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
Study Details
Study Description
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 132 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 combination with anti-neoplastic agents in 28-day cycles for arms 1 and 2 and 21- day cycles for arm 3.
Arm 1: SC epcoritamab in combination with oral lenalidomide in participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Arm 2: SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in participants with with R/R DLBCL.
Arm 3: SC epcoritamab in combination with 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.
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm 1: Dose Escalation Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of subcutaneous (SC) epcoritamab in combination with oral lenalidomide in 28 day cycles. |
Drug: Epcoritamab
Subcutaneous Injection (SC)
Other Names:
Drug: Lenalidomide
Oral; Capsule
|
Experimental: Arm 2: Dose Escalation Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles. |
Drug: Epcoritamab
Subcutaneous Injection (SC)
Other Names:
Drug: Lenalidomide
Oral; Capsule
Drug: Ibrutinib
Oral; Capsule
|
Experimental: Arm 3: Dose Escalation Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles. |
Drug: Epcoritamab
Subcutaneous Injection (SC)
Other Names:
Drug: Rituximab
Intravenous (IV); Injection
Drug: Cyclophosphamide
IV; Injection
Drug: Doxorubicin Hydrochloride [HCl]
IV; Injection
Drug: Prednisone
Oral; Tablet
Drug: Polatuzumab
IV; Injection
|
Experimental: Arm 1: Dose Expansion Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral lenalidomide in 28 day cycles. |
Drug: Epcoritamab
Subcutaneous Injection (SC)
Other Names:
Drug: Lenalidomide
Oral; Capsule
|
Experimental: Arm 2: Dose Expansion Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles. |
Drug: Epcoritamab
Subcutaneous Injection (SC)
Other Names:
Drug: Lenalidomide
Oral; Capsule
Drug: Ibrutinib
Oral; Capsule
|
Experimental: Arm 3: Dose Expansion Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles. |
Drug: Epcoritamab
Subcutaneous Injection (SC)
Other Names:
Drug: Rituximab
Intravenous (IV); Injection
Drug: Cyclophosphamide
IV; Injection
Drug: Doxorubicin Hydrochloride [HCl]
IV; Injection
Drug: Prednisone
Oral; Tablet
Drug: Polatuzumab
IV; Injection
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Dose-Limiting Toxicities (DLT) [Up to Approximately 5 Years]
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.
Secondary Outcome Measures
- Overall Response Rate (ORR) per Investigator [Up to Approximately 5 Years]
Overall response rate (ORR) 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.
- Duration of response (DOR) per Investigator [Up to Approximately 5 Years]
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.
- Number of Participants with Progression-free survival (PFS) [Up to Approximately 5 Years]
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.
- Percentage of Participants with Complete Response (CR) [Up to Approximately 5 Years]
CR is defined as the percentage of participantswho achieved best overall response of CR determined by Lugano 2014 criteria as assessed by investigator.
- Time-to-response (TTR) [Up to Approximately 5 Years]
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.
- Time to Next Anti-Lymphoma Therapy (TTNT) [Up to Approximately 5 Years]
Time to next anti-lymphoma therapy.
- Rate of Minimal Residual Disease (MRD) Negativity [Up to Approximately 5 Years]
MRD is defined as the percentage of participants with assessment of the minimal residual disease.
- Overall Survival (OS) [Up to Approximately 5 Years]
(OS) is defined as the time in months from first dose of epcoritamab to death from any cause.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Diagnosis of diffuse large B-cell lymphoma (DLBCL) (de novo or histologically transformed from follicular lymphoma 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 Grade 3B.
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
-
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 >= 1.5cm and short axis > 1.0 cm) or >= 1 measurable extra-nodal lesion (long axis >= 1.0 cm) on CT scan or MRI.
Exclusion Criteria:
-
Prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD20.
