A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab As Monotherapy or Combined With Standard of Care Therapies in Adult Participants in China With B-Cell Non-Hodgkin Lymphoma

B-Cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

Phase 1b/2, Open-Label Trial to Evaluate Safety and Preliminary Efficacy of Epcoritamab As Monotherapy or Combined With Standard-of-Care Therapies in Chinese Subjects With B-Cell Non-Hodgkin Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05201248
• Other study ID #: M21-103
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 10, 2022
• Est. completion date: December 13, 2024

Study information

• Verified date: June 2024
• Source: Genmab
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). The purpose of this study is to assess the safety and toxicity of epcoritamab as a monotherapy and when combined with standard of care therapy [Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or Rituximab and lenalidomide (R2)] in adult participants in China with B-Cell Non-Hodgkin Lymphoma. Adverse events and change in disease activity will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of B-Cell Non-Hodgkin Lymphoma. Study doctors put the participants in groups called treatment arms. A monotherapy of epcoritamab and two different combination of epcoritamab with standard of care therapy (R-CHOP or R2) will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. Approximately 66 adult participants with B-Cell Non-Hodgkin Lymphoma will be enrolled in the study in approximately 21 sites in China.

In the monotherapy arm (Cohort 1), participants will receive subcutaneous epcoritamab in 28-day cycles. In the combination arms (Cohorts 2 and 3), participants in Cohort 2 will receive subcutaneous epcoritamab with standard of care therapy (R-CHOP) in 21-day cycles followed by 28-day cycles, participants in Cohort 3 will receive subcutaneous epcoritamab with standard of care therapy (R2) in 28-day cycles.

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: Active, not recruiting
• Enrollment: 49
• Est. completion date: December 13, 2024
• Est. primary completion date: December 13, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

All Cohorts:

• Life expectancy of >= 3 months on standard of care (SOC).

• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2.

• Has one or more measurable disease sites:

• Fluorodeoxyglucose-positron emission tomography (FDGPET) scan demonstrating positive lesion compatible with computed tomography (CT) or magnetic resonance image (MRI)-defined anatomical tumor sites.

• >= 1 measurable nodal lesion (long axis > 1.5 cm and short axis > 1.0 cm) or >= 1.0 measurable extra-nodal lesion (long axis >= 1 cm) on CT scan or MRI. Note: A previously irradiated lesion must have demonstrated progression or residual disease in the lesion after radiotherapy to be considered measurable.

Cohort 1 Part 1 (Monotherapy Safety Run-in) Specific Criteria:

• Must have histologically confirmed CD20+ Diffuse large B-cell lymphoma (DLBCL), or High-grade B-cell lymphoma (HGCBL) with MYC and BCL2 and/or BCL6 translocations and DLBCL feature, and follicular Lymphoma (FL) at most recent (previous or current) representative tumor biopsy based on the pathology report, according to the World Health Organization (WHO) 2016 (or later) classification.

• Must have at least one prior treatment with an anti-CD20 monoclonal antibody (e.g., rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue.

• Must have relapsed or refractory disease. Note: Relapsed disease is defined as disease that has recurred >= 6 months after completion of therapy. Refractory disease is defined as disease that either progressed or failed to achieve an objective response during therapy or progressed within 6 months (<6 months) of completion of therapy.

Cohort 1 Part 2 (Monotherapy Expansion) Specific Criteria:

• Must have histologically confirmed CD20+ DLBCL at most recent (previous or current) representative tumor biopsy based on the pathology report, inclusive of the following according to the World Health Organization (WHO) 2016 (or later) classification.

• DLBCL, not otherwise specified (NOS) including de novo or histologically transformed from an earlier diagnosis of indolent lymphoma such as FL and nodal marginal zone lymphoma with a subsequent development of DLBCL relapse or.

• "Double-hit" or "triple-hit" with DLBCL morphology (technically classified in WHO 2016 as HGBCL, with MYC and BCL2 and/or BCL6 translocations). Note: Double- /triple-hit lymphomas without DLBCL morphology and those classified in WHO 2016 as HGBCL, NOS are not eligible.

• FL Grade 3B.

• Following safety run-in and up to the 12th participant (including the number of safety run-in participants) in Cohort 1, participants must have received at least 1 prior line of systemic therapies which must include an anti-CD20 monoclonal antibody containing combination therapy (e.g., rituximab). After safety run-in confirms tolerability of the full dose A of epcoritamab, participants must have received at least 2 prior lines of systemic therapies.

• Must have either failed prior autologous HSCT, or be ineligible for autologous HSCT due to age, comorbidities, performance status, comorbidities, or insufficient response to prior treatment.

• Must have relapsed or refractory disease. Note: Relapsed disease is defined as disease that has recurred >= 6 months after completion of therapy. Refractory disease is defined as disease that either progressed or failed to achieve an objective response during therapy or progressed within 6 months (< 6 months) of completion of therapy.

Cohort 2 Specific Criteria:

• Must have newly diagnosed CD20+ DLBCL.

