Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

T-cell/histiocyte Rich Large B Cell Lymphoma

Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met

R-GemOx will be administrated in Cycles of 28 days until maximum cycles completion or any of the discontinuation criteria is met

BR will be administrated in Cycles of 21 days until maximum cycles completion or any of the discontinuation criteria is met

Following mandatory pre-medication subject will be administered epcoritamab as a subcutaneous injection.

Epcoritamab

Following mandatory pre-medication subject will be administered intravenously either BR or R-GemOx.

Investigator's Choice Chemotherapy

The drug that will be investigated in the study is an antibody, epcoritamab, also known as EPKINLY™ and GEN3013. Since the safety and tolerability of epcoritamab has already been studied in previous studies in humans, the main purpose of this study is to evaluate efficacy. To evaluate this, half of the participants who are eligible will receive epcoritamab and the other half will receive a pre-specified investigator's choice of chemotherapy. Epcoritamab will be studied in R/R DLBCL participants who did not respond to a previous autologous stem cell transplant (ASCT) or do not meet the criteria for ASCT

The trial is an open label, multi-center, global phase 3 randomized trial of epcoritamab, GEN3013. The goal of this randomized trial is to evaluate the efficacy of epcoritamab (GEN3013, DuoBody®-CD3xCD20) compared to investigator's choice of chemotherapy, in patients with relapsed, refractory diffuse large B-Cell Lymphoma who have failed or are ineligible for high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT). No change in chemotherapy is permitted for participants during the treatment phase of the trial.

A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL

A Randomized, Open-Label, Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)

OS is calculated as the time from first dose to death date or last date known to be alive.

PFS is calculated as the time from randomization to the date of disease progression or death, whichever is earlier. Progression is determined by the Lugano criteria and LYRIC.

ORR is calculated as the proportion of subjects achieving a complete response or partial response. Response is determined by the Lugano criteria and LYRIC.

CR rate is calculated as the proportion of subjects achieving a complete response. Response is determined by the Lugano criteria and LYRIC.

DOR is calculated as the time from initial response (CR or PR) to date of progression or death, whichever is earlier. Response and progression are determined by the Lugano criteria and LYRIC.

TTR is calculated as the time from randomization to date of initial response (CR or PR) among responders only. Response is determined by the Lugano criteria and LYRIC.

Compare other measures of efficacy to SOC - MRD negativity rate, defined as the proportion of subjects who have at least one negative MRD sample at any time point prior to start of subsequent anti-lymphoma therapy

TTNT is calculated as the time from randomization to date of initiation of new anti-lymphoma therapy.

identify patterns of incidence in adverse events, with particular emphasis on pre-defined adverse events of special interest

Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, immunoglobulins, and urinalyses

calculate incidence and present the occurrence of dose modifying toxicities by cycles and overall

calculate incidence of antibody response to epcoritamab in relation to dosing

monitor change from baseline in health-related quality of life over time and in relation to treatment

AbbVie

Genmab

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Blinatumomab

Dexamethasone

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Dexamethasone acetate

Etoposide phosphate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Blinatumomab was administered as a continuous intravenous (IV) infusion. Cycle 1 was 12 weeks (84 days) in duration with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, 112 µg/day for 6 weeks, followed by a 4-week treatment free time.

An optional 4-week Cycle 2 of blinatumomab was available for participants whose disease did not progress, with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, and 112 µg/day for 14 days.

There was a safety follow-up for 30 days. And a long-term follow-up of up to 8 months for a maximum of 1 year from first dose of blinatumomab or until participant death.

Blinatumomab monotherapy was supplied in single-use sterile glass injection vials and administered as an IV infusion.

During the run-in period participants received 6 cycles of standard of care rituximab-chemotherapy dosed per investigator's institution standard as follows:

* R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,prednisone)
* R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) or
* R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide).

Dexamethasone 20 mg IV: within 1 hour prior to start of treatment in each treatment cycle, and within 1 hour prior to dose-step (increase).

A phase 2, multicenter, open-label, single arm clinical trial in adults with newly diagnosed aggressive high-risk DLBCL.

The safety profile of blinatumomab after frontline rituximab (R)-chemotherapy, consisting of either R-CHOP (14 or 21) (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) or R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), or R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide), will be determined. The study will consist of a screening period of up to 14 days, a standard of care (SOC) R-chemotherapy run-in period of approximately 21 weeks, a 12 to 16 week blinatumomab treatment period, a 30-day safety follow-up visit, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose blinatumomab.

Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma

20150288 A Phase 2 Open-label Study Investigating the Safety and Efficacy of Blinatumomab After Frontline R-Chemotherapy in Adult Subjects With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma (DLBCL)

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Overall incidence and severity of treatment-emergent adverse events occurring during the blinatumomab investigative product (IP) treatment period graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale:

Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death.

Overall incidence and severity of treatment-emergent adverse events deemed by investigators to be related to blinatumomab treatment. Severity was graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale:

Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death.

