Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

NCT ID: NCT04663347

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

543 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-03

Study Completion Date

2027-09-30

Brief Summary

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The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating participants with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied.

Trial details include:

* The treatment duration for each participant depends upon which arm of treatment they are assigned to.
* The visit frequency for each participant depends upon which arm of treatment they are assigned to, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks.
* All participants will receive active drug; no one will be given placebo.

Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned.

Participants who receive standard treatments will have intravenous (IV) infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned.

Detailed Description

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A Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard of care (SOC) agents in participants with B-NHL.

All participants in the trial will receive epcoritamab, as monotherapy or in combination. The following regimens will be investigated:

* Arm 1: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated diffuse large B-cell lymphoma (DLBCL)
* Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL)
* Arm 3: epcoritamab + rituximab and bendamustine (BR) in participants with previously untreated FL
* Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in participants with R/R DLBCL eligible for autologous stem cell transplant (ASCT)
* Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity
* Arm 6: epcoritamab + R2 in participants with previously untreated FL
* Arm 7: epcoritamab maintenance in participants with FL who achieve a complete response (CR) or a partial response (PR) following first or second line SOC treatment
* Arm 8: epcoritamab + reduced dose of R-CHOP (R mini-CHOP) in participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline
* Arm 9: epcoritamab + lenalidomide for second-line treatment in participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy
* Arm 10: epcoritamab + rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) in participants with R/R DLBCL eligible for ASCT

The trial consists of two parts: Part 1 ('Dose Escalation') and Part 2 ('Dose Expansion'). The primary objective of Part 1 is safety, and it includes Arm 1-5 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Participants in Arm 1-5 and Arm 10 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities (DLTs) will be assessed in Part 1 and for a selected number of participants in Arm 8 during a 28-day period (safety run-in). The arms are conducted in parallel.

Conditions

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Diffuse Large B-Cell Lymphoma Follicular Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1 - Epcoritamab + R-CHOP

In participants with previously untreated DLBCL.

Group Type EXPERIMENTAL

rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

Intervention Type DRUG

6 cycles (21-day cycles)

Epcoritamab

Intervention Type BIOLOGICAL

Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.

Arm 2 - Epcoritamab + R2

In participants with R/R FL.

Group Type EXPERIMENTAL

Epcoritamab

Intervention Type BIOLOGICAL

Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules.

Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years.

In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.

Rituximab and Lenalidomide

Intervention Type DRUG

Rituximab 375 milligrams per meter squared (mg/m\^2) will be administered intravenously QW in Cycle 1 and Q4W in Cycles 2-5. Lenalidomide 20 mg will be administered orally daily for 21 days for 12 cycles.

Arm 3 - Epcoritamab + BR

In participants with previously untreated FL.

Group Type EXPERIMENTAL

rituximab and bendamustine

Intervention Type DRUG

6 cycles (28-day cycles)

Epcoritamab

Intervention Type BIOLOGICAL

Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.

Arm 4 - Epcoritamab + R-DHAX/C

In participants with R/R DLBCL eligible for ASCT.

Group Type EXPERIMENTAL

rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin

Intervention Type DRUG

3 cycles (21-day cycles)

Epcoritamab

Intervention Type BIOLOGICAL

Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.

Arm 5 - Epcoritamab + GemOx

In participants with R/R DLBCL ineligible ASCT.

Group Type EXPERIMENTAL

gemcitabine and oxaliplatin

Intervention Type DRUG

4 cycles (28-day cycles)

Epcoritamab

Intervention Type BIOLOGICAL

Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.

Arm 6 - Epcoritamab + R2

In participants with previously untreated FL.

Group Type EXPERIMENTAL

rituximab and lenalidomide

Intervention Type DRUG

rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)

Epcoritamab

Intervention Type BIOLOGICAL

Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.

Arm 7 - Epcoritamab maintenance

In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.

Group Type EXPERIMENTAL

Epcoritamab

Intervention Type BIOLOGICAL

Every week in cycle 1 and then every 8 weeks for a total of 2 years.

Arm 8 - Epcoritamab + R mini-CHOP

In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.

Group Type EXPERIMENTAL

rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone

Intervention Type DRUG

6 cycles (21-day cycles)

Epcoritamab

Intervention Type BIOLOGICAL

Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.

Arm 9 - Epcoritamab + Lenalidomide

In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.

Group Type EXPERIMENTAL

Lenalidomide

Intervention Type DRUG

12 cycles (28-day cycles)

Epcoritamab

Intervention Type BIOLOGICAL

Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.