• Must have one of the following histologically confirmed CD20+ DLBCL (de novo or histologically transformed from FL at most recent (previous or current) representative tumor biopsy based on the pathology report including one of the following diagnoses according to the WHO 2016 (or later) classification:

• DLBCL, not otherwise specified (NOS);

• "Double-hit" or "triple-hit" with DLBCL morphology (technically classified in WHO 2016 as HGBCL, with MYC and BCL2 and/or BCL6 translocations) Note: Double-/triple-hit lymphomas without DLBCL morphology and those classified in WHO 2016 as HGBCL, NOS are not eligible or;

• FL Grade 3B

• Eligible for standard R-CHOP for 6 cycles.

Cohort 3 Specific Criteria:

• Must have histologically confirmed CD20+ Grade 1 - 3a Follicular Lymphoma stage II, III, or IV with no evidence of histologic transformation to an aggressive lymphoma at most recent (previous or current) representative tumor biopsy and based on the pathology report, according to the WHO 2016 (or later) classification.

• Must have R/R disease to at least one prior systemic anti-lymphoma treatment which must include an anti CD20 monoclonal antibody (e.g., rituximab). Participant who received only prior anti-CD20 monoclonal antibody monotherapy is not eligible. Note: Relapsed disease is defined as disease that previously responded to therapy but progressed >= 6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy, failed to achieve an objective response or progressed within 6 months (< 6 months) of completion of therapy.

• Must be eligible for R2 per investigator determination.

• Willing to take aspirin prophylaxis (participants with low or intermediate risk for thromboembolism) or prophylactic anticoagulant (if high risk for a thromboembolic event) (lenalidomide treated participants only).

Exclusion Criteria:

All Cohorts:

• History of primary mediastinal lymphoma.

• Autologous Stem Cell Transplantation within 100 days prior to enrollment.

• Have received prior allogeneic hematopoietic stem cell transplantation at any time.

• Have been treated with a bispecific antibody targeting CD3 and CD20.

Cohort 2 Specific Criteria:

• History of prior systemic anti-lymphoma therapy (including definitive radiotherapy) for Diffuse large B-cell lymphoma (DLBCL) other than corticosteroids.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Epcoritamab
Subcutaneous Injection (SC)
• Cyclophosphamide
IV Injection
• Rituximab
Intravenous (IV) Infusion
• Doxorubicin
IV Infusion
• Vincristine
IV Infusion
• Prednisone
Oral; Tablet
• Lenalidomide
Oral; Capsule

Locations

Country	Name	City	State
China	Peking University Third Hospital /ID# 228138	Beijing	Beijing
China	The Fifth Medical Center of PLA General Hospital /ID# 230520	Beijing	Beijing
China	Hunan Cancer Hospital /ID# 231859	Changsha	Hunan
China	West China Hospital, Sichuan University /ID# 231434	Chengdu	Sichuan
China	Fujian Medical University Union Hospital /ID# 231890	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital /ID# 228028	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University /ID# 227916	Guangzhou	Guangdong
China	Sun Yat-Sen University Cancer Center /ID# 228033	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 228154	Hangzhou	Zhejiang
China	Zhejiang Cancer hospital /ID# 228776	Hangzhou	Zhejiang
China	Jiangxi Provincial Cancer Hospital /ID# 231944	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University /ID# 228771	Nanchang	Jiangxi
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 227724	Shanghai	Shanghai
China	The First Affiliated Hospital of Soochow University /ID# 228024	Suzhou	Jiangsu
China	Tianjin Cancer Hospital /ID# 228135	Tianjin	Tianjin
China	Union Hospital affiliated to Tongji Medical College of Huazhong University of Sc /ID# 231221	Wuhan	Hubei
China	The Affiliated Hospital of Xuzhou Medical College /ID# 228774	Xuzhou	Jiangsu
China	Henan Cancer Hospital /ID# 228772	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	AbbVie

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1 Part 2 [(3L+) R/R DLBCL]: Best Overall Response (BOR)	Best overall response (BOR) is defined as the percentage of participants in Cohort 1 Part 2 third line plus (3L) R/R DLBCL who achieved best overall response of complete response (CR) or partial response (PR) by Lugano 2014 criteria as assessed by independent review committee (IRC).	Up to Approximately 5 Years
Primary	Cohort 1 Part 1, Cohort 2, and Cohort 3: Number of Incidence of 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	Cohort 1 Part 2 [(3L+) R/R DLBCL]: Percentage of Participants with Complete Remission (CR)	CR is defined as the absence of lymphoma determined by Lugano 2014 criteria as assessed by IRC.	Up to Approximately 5 Years
Secondary	Cohort 1 Part 2 [(3L+) R/R DLBCL]: 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 radiographic progression determined by Lugano 2014 criteria as assessed by IRC, or death from any cause.	Up to Approximately 5 Years
Secondary	Cohort 1 Part 2 [(3L+) R/R DLBCL]: Overall survival (OS)	OS is defined for Cohort 1 epcoritamab monotherapy participants, as the time in months from first dose of epcoritamab to death from any cause.	Up to Approximately 5 Years
Secondary	Cohort 1 Part 2 [(3L+) R/R DLBCL]: Duration of response (DOR)	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 IRC, or death from any cause.	Up to Approximately 5 Years
Secondary	Cohort 1 Part 2 [(3L+) R/R DLBCL]: 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 IRC.	Up to Approximately 5 Years