Diffuse Large B-cell Lymphoma (DLBCL) MedDRA version: 21.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: zilovertamab vedotin
Product Code: [MK-2140]
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: Zilovertamab vedotin
CAS Number: 2376463-48-6
Current Sponso
Sponsors
MERCK SHARP & DOHME LLC. UNA SUSSIDIARIA DI MERCK & CO. INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of DLBCL, by prior biopsy, according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues, which includes but is not limited to: DLBCL, NOS germinal center B-cell type, or activated B-cell type; DLBCL leg-type; EBV+ DLBCL, NOS; and T cell histiocytic-rich DLBCL. DLBCL with overexpression of MYC, BCL2, and/or BCL6 proteins without rearrangement are also classified as DLBCL. DLBCL (HGBL) with MYC, BCL2, and/or BCL6 rearrangement will also be included. 2. Has PET-positive disease verified by BICR at Screening, defined as 4-5 on the Lugano 5-point scale. 3. Has received no prior treatment for their DLBCL. 4. Is male or female, >=18 years old at the time of providing documented informed consent. 5. If male, agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: - Zilovertamab vedotin: 110 days - Cyclophosphamide: 90 days - Doxorubicin: 90 days - Rituximab or rituximab biosimilar (truxima): no contraception needed • Refrains from donating sperm PLUS either: • Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR • Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below: - Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed. 6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Not a WOCBP OR • A WOCBP and: - Uses a contraceptive method that is highly effective (with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Has a history of transformation of indolent disease to DLBCL. 2. Has received solid organ transplant at any time. 3. Has received a diagnosis of PMBCL. 4. Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (=II), or serious cardiac arrhythmia requiring medication. 5. Has pericardial effusion or clinically significant pleural effusion. 6. Has ongoing Grade >1 peripheral neuropathy. 7. Has a demyelinating form of Charcot-Marie-Tooth disease. 8. History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. 9. Has contraindication to any of the study intervention components. 10. Has received prior radiotherapy within 28 days of start of study intervention. Participants must have recovered from all radiation-related toxicities. 11. Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 28 days prior to C1D1. 12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. 13. Has received a strong inhibitor or inducer of CYP3A4 (including itraconazole, ketoconazole, posaconazole, or voriconazole) within 7 days prior to C1D1 or expected requirement for chronic use of a strong CYP3A4 inhibitor or inducer during Cycle 1 of study therapy. 14. 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. 15. Has known active CNS lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission. 16. Has an active infection requiring systemic therapy. 17. Has a known history of HIV infection. 18. Has a known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 19. Has a known active hepatitis B infection defined as positive HBsAg and negative HBcAb or detectable HBV DNA by PCR testing. 20. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator. 21. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: 1. 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. 2. 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.;Primary end point(s): 1. Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) in Cycle 1 2. Number of Participants Who Experienced At Least One Adverse Event (AE) 3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) 4. Complete Response Rate (CRR) per Lugano Response Criteria;Timepoint(s) of evaluation of this end point: 1. Cycle 1 (up to 21 days) 2. Up to approximately 42 months 3. Up to approximately 5.5 months 4. Up to approximately 42 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective Response Rate (ORR) per Lugano Response Criteria 2. Duration of Response (DOR) per Lugano Response Criteria;Timepoint(s) of evaluation of this end point: 1. Up to approximately 42 months 2. Up to approximately 42 months | — |
Countries
Canada, Israel, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Turkey
Contacts
Public ContactDivisione Ricerca Clinica
MSD Italia Srl
Outcome results
None listed