Arm 10 - Epcoritamab + R-ICE

In participants with R/R DLBCL eligible for ASCT.

Group Type EXPERIMENTAL

rituximab, ifosfamide, carboplatin, and etoposide phosphate

Intervention Type DRUG

3 cycles (21-day cycles)

Epcoritamab

Intervention Type BIOLOGICAL

Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.

Interventions

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rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

6 cycles (21-day cycles)

Intervention Type DRUG

rituximab and lenalidomide

rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)

Intervention Type DRUG

rituximab and bendamustine

6 cycles (28-day cycles)

Intervention Type DRUG

rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin

3 cycles (21-day cycles)

Intervention Type DRUG

gemcitabine and oxaliplatin

4 cycles (28-day cycles)

Intervention Type DRUG

Epcoritamab

Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.

Intervention Type BIOLOGICAL

rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone

6 cycles (21-day cycles)

Intervention Type DRUG

Lenalidomide

12 cycles (28-day cycles)

Intervention Type DRUG

rituximab, ifosfamide, carboplatin, and etoposide phosphate

3 cycles (21-day cycles)

Intervention Type DRUG

Epcoritamab

Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.

Intervention Type BIOLOGICAL

Epcoritamab

Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.

Intervention Type BIOLOGICAL

Epcoritamab

Every week in cycle 1 and then every 8 weeks for a total of 2 years.

Intervention Type BIOLOGICAL

Epcoritamab

Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.

Intervention Type BIOLOGICAL

Epcoritamab

Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.

Intervention Type BIOLOGICAL

Epcoritamab

Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.

Intervention Type BIOLOGICAL

Epcoritamab

Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules.

Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years.

In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.

Intervention Type BIOLOGICAL

Rituximab and Lenalidomide

Rituximab 375 milligrams per meter squared (mg/m\^2) will be administered intravenously QW in Cycle 1 and Q4W in Cycles 2-5. Lenalidomide 20 mg will be administered orally daily for 21 days for 12 cycles.

Intervention Type DRUG

Epcoritamab

Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.

Intervention Type BIOLOGICAL

Other Intervention Names

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R-CHOP R2 BR R-DHAX/C GemOx GEN3013 DuoBody®-CD3xCD20 EPKINLY™ R mini-CHOP R-ICE GEN3013 DuoBody®-CD3xCD20 EPKINLY™ GEN3013 DuoBody®-CD3xCD20 EPKINLY™ GEN3013 DuoBody®-CD3xCD20 EPKINLY™ GEN3013 DuoBody®-CD3xCD20 EPKINLY™ GEN3013 DuoBody®-CD3xCD20 EPKINLY™ GEN3013 DuoBody®-CD3xCD20 EPKINLY™ GEN3013 DuoBody®-CD3xCD20 EPKINLY™ R2 GEN3013 DuoBody®-CD3xCD20 EPKINLY™

Eligibility Criteria

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Inclusion Criteria

1. Measurable disease defined as ≥1 measurable nodal lesion (long axis \>1.5 cm and short axis \>1.0 cm) or ≥1 measurable extra-nodal lesion (long axis \>1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI). Applies to all arms except arm 7.
2. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
3. Acceptable organ function at screening
4. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
5. If of childbearing potential participant must practicing a highly effective method of birth control
6. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control

Arm 1:

* Newly diagnosed DLBCL
* DLBCL, not otherwise specified (NOS)
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Arm 2: R/R FL

Arm 3: Newly diagnosed, previously untreated FL grade 1-3A

Arm 4:

* Documented R/R DLBCL and eligible for HDT-ASCT
* DLBCL, NOS
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Arm 5:

* Documented R/R DLBCL and ineligible for HDT-ASCT
* DLBCL, NOS
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Arm 6: Newly diagnosed, previously untreated FL grade 1-3A

Arm 7:

* FL Grade 1-3A
* If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment.

