Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
50
Countries
3
Sites
12
Diffuse large B-cell lymphoma (DLBCL)
1. To evaluate the safety and tolerability and to establish a RP2D of zilovertamab vedotin when used in combination with R-CHP. 2. To evaluate zilovertamab vedotin at the RP2D in combination with R-CHP with respect to complete response rate per Lugano response as assessed by the investigator.
Key facts
- Sponsor
- Merck Sharp & Dohme LLC
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 10 Aug 2022 → ongoing
- Decision date (initial)
- 2023-04-03
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Merck Sharp & Dohme LLC
External identifiers
- EU CT number
- 2022-501380-40-00
- EudraCT number
- 2021-005861-41
- WHO UTN
- U1111-1280-2348
- ClinicalTrials.gov
- NCT05406401
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Pharmacogenomic, Safety, Therapy, Pharmacodynamic, Dose response, Pharmacogenetic, Efficacy
1. To evaluate the safety and tolerability and to establish a RP2D of zilovertamab vedotin when used in combination with R-CHP.
2. To evaluate zilovertamab vedotin at the RP2D in combination with R-CHP with respect to complete response rate per Lugano response as assessed by the investigator.
Secondary objectives 2
- To evaluate zilovertamab vedotin at the RP2D in combination with R-CHP with respect to ORR per Lugano response criteria as assessed by the investigator.
- To evaluate zilovertamab vedotin at the RP2D in combination with R-CHP with respect to DOR per Lugano response criteria as assessed by the investigator.
Conditions and MedDRA coding
Diffuse large B-cell lymphoma (DLBCL)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10012855 | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) | 10029104 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Dose Escalation Part 1 The dose escalation/confirmation phase is to determine the safety and tolerability and establish a preliminary recommended Phase 2 dose (RP2D) of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease.
|
Not Applicable | None | Different dose levels of zilovertamab vedotin + R-CHP: Zilovertamab dose levels are: • DL-1: 1.5 mg/kg • DL0: 1.75 mg/kg • DL1: 2.0 mg/kg • DL2: 2.25 mg/kg |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Has histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) by prior biopsy
- Has positron emission tomography (PET)-positive disease verified by blinded independent central review (BICR) at screening, defined as 4-5 on the Lugano response criteria 5-point scale
- Has received no prior treatment for DLBCL
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days prior to the start of study intervention
Exclusion criteria 18
- Has a history of transformation of indolent disease to DLBCL
- Has received solid organ transplant at any time
- Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL)
- Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication
- Has pericardial effusion or clinically significant pleural effusion
- Has ongoing Grade >1 peripheral neuropathy
- Has a demyelinating form of Charcot-Marie-Tooth disease
- History of a second malignancy unless potentially curative treatment has been completed with no evidence of malignancy for 2 years with the exception of participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous-cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder
- Has received prior radiotherapy within 28 days of start of study intervention
- Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent)
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- Has received a strong inhibitor or inducer of CYP3A4 (including itraconazole, ketoconazole, posaconazole, or voriconazole) within 7 days prior to the start of study intervention or expected requirement for chronic use of a strong CYP3A4 inhibitor until <30 days after the last dose
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days before the first dose of study intervention
- Has known active central nervous system (CNS) lymphoma
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known active hepatitis C virus infection
- Has a known active hepatitis B virus infection
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 4
- Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) in Cycle 1
- Number of Participants Who Experienced At Least One Adverse Event (AE)
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
- Complete Response Rate (CRR) per Lugano Response Criteria
Secondary endpoints 2
- Objective Response Rate (ORR) per Lugano Response Criteria
- Duration of Response (DOR) per Lugano Response Criteria
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 9
SUB06391MIG · Substance
- Active substance
- Doxorubicin
