243013
state: Yerushalayim
city: Petah Tikva
country: Israel
facility: Rabin Medical Center /ID# 243014
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital /ID# 248999
state: Hokkaido
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital /ID# 248997
state: Kyoto
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 248995
state: Tokyo
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital /ID# 242404
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 242402
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 242400
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 242401
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Marys Hospital /ID# 242403
state: Seoul Teugbyeolsi
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum /ID# 243317
state: Limburg
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum /ID# 243319
state: Noord-Holland
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum /ID# 243316
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Duplicate_Erasmus Medisch Centrum /ID# 243315
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen /ID# 243318
city: Badalona
country: Spain
facility: Instituto Catalan de Oncologia (ICO) Badalona /ID# 243265
state: Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 243261
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona /ID# 245031
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 243260
city: Madrid
country: Spain
facility: CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 243268
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 243264
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 243262
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca /ID# 243368
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 243267
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 243269
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 242893
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 242894
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 242892
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: