A trial to learn if AZD0486 alone or with other anticancer drugs is safe and works in adults with certain blood cancers

Prior treatment

• All sub- studies: Major Surgical procedure within 14 days before the first dose of study drug
• 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, 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

Other illness

• All sub- studies: Clinically significant CV disease
• 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

Other

• All sub- studies: CNS lymphoma
• Sub-study 3: Cumulative dose of anthracycline > 150 mg/m2
• Sub-study 1: CLL transformation to more aggressive lymphoma
• Sub-study 2 Exclusion Criteria Refer to Section 5.2 of the Master Protocol.
• Sub-study 3: Mediastinal grey-zone lymphoma, Burkitt, Richter’s transformation, primary effusion LBCL

• 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