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 50 mg/m2 milligram(s)/sq. meter
- Max total dose
- 400 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 750 mg/m2 milligram(s)/sq. meter
- Max total dose
- 6000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12570MIG · Substance
- Active substance
- Rituximab
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 375 mg/m2 milligram(s)/sq. meter
- Max total dose
- 3000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Truxima 500 mg concentrate for solution for infusion
PRD4797328 · Product
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 375 mg/m2 milligram(s)/sq. meter
- Max total dose
- 3000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FA01 — -
- Marketing authorisation
- EU/1/16/1167/001
- MA holder
- CELLTRION HEALTHCARE HUNGARY KFT
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Betamethasone Sodium Phosphate
SCP881751 · ATC
- Active substance
- Betamethasone Sodium Phosphate
- Substance synonyms
- BETAMETHASONE DISODIUM PHOSPHATE
- Route of administration
- INTRAVENOUS
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 4000 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB06 — PREDNISOLONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Betamethasone Sodium Phosphate
SCP881751 · ATC
- Active substance
- Betamethasone Sodium Phosphate
- Substance synonyms
- BETAMETHASONE DISODIUM PHOSPHATE
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 4000 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB06 — PREDNISOLONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP132446 · ATC
- Active substance
- Prednisolone
- Substance synonyms
- (8S,9S,10S,11S,13S,14S,17R)-11,17-DIHYDROXY-17-(2-HYDROXYACETYL)-10,13-DIMETHYL-7,8,9,11,12,14,15,16-OCTAHYDRO-6H-CYCLOPENTA[A]PHENANTHREN-3-ONE, GLPG0303, DELTA-HYDROCORTISONE, 1,2-DEHYDROHYDROCORTISONE, METACORTANDRALONE
- Route of administration
- INTRAVENOUS
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 4000 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB07 — PREDNISONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP132446 · ATC
- Active substance
- Prednisolone
- Substance synonyms
- (8S,9S,10S,11S,13S,14S,17R)-11,17-DIHYDROXY-17-(2-HYDROXYACETYL)-10,13-DIMETHYL-7,8,9,11,12,14,15,16-OCTAHYDRO-6H-CYCLOPENTA[A]PHENANTHREN-3-ONE, GLPG0303, DELTA-HYDROCORTISONE, 1,2-DEHYDROHYDROCORTISONE, METACORTANDRALONE
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 4000 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB07 — PREDNISONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD9635968 · Product
- Active substance
- Zilovertamab Vedotin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 2.5 mg/kg milligram(s)/kilogram
- Max total dose
- 20 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- MERCK & CO. INC.
- Paediatric formulation
- No
- Orphan designation
- No
Auxiliary 1
-
L03A · Product
- Pharmaceutical form
- -
- Route of administration
- INTRAVENOUS
- Max daily dose
- 0 million IU million international units
- Max total dose
- 0 million IU million international units
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L03A — IMMUNOSTIMULANTS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Merck Sharp & Dohme LLC
- Sponsor organisation
- Merck Sharp & Dohme LLC
- Address
- 126 East Lincoln Avenue
- City
- Rahway
- Postcode
- 07065-4607
- Country
- United States
Scientific contact point
- Organisation
- Merck Sharp & Dohme LLC
- Contact name
- Puja Patel
Public contact point
- Organisation
- Merck Sharp & Dohme LLC
- Contact name
- Puja Patel
Third parties 5
| Organisation | City, country | Duties |
|---|---|---|
| Parexel International Corp. ORG-100007310
|
Auburndale, United States | Other |
| Almac Clinical Technologies LLC ORG-100043036
|
Souderton, United States | Interactive response technologies (IRT) |
| PPD International Holdings LLC ORG-100007655
|
Zaventem, Belgium | Laboratory analysis |
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Laboratory analysis |
| Bioclinica Inc. ORG-100033079
|
Princeton, United States | Other |
Locations
3 EU/EEA countries · 12 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruitment ended | 13 | 5 |
| Poland | Ongoing, recruitment ended | 8 | 4 |
| Spain | Ongoing, recruitment ended | 6 | 3 |
| Rest of world
Canada, Israel, Korea, Republic of, Turkey
|
— | 23 | — |
Investigational sites
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Istituto di ematologia, Largo Francesco Vito 1, 00168, Rome
Azienda Ospedaliera Nazionale Ss Antonio E Biagio E C Arrigo Alessandria
SCDU Ematologia, Via Venezia 16, 15121, Alexandria
Careggi University Hospital
SOD Ematologia, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
EMATOLOGIA I, Via Trabucco 180, 90146, Palermo
Ospedale San Raffaele S.r.l.
