A Phase I/II Open-Label Multi-Centre Master Protocol to Evaluate the Safety and Efficacy of AZD0486 Monotherapy or in Combination with Other Anticancer Agents in Participants with Mature B-Cell Malignancies Substudy 1: Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma Substudy 2: Mantle Cell Lymphoma Substudy 3: Large B-Cell Lymphoma
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase I-II
PATOLOGÍA
Leucemia linfática crónica y otros SLPC, Mieloma Múltiple y otras gammapatías, Terapia celular y T-CARs, Trombosis y Anticoagulantes, Linfoma Folicular, Linfoma
CENTRO INVESTIGADOR
H. Fundación Jiménez Díaz
INVESTIGADOR PRINCIPAL
Daniel Morillo Giles
CENTRO INVESTIGADOR
H.U. Ramón y Cajal
INVESTIGADOR PRINCIPAL
Javier López Jiménez
FECHA DE APERTURA
Enero, 2025
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
All sub- studies: Age 18 years
Sub- study 2, Cohort 2A and Cohort 2C: Relapsed or Progressed after 2 or more prior systemic therapy for MCL including BTKi
Sub-study 3A: Previously untreated LBCL by WHO 2022 classification of lymphoid neoplasms OR Relapsed or refractory B-cell NHL after at least 1 prior lines of systemic therapy, Histologically confirmed according to WHO 2022 classification (excluding some B-NHL subtypes)
Sub-study 3: LVEF >50%
Sub-study 3A: IPI 2-5 for participants with untreated LBCL diagnoses
Sub-study 3: At least 1 measurable site as per Lugano
Sub-study 1B: Contraception during treatment and until at least x days after the last dose of Surovatamig and until 2 days after the last dose of acalabrutinib, whichever is longer.
All sub- studies: ECOG performance status 0 to 2
Sub-study 3: Contraception until x days after the last dose of surovatamig, 4 months after the last dose of vincristine, and 6 months after the last dose of cyclophosphamide or doxorubicin, (or as required by local prescribing information) whichever is longer.
All sub-studies: Contraception during treatment and at least x days after final dose
All sub- studies: Confirmed CD19 expression if prior anti-CD19 therapy
Sub-study 1, Cohort 1A and Cohort 1C: at least 2 prior lines of systemic therapy for CLL/SLL including treatment with a BTKi and BCL2i
Sub-study 1: CLL/SLL diagnosis and meets iwCLL criteria for treatment
Sub-study 1: SLL: at least 1 measurable site per Lugano
Sub-study 1: Absolute lymphocytes <25,000 cells/mcl
Sub study 3B: Histologically confirmed diagnosis of previously untreated LBCL by WHO 2022 classification of lymphoid neoplasms
Sub study 3B: For all participants: IPI score of 2 to 5.
Sub-study 3: Participant must be no older than 79 years of age at the time of signing ICF
Sub-study 1, Cohort 1B: at least 1 prior line of therapy and BTKi sensitive
Sub-study 2: MCL diagnosis per WHO
Sub-study 3: Absolute lymphocytes count of < 5 × 109 cells/L
Sub-study 3: Haemoglobin 9 g/dL
Sub-study 2: Clinical Stage II, III, or IV per Ann Arbor classification
Sub-study 2: At least 1 measurable site per Lugano
Sub-study 2: ALC < 25,000 cells/mcL
Sub- study 2, Cohort 2A and Cohort 2C: Relapsed or Progressed after 2 or more prior systemic therapy for MCL including BTKi
Sub-study 3A: Previously untreated LBCL by WHO 2022 classification of lymphoid neoplasms OR Relapsed or refractory B-cell NHL after at least 1 prior lines of systemic therapy, Histologically confirmed according to WHO 2022 classification (excluding some B-NHL subtypes)
Sub-study 3: LVEF >50%
Sub-study 3A: IPI 2-5 for participants with untreated LBCL diagnoses
Sub-study 3: At least 1 measurable site as per Lugano
Sub-study 1B: Contraception during treatment and until at least x days after the last dose of Surovatamig and until 2 days after the last dose of acalabrutinib, whichever is longer.
All sub- studies: ECOG performance status 0 to 2
Sub-study 3: Contraception until x days after the last dose of surovatamig, 4 months after the last dose of vincristine, and 6 months after the last dose of cyclophosphamide or doxorubicin, (or as required by local prescribing information) whichever is longer.