Arm 8:

* Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline
* T-cell/histiocyte rich DLBCL
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Arm 9:

* R/R FL
* Progressed within 24 months of initiating first-line treatment

Arm 10:

* Documented R/R DLBCL and eligible for HDT-ASCT
* DLBCL, NOS
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Exclusion Criteria

1. Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
2. Any prior treatment with a bispecific antibody targeting CD3 and CD20.
3. Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
4. Clinically significant cardiovascular disease
5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
6. CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
7. Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
8. Known history of seropositivity of human immunodeficiency virus (HIV)
9. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
10. Neuropathy \> grade 1
11. Receiving immunostimulatory agent
12. Prior allogeneic HSCT
13. Current seizure disorder requiring anti-epileptic therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genmab

INDUSTRY

Sponsor Role lead

AbbVie

INDUSTRY

Sponsor Role collaborator

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center Michigan Medicine

Ann Arbor, Michigan, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Mount Sinai

New York, New York, United States

Site Status

Memorial Sloan Kettering CC

New York, New York, United States

Site Status

Levine Cancer Center

Charlotte, North Carolina, United States

Site Status

Southwestern Medical Center

Dallas, Texas, United States

Site Status

Austin Health

Heidelberg, , Australia

Site Status

Linear Clinical Research Limited

Nedlands, , Australia

Site Status

AZ Sint-Jan

Bruges, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

CHU UCL Namur Site Godinne

Yvoir, , Belgium

Site Status

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Site Status

Fakultni nemocnice Ostrava

Ostrava - Poruba, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Vseobecna Fakultni Nemocnice

Prague, , Czechia

Site Status

Århus Hospital

Aarhus, , Denmark

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Vejle Sygehus

Vejle, , Denmark

Site Status

Kuopio University Hospital

Kuopio, , Finland

Site Status

HUS Cancer Center

Lahti, , Finland

Site Status

Hopital Claude Huriez - CHRU Lille

Lille, , France

Site Status

Hôpital de la Timone

Marseille, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

Bergamo, , Italy

Site Status

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, , Italy

Site Status

Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCS

Candiolo, , Italy

Site Status

IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST

Meldola, , Italy

Site Status

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia

Reggio Emilia, , Italy

Site Status

Amsterdam UMC, Locatie VUMC

Amsterdam, , Netherlands

Site Status

Universitair Medisch Centrum Groningen (UMCG)

Groningen, , Netherlands

Site Status

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Site Status

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Site Status

UMC Utrecht

Utrecht, , Netherlands

Site Status

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, , Norway

Site Status

ICO l Hospitalet

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Södra Älvsborgs Sjukhus

Borås, , Sweden

Site Status

Sahlgrenska Sjukhuset

Gothenburg, , Sweden

Site Status

Skånes Universitetssjukhus

Lund, , Sweden

Site Status

Karolinska Universitetssjukhuset

Solna, , Sweden

Site Status

Akademiska Sjukhuset

Uppsala, , Sweden

Site Status

The Christie Hospital

Manchester, , United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Derriford Hospital

Plymouth, , United Kingdom

Site Status

Countries

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United States Australia Belgium Czechia Denmark Finland France Italy Netherlands Norway Spain Sweden United Kingdom

References

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Falchi L, Sureda A, Leppa S, Vermaat JSP, Nijland M, Christensen JH, de Vos S, Holte H, Merryman RW, Lugtenburg PJ, Abrisqueta P, Linton KM, Sunkersett G, Hoehn D, Rana A, Abbas A, Marek J, Hao Y, Steele AJ, Morehouse C, Hutchings M, Belada D. Fixed-duration epcoritamab plus R2 drives favorable outcomes in relapsed or refractory follicular lymphoma. Blood. 2025 Nov 27;146(22):2629-2640. doi: 10.1182/blood.2025029909.

Reference Type DERIVED
PMID: 40920572 (View on PubMed)

Brody JD, Jorgensen J, Belada D, Costello R, Trneny M, Vitolo U, Lewis DJ, Karimi YH, Sureda A, Andre M, Wahlin BE, Lugtenburg PJ, Jiang T, Karagoz K, Steele AJ, Abbas A, Wang L, Risum M, Cordoba R. Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial. Blood. 2025 Apr 10;145(15):1621-1631. doi: 10.1182/blood.2024026830.

Reference Type DERIVED
PMID: 39792928 (View on PubMed)

Related Links

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https://fimea.fi/valvonta/kliiniset_laaketutkimukset/rekrytoivat-tutkimukset

Patient website: Recruiting clinical sites in Finland

Other Identifiers

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2023-504805-35-00

Identifier Type: CTIS

Identifier Source: secondary_id

2020-000845-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL74222.056.20

Identifier Type: REGISTRY

Identifier Source: secondary_id

283235

Identifier Type: OTHER

Identifier Source: secondary_id

RECF4377

Identifier Type: OTHER

Identifier Source: secondary_id

GCT3013-02

Identifier Type: -

Identifier Source: org_study_id

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