Unità Linfomi, Via Olgettina 60, 20132, Milan
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im.M.Kopernika W Lodzi
Oddział Hematologii Ogólnej, Ul. Pabianicka 62, 93-513, Lodz
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy
Klinika Nowotworów Układu Chłonnego, Ul. Wilhelma Konrada Roentgena 5, 02-781, Warsaw
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy
Oddział w Gliwicach Klinika Transplantacji Szpiku i Onkohematologii, Ul. Wybrzeze Armii Krajowej 15, 44-102, Gliwice
Uniwersyteckie Centrum Kliniczne
Klinika Hematologii i Transplantologii, Ul. Mariana Smoluchowskiego 17, 80-214, Gdansk
Hospital Universitario Fundacion Jimenez Diaz
Medical Oncology, Avenida De Los Reyes Catolicos 2, 28040, Madrid
Catalan Institute Of Oncology
Medical Oncology, Avinguda Gran Via De L'hospitalet 199-203, 08908, L'hospitalet De Llobregat
University Hospital Virgen Del Rocio S.L.
Medical Oncology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2022-09-22 | 2022-12-13 | 2024-08-05 | ||
| Poland | 2022-08-10 | 2022-08-11 | 2024-08-05 | ||
| Spain | 2022-08-24 | 2022-10-04 | 2024-08-05 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 31 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2022-501380-40-00_for pub | 03R |
| Recruitment arrangements (for publication) | K1_Recruit Arrangemt and IC Procedure_POL_Polish_for publication | 22APR2022 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_ESP_Spanish_for publication | 07MAR2022 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_ITA_EN_for pub | 04APR2023 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Study Card_ITA_IT_for pub | 31MAR2023 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_ESP_Spanish_for publication | 01 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_POL_PL_for pub | 01 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_ESP_ES_for pub | AM03v3.00R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_ITA_IT_for pub | AM03v3.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_POL_PL_for pub | 3.00R |
| Subject information and informed consent form (for publication) | L1_ICF_Optional tumor screening_ESP_Spanish_for publication | AM01v1.00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_data privacy_ITA_Italian_for publication | 29SEP2022 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_DILI sample_ITA_Italian_for publication | 29SEP2022 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_pregnant partner data privacy_ITA_IT_for pub | 17JUN2024 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_pregnant partner_ITA_IT_for pub | 30MAY2024 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_ITA_Italian_for publication | AM01v1-00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_tissue sample_POL_PL_for pub | 1.00R |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC RSI_DOXORUBICIN_Seacross Pharmaceuticals Ltd_SM10_for pub | 24JAN2025 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC RSI_Prednisone_for pub | 01MAR2022R |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC RSI_RITUXIMAB Roche Products Limited_SM05_for pub | 16JUL2024 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC RSI_TRUXIMA Celltrion Healthcare UK LTD_SM05_for pub | 13DEC2022 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC RSI_TRUXIMA Celltrion Healthcare UK LTD_SM10_for pub | 10JUN2025 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Q_RSI_PREDNISOLONE Amdipharm Mercury Co_SM05_for pub_Version 12Apr2024_12Apr2024 | 12APR2024 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC quality and RSI_Cyclophosphamide_Sandoz_for publication | 06APR2021 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501380-40_ESP_ES_ for pub | 3.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501380-40_ITA_IT_for pub | 3.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501380-40_POL_PL_for pub | 3.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501380-40-00_for pub | 3.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_ESP_ES_for pub | 01 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_ITA_IT_for publication | 01 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_POL_PL_for pub | 00 |
Application history
10 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-01-31 | Spain | Acceptable 2023-03-16
|
2023-03-17 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-04-18 | Spain | Acceptable 2023-06-12
|
2023-06-12 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-07-31 | Spain | Acceptable 2023-09-18
|
2023-09-18 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-06-12 | Spain | Acceptable 2024-08-12
|
2024-08-12 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-10-11 | Spain | Acceptable 2024-11-12
|
2024-11-13 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-03-06 | Spain | Acceptable 2025-04-10
|
2025-04-10 |
| 7 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-08-21 | Spain | Acceptable 2025-04-10
|
2025-08-21 |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-08-22 | Spain | Acceptable 2025-04-10
|
2025-08-22 |
| 9 | SUBSTANTIAL MODIFICATION | SM-9 | 2025-09-09 | Spain | Acceptable | 2025-09-25 |
| 10 | SUBSTANTIAL MODIFICATION | SM-10 | 2026-03-27 | Spain | Acceptable 2026-05-25
|
2026-05-26 |