-
Unresolved 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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Arizona Cancer Center - North Campus /ID# 242219 | Tucson | Arizona | United States | 85719-1478 |
2 | Yale University /ID# 242089 | New Haven | Connecticut | United States | 06510 |
3 | Christiana Care Health Service /ID# 242301 | Newark | Delaware | United States | 19713 |
4 | Tampa General Hospital /ID# 246748 | Tampa | Florida | United States | 33606 |
5 | Emory University /ID# 242153 | Atlanta | Georgia | United States | 30322-1013 |
6 | Augusta University Georgia Cancer Center /ID# 242140 | Augusta | Georgia | United States | 30912-0003 |
7 | Southern IL Univ School of Med /ID# 242229 | Springfield | Illinois | United States | 62702 |
8 | Univ Maryland School Medicine /ID# 242218 | Baltimore | Maryland | United States | 21201-1544 |
9 | Alliance for Multispecialty Research (AMR) - Kansas City /ID# 242144 | Kansas City | Missouri | United States | 64114-4859 |
10 | Roswell Park Comprehensive Cancer Center /ID# 242129 | Buffalo | New York | United States | 14263 |
11 | Northwell Health - Monter Cancer Center /ID# 245435 | Lake Success | New York | United States | 11042 |
12 | Icahn School of Medicine at Mount Sinai /ID# 242123 | New York | New York | United States | 10029-6504 |
13 | Novant Health Presbyterian Medical Center /ID# 242148 | Charlotte | North Carolina | United States | 28204 |
14 | East Carolina University Brody School of Medicine /ID# 242506 | Greenville | North Carolina | United States | 27834 |
15 | Novant Health Forsyth Medical Center /ID# 242198 | Winston-Salem | North Carolina | United States | 27103 |
16 | Gabrail Cancer Center Research /ID# 242212 | Canton | Ohio | United States | 44718 |
17 | Thomas Jefferson University /ID# 242077 | Philadelphia | Pennsylvania | United States | 19107-4414 |
18 | Fox Chase Cancer Center /ID# 242106 | Philadelphia | Pennsylvania | United States | 19111 |
19 | Thompson Cancer Survival Ctr /ID# 242150 | Knoxville | Tennessee | United States | 37916 |
20 | Joe Arrington Cancer Research /ID# 242226 | Lubbock | Texas | United States | 79410 |
21 | Swedish Cancer Institute - Edmonds /ID# 242269 | Seattle | Washington | United States | 98104 |
22 | Multicare Institute for Research and Innovation /ID# 242127 | Tacoma | Washington | United States | 98405 |
23 | BC Cancer - Vancouver /ID# 243946 | Vancouver | British Columbia | Canada | V5Z 1L3 |
24 | Fakultni Nemocnice Brno /ID# 242683 | Brno | Czechia | 625 00 | |
25 | Fakultni nemocnice Hradec Kralove /ID# 241722 | Hradec Kralove | Czechia | 500 05 | |
26 | Fakultni nemocnice Ostrava /ID# 242684 | Ostrava | Czechia | 708 52 | |
27 | Vseobecna fakultni nemocnice v Praze /ID# 242685 | Praha | Czechia | 128 08 | |
28 | Aarhus University Hospital /ID# 242670 | Aarhus N | Midtjylland | Denmark | 8200 |
29 | Aalborg University Hospital /ID# 242734 | Aalborg | Nordjylland | Denmark | 9000 |
30 | CHU Clermont-Ferrand /ID# 242344 | Clermont | Auvergne-Rhone-Alpes | France | 63100 |
31 | HCL - Hôpital Lyon Sud /ID# 242349 | Pierre Benite CEDEX | Auvergne-Rhone-Alpes | France | 69495 |
32 | CHU de Rennes - PONTCHAILLOU /ID# 242339 | Rennes | Bretagne | France | 35000 |
33 | CHRU Lille - Hopital Claude Huriez /ID# 242335 | Lille | Hauts-de-France | France | 59037 |
34 | Institut de Recherche Saint Louis - Hopital St Louis /ID# 242336 | Paris | Ile-de-France | France | 75010 |
35 | CHRU Nancy - Hôpitaux de Brabois /ID# 242342 | Vandœuvre-lès-Nancy | Meurthe-et-Moselle | France | 54500 |
36 | CHU de Nantes, Hotel Dieu -HME /ID# 242345 | Nantes | Pays-de-la-Loire | France | 44000 |
37 | Hopital Henri Mondor /ID# 242337 | Creteil | France | 94000 | |
38 | Hopital Pitie Salpetriere /ID# 242343 | Paris | France | 75013 | |
39 | IUCT Oncopole /ID# 242340 | Toulouse Cedex 9 | France | 31059 | |
40 | Universitaetsklinikum Ulm /ID# 244265 | Ulm | Baden-Wuerttemberg | Germany | 89081 |
41 | Universitatsklinikum Munster /ID# 248304 | Munster | Niedersachsen | Germany | 48149 |