All sub-studies: Contraception during treatment and at least x days after final dose
All sub- studies: Confirmed CD19 expression if prior anti-CD19 therapy
Sub-study 1, Cohort 1A and Cohort 1C: at least 2 prior lines of systemic therapy for CLL/SLL including treatment with a BTKi and BCL2i
Sub-study 1: CLL/SLL diagnosis and meets iwCLL criteria for treatment
Sub-study 1: SLL: at least 1 measurable site per Lugano
Sub-study 1: Absolute lymphocytes <25,000 cells/mcl
Sub study 3B: Histologically confirmed diagnosis of previously untreated LBCL by WHO 2022 classification of lymphoid neoplasms
Sub study 3B: For all participants: IPI score of 2 to 5.
Sub-study 3: Participant must be no older than 79 years of age at the time of signing ICF
Sub-study 1, Cohort 1B: at least 1 prior line of therapy and BTKi sensitive
Sub-study 2: MCL diagnosis per WHO
Sub-study 3: Absolute lymphocytes count of < 5 × 109 cells/L
Sub-study 3: Haemoglobin 9 g/dL
Sub-study 2: Clinical Stage II, III, or IV per Ann Arbor classification
Sub-study 2: At least 1 measurable site per Lugano
Sub-study 2: ALC < 25,000 cells/mcL
CRITERIOS DE EXCLUSIÓN
All sub- studies: CNS lymphoma
Sub-study 3: Cumulative dose of anthracycline > 150 mg/m2
All sub- studies: Major Surgical procedure within 14 days before the first dose of study drug
All sub- studies: Clinically significant CV disease
All sub- studies: Unresolved non-haematological Grade 2 AEs (NCI CTCAE V5.0) from prior anticancer therapy (except alopecia or fatigue)
All sub-studies: Any anticancer systemic therapy within 5 half-lives or 21 days (whichever is shorter) prior to Cycle 1 Day 1
Prior allogenic HSCT or solid organ transplantation within 24 weeks of starting Cycle 1 Day 1
All sub-studies: Radiation therapy within 28 days of Cycle 1 Day 1
All sub-studies: Prior CAR-T therapy or auto-HSCT within 12 weeks or prior TCE within 8 weeks of Cycle 1 Day 1
All sub-studies: Prior Grade 3 CRS or ICANS event
Sub-study 1: CLL transformation to more aggressive lymphoma
All sub-studies: Active, significant, or uncontrolled infection or autoimmune disease requiring systemic therapy which places participant at unacceptable risk if he/she were to participate in the study
Sub-study 1, Cohort 1B: bleeding diathesis, treatment with strong CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist
Sub-study 2 Exclusion Criteria Refer to Section 5.2 of the Master Protocol.
Sub-study 3: Mediastinal grey-zone lymphoma, Burkitt, Richters transformation, primary effusion LBCL
Sub-study 3: Cumulative dose of anthracycline > 150 mg/m2
All sub- studies: Major Surgical procedure within 14 days before the first dose of study drug
All sub- studies: Clinically significant CV disease
All sub- studies: Unresolved non-haematological Grade 2 AEs (NCI CTCAE V5.0) from prior anticancer therapy (except alopecia or fatigue)
All sub-studies: Any anticancer systemic therapy within 5 half-lives or 21 days (whichever is shorter) prior to Cycle 1 Day 1
Prior allogenic HSCT or solid organ transplantation within 24 weeks of starting Cycle 1 Day 1
All sub-studies: Radiation therapy within 28 days of Cycle 1 Day 1
All sub-studies: Prior CAR-T therapy or auto-HSCT within 12 weeks or prior TCE within 8 weeks of Cycle 1 Day 1
All sub-studies: Prior Grade 3 CRS or ICANS event
Sub-study 1: CLL transformation to more aggressive lymphoma
All sub-studies: Active, significant, or uncontrolled infection or autoimmune disease requiring systemic therapy which places participant at unacceptable risk if he/she were to participate in the study
Sub-study 1, Cohort 1B: bleeding diathesis, treatment with strong CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist
Sub-study 2 Exclusion Criteria Refer to Section 5.2 of the Master Protocol.
Sub-study 3: Mediastinal grey-zone lymphoma, Burkitt, Richters transformation, primary effusion LBCL
DESCRIPCIÓN
To assess safety and tolerability and determine the RP2D (recommended Phase II dose) of surovatamig (administered as IV or SC) as monotherapy and in combination with other anticancer agents across mature B-cell malignancies
PALABRAS CLAVE
antagonistas de la vitamin k, bispecific antibody, cd19, gammapatia monoclonal, lymphocytic, lymphoma, mantle cell lymphoma, monoclonal gammopathy, small lymphocytic lymphoma, vitamin k antagonist