Tumor response assessment was performed by a central reader according to modified Lugano classification using PET/CT scan. Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete metabolic response (CMR) or partial metabolic response (PMR). CMR: a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PMR: a score 4 (uptake moderately greater than \[\>\] liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline.

Duration of response was calculated only for responders during cycle 1. For participants who had CR or PR on the PET/CT scan at the end of the run-in period, response was measured from the start of blinatumomab treatment. For participants who had stable disease at the end of the run-in period, duration was calculated from documentation of the first assessment of either PR or CR on blinatumomab.

Progression was defined as the first diagnosis of progressive metabolic response/progressive disease based on PET/CT scan per central or investigator review during the treatment period or relapse based on clinical tumor assessment during the long-term follow up period.

Response duration was calculated until the start of new anti-tumor treatment (excluding any stem cell transplantation), PD, or death, whichever was the earliest event. Participants who did not have new anti-tumor treatment (excluding stem cell transplantation), PD, or death were censored at the last tumor assessment date.

Tumor response assessment was performed by a central reader according to modified Lugano classification using PET/CT scan.

CMR: a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology.

OS was calculated as the time from the date of first IP infusion until death due to any cause. Participants who are alive at the date that triggers the analysis were censored at the date last known to be alive.

Months were calculated as days from the first dose date of blinatumomab to death/censor date, divided by 30.5.

PFS was calculated as the time from the date of first IP infusion until the date of diagnosis of progression of DLBCL or the date of death, whichever was the earliest. The diagnosis of progression of DLBCL was defined as the first diagnosis of progressive metabolic response/progressive disease based on PET/CT scan per central or investigator review during the treatment period or relapse based on clinical tumor assessment during the long-term follow up period. Participants who were alive and did not have progression were censored at the last evaluable non-missing tumor assessment date prior to the analysis trigger date.

Percentage of participants who had HSCT during the Long Term Follow-Up Period.

The steady-state serum concentration (Css), summarized as the observed concentrations collected after at least 10 hours after the start of continuous IV infusion.

PK blood samples were analyzed in a central lab.

PK blood samples were analyzed in a central lab.

Amgen

All-cause mortality data are reported for all participants who enrolled in the Run-in Period. Adverse events are reported for all participants who received at least one dose of blinatumomab in the Treatment Period. During the long-term follow-up period, only serious adverse events related to blinatumomab were collected.

Age, Continuous

< 65 years

>=65 years

<75 years

>=75 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

* Stage I - Only one lymph node region is involved, only one lymph structure is involve
* Stage IE - Only one extranodal site (IE) is involved.
* Stage II - Two or more lymph node regions or lymph node structures on the same side of the diaphragm are involved.
* Stage III - Lymph node regions or structures on both sides of the diaphragm are involved.
* Stage IV - There is widespread involvement of a number of organs or tissues other than lymph node regions or structures, such as the liver, lung, or bone marrow.

Disease Stage at Time of Diagnosis

IPI score is an aid in predicting the prognosis of patients

* Low risk (0-1 points) - 5-year survival of 73%
* Low-intermediate risk (2 points) - 5-year survival of 51%
* High-intermediate risk (3 points) - 5-year survival of 43%
* High risk (4-5 points) - 5-year survival of 26%

International Prognostic Index Score at Diagnosis

The full analysis set included all participants who received at least 1 dose of blinatumomab.

Study Director

TEAE

TEAE severity grade >=3

TEAE severity grade >=4

Serious TEAE

TEAE leading to interruption of IP

Serious TEAE leading to interruption of IP

TEAE leading to discontinuation of IP

Serious TEAE leading to discontinuation of IP

Fatal TEAEs

Participants With Treatment-Emergent (Blinatumomab) Adverse Events

Treatment-related TEAE

Related TEAE severity grade >=3

Related TEAE severity grade >=4

Related Serious TEAE

Related TEAE leading to interruption of IP

Related Serious TEAE leading to interruption of IP

Related TEAE leading to discontinuation of IP

Related Serious TEAE leading to discon of IP

Related and Fatal TEAEs

Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment

Cycle 1

Entire Treatment Period

Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period

Responder Analysis Set includes all participants in the FAS that achieve objective response (CR or PR as per the Lugano classification) on the PET/CT scan.

Kaplan-Meier Estimates for Duration of Response

Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period

Kaplan-Meier Estimates for Overall Survival (OS) From First Dose of Blinatumomab

Kaplan-Meier Estimates for Progression Free Survival (PFS) From First Dose of Blinatumomab

Percentage of Participants Who Had Hematopoietic Stem Cell Transplantation (HSCT)

Cycle 1 Week 1: 9 mcg/day

Cycle 1 Week 2: 28 mcg/day

Cycle 1 Week 3: 112 mcg/day

Pharmacokinetic Analysis Set: participants who received any infusion of blinatumomab and had at least one PK sample collected

Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1

Pharmacokinetics (PK) Results for Blinatumomab: Clearance for Cycle 1

Pre-Study Run-In Period

Between Run-In and Treatment Periods

Treatment Period

Long Term Follow-Up Period

Digestive System Diseases

Symptoms and General Pathology

Colorectal Neoplasms

Microsatellite Instability

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Bone Density Conservation Agents