42 | Universitaetsklinikum Koeln /ID# 244521 | Köln | Nordrhein-Westfalen | Germany | 50937 |
43 | Universitaetsklinikum Leipzig /ID# 245513 | Leipzig | Sachsen | Germany | 04103 |
44 | Klinikum Augsburg /ID# 244523 | Augsburg | Germany | 86156 | |
45 | Universitaetsklinikum Giessen und Marburg /ID# 245308 | Marburg | Germany | 35043 | |
46 | Universitaetsklinikum Regensburg /ID# 244517 | Regensburg | Germany | 93042 | |
47 | Universitaetsmedizin Rostock /ID# 244655 | Rostock | Germany | 18057 | |
48 | Universitaetsklinikum Wuerzburg /ID# 245453 | Wuerzburg | Germany | 97080 | |
49 | Debreceni Egyetem Klinikai Kozpont /ID# 242450 | Debrecen | Hajdu-Bihar | Hungary | 4032 |
50 | Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 245935 | Kaposvár | Somogy | Hungary | 7400 |
51 | Semmelweis Egyetem /ID# 242454 | Budapest | Hungary | 1085 | |
52 | Orszagos Onkologiai Intezet /ID# 242458 | Budapest | Hungary | 1122 | |
53 | The Chaim Sheba Medical Center /ID# 243010 | Ramat Gan | Tel-Aviv | Israel | 5265601 |
54 | Tel Aviv Sourasky Medical Center /ID# 243012 | Tel Aviv-Yafo | Tel-Aviv | Israel | 6423906 |
55 | Hadassah Medical Center-Hebrew University /ID# 243013 | Jerusalem | Israel | 91120 | |
56 | Rabin Medical Center /ID# 243014 | Petakh Tikva | Israel | 4941492 | |
57 | Seoul National University Bundang Hospital /ID# 242404 | Seongnam | Gyeonggido | Korea, Republic of | 13620 |
58 | Seoul National University Hospital /ID# 242402 | Seoul | Korea, Republic of | 03080 | |
59 | Asan Medical Center /ID# 242400 | Seoul | Korea, Republic of | 05505 | |
60 | Samsung Medical Center /ID# 242401 | Seoul | Korea, Republic of | 06351 | |
61 | The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 242403 | Seoul | Korea, Republic of | 06591 | |
62 | Erasmus Medisch Centrum /ID# 243315 | Rotterdam | Zuid-Holland | Netherlands | 3015 GD |
63 | Vrije Universiteit Medisch Centrum /ID# 243319 | Amsterdam | Netherlands | 1081 HV | |
64 | Universitair Medisch Centrum Groningen /ID# 243318 | Groningen | Netherlands | 9713 GZ | |
65 | Leids Universitair Medisch Centrum /ID# 243316 | Leiden | Netherlands | 2333 ZA | |
66 | Maastricht Universitair Medisch Centrum /ID# 243317 | Maastricht | Netherlands | 6229 HX | |
67 | Instituto Catalan de Oncologia (ICO) Badalona /ID# 243265 | Badalona | Barcelona | Spain | 08916 |
68 | Instituto Catalan de Oncologia (ICO) L'Hospitalet /ID# 243261 | Hospitalet de Llobregat | Barcelona | Spain | 08908 |
69 | CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 245031 | Pamplona | Navarra | Spain | 31008 |
70 | Hospital Universitario Vall d'Hebron /ID# 243260 | Barcelona | Spain | 08035 | |
71 | CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 243268 | Madrid | Spain | 28027 | |
72 | Hospital Universitario Fundacion Jimenez Diaz /ID# 243264 | Madrid | Spain | 28040 | |
73 | Hospital Universitario 12 de Octubre /ID# 243262 | Madrid | Spain | 28041 | |
74 | Hospital Universitario La Paz /ID# 243266 | Madrid | Spain | 28046 | |
75 | Hospital Universitario de Salamanca /ID# 243368 | Salamanca | Spain | 37711 | |
76 | Hospital Universitario Virgen del Rocio /ID# 243267 | Sevilla | Spain | 41013 | |
77 | Hospital Clinico Universitario de Valencia /ID# 243269 | Valencia | Spain | 46010 | |
78 | China Medical University Hospital /ID# 242893 | Taichung City | Taiwan | 40447 | |
79 | National Cheng Kung University Hospital /ID# 242894 | Tainan | Taiwan | 704 | |
80 | Taipei Veterans General Hosp /ID# 242892 | Taipei City | Taiwan | 11217 | |
81 | Leicester Royal Infirmary /ID# 246993 | Leicester | England | United Kingdom | LE1 5WW |
82 | Guys and St Thomas NHS Foundation Trust /ID# 245056 | London | London, City Of | United Kingdom | SE1 9RT |
83 | Imperial College Healthcare NHS Trust /ID# 245851 | London | United Kingdom | W2 1NY | |
84 | The Christie Hospital /ID# 243948 | Manchester | United Kingdom | M20 4BX |
Sponsors and Collaborators
- AbbVie
- Genmab
Investigators
- Study Director: ABBVIE INC., AbbVie
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- M22-132
- 2021-005725-24