Vitamins

Antibodies

Antibodies, Monoclonal

Bevacizumab

Irinotecan

Cetuximab

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Calcium

Immunoglobulins

Calcium, Dietary

Folinic Acid

Subjects receive HX008 200 mg intravenous (IV) every 3 weeks (Q3W)

1. mFOLFOX6
2. mFOLFOX6+Bevacizumab
3. mFOLFOX6+Cetuximab
4. FOLFORI
5. FOLFORI+Bevacizumab
6. FOLFORI+Cetuximab

HX008

Drug: bevacizumab 5mg/kg given by IV every 14 days. Other Name: Avastin

Drug: cetuximab 400 mg/sqm initial dose, then 250 mg/sqm once weekly thereafter. Other Name: Erbitux

Drug: oxaliplatin 8 5 mg/sqm by IV, day1. Component of mFOLFOX6.

Drug: irinotecan 180 mg/sqm by IV, day1.Component of FOLFORI.

Drug: calcium Folinate 400 mg/sqm by IV, day1.Component of mFOLFOX6 or FOLFORI.

Drug: 5-fluorouracil 400 mg/sqm, day1,followed by 2400 mg/sqm iv infusion over 46\~48 h.Component of mFOLFOX6 or FOLFORI.

Jing Huang

Yifu He

Zhihui Liu

Yuxian Bai

Suxia Luo

Xinjun Liang

Xianli Yin

Qu Xiujuan, PhD

Hui Wang

Enxiao Li

The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), achieved by HX008 or Investigator's Choice Chemotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC).

A Study of HX008 Compared to Chemotherapy in the First-Line Treatment of Subjects With MSI-H/dMMR Metastatic Colorectal Cancer

A Randomized Phase III Study of HX008 (a Humanized Monoclonal Antibody Against PD-1) Compared to Investigator's Choice Chemotherapy in the First-Line Treatment of Subjects With Microsatellite Instability-High (MSI-H)/Deficient DNA Mismatch Repair (dMMR) Metastatic Colorectal Cancer

PFS, defined as the time from randomization to the first documented disease progression per RECIST 1.1 assessed by IRC or death due to any cause, whichever occurs first.

PFS, defined as the time from randomization to the first documented disease progression per RECIST 1.1 assessed by investigators or death due to any cause, whichever occurs first.

ORR, defined as the percentage of subjects achieving complete response (CR) and partial response (PR).

DCR, defined as the proportion of subjects achieving CR, PR, and Stable disease(SD) after treatment.

DOR, defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause.

OS, defined as the duration from the start of treatment to death of any cause.

iPFS, defined as the time from randomization to the first documented disease immune progression per iRECIST assessed by IRC/investigators or death due to any cause, whichever occurs first.

iORR, defined as the proportion of subjects with a best overall response (BOR) of immune complete response (iCR) or immune partial response (iPR) based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

response, a partial response or stable disease according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria by IRC/investigators over the the total number of evaluable patients.

iDOR, defined as the time from the date of the first immune response (iCR or iPR) to the date of immune confirmed progressive disease (iCPD) based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

ORR2, defined as proportion of subjects with best overall response of CR or PR, in progressors who continue to receive HX008 in crossover group.

DCR2, defined as the proportion of subjects achieving CR, PR, and SD after treatment who continue to receive HX008 in crossover group.

DOR2, defined as the duration from the initial recording received HX008 in crossover group of objective disease response to the second onset of tumor progression, or death of any cause.

PFS2, defined as duration of time until 2nd confirmed objective disease progression or death (or last documentation of being alive).

iORR2, defined as the proportion of subjects with a best overall response (BOR) of immune complete response (iCR) or immune partial response (iPR) in progressors who continue to receive HX008 in crossover group based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

iDCR 2, defined as the percentage of patients whose best overall response is either a complete response, a partial response or stable disease who continue to receive HX008 in crossover group according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria by IRC/investigators over the the total number of evaluable patients.

iDOR2, defined as the time from the date of the first immune response (iCR or iPR) to the date of immune confirmed progressive disease (iCPD) who continue to receive HX008 in crossover group based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

iPFS2, defined as duration of time until 2nd confirmed objective disease progression or death (or last documentation of being alive) who continue to receive HX008 in crossover group based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, etc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL	NCT04628494	Diffuse Large B...	Epcoritamab Investigator's ...	18 Years -	Genmab
Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma	NCT03023878	High-risk Diffu...	Blinatumomab Investigator's ... Dexamethasone	18 Years - 100 Years	Amgen
A Study of HX008 Compared to Chemotherapy in the First-Line Treatment of Subjects With MSI-H/dMMR Metastatic Colorectal Cancer	NCT05652894	Metastatic Colo...	HX008 Investigator's ...	18 Years -	Taizhou Hanzhong biomedical co. LTD

Spots Global Cancer Trial Database for investigator's choice chemotherapy