Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies

Required: BRCA1 predicted loss of function germline or tumour mutation

evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or RAD51D

Required: BRCA2 predicted loss of function germline or tumour mutation

evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or RAD51D

Required: PALB2 predicted loss of function germline or tumour mutation

evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or RAD51D

Required: RAD51C predicted loss of function germline or tumour mutation

evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or RAD51D

Required: RAD51D predicted loss of function germline or tumour mutation

evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or RAD51D

Required: IDH1 mutation

IDH1/2-mutant glioma

Required: IDH2 mutation

IDH1/2-mutant glioma

Required: HER2 (ERBB2) overexpression (IHC 3+ or IHC 2+/ISH-positive or IHC 2+/ISH-negative or IHC 1+) (IHC 3+ or IHC 2+/ISH-positive or IHC 2+/ISH-negative or IHC 1+)

Breast cancer must be IHC 3+ or IHC 2+/ISH-positive or IHC 2+/ISH-negative or IHC 1+ as determined by local testing using current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines for scoring HER2 + breast cancer.

Required: HER2 (ERBB2) overexpression (IHC 3+ or IHC 2+/ISH-positive) (IHC 3+ or IHC 2+/ISH-positive)

Gastric cancer should be IHC 3+ or IHC 2+/ISH-positive based on local tissue testing results.

Required: HER2 (ERBB2) overexpression (IHC 3+ or IHC 2+) (IHC 3+ or IHC 2+)

Participants with non-breast and non-gastric cancers must have HER2-overexpression (IHC 3+ or IHC 2+; as determined by local testing using current ASCO-CAP guidelines for gastric IHC scoring).

Required: HER2 (ERBB2) activating mutation

Participants with NSCLC will also be eligible based on the presence of a HER2activating mutation.

Cannot have received: PARP inhibitor

Exception: Module 1: > one prior line of therapy in any setting with a PARPi-based regimen; Module 2: received a PARPi previously; Module 3 Panel 1/2/3: > one prior line of therapy in any setting with a PARPi-based regimen; Module 5: prior treatment with PARPi is permitted

Have received > one prior line of therapy in any setting with a PARPi-based regimen; Received a PARPi previously

Cannot have received: alkylating chemotherapy (procarbazine, lomustine (CCNU), vincristine (PCV))

Have received > 1 prior line of alkylating chemotherapy regimen. Participants who have received procarbazine, lomustine (CCNU), vincristine (PCV) as a prior line of treatment are not allowed.

Cannot have received: bevacizumab (bevacizumab)

Exception: within the last 6 months

Received bevacizumab within the last 6 months.

Cannot have received: HER2 directed TOPO1i ADCs

Prior treatment with HER2 directed TOPO1i ADCs and prior AZD9574 is not permitted.

Cannot have received: TROP2-directed ADCs

Prior treatment with TROP2-directed ADCs is NOT permitted.

Cannot have received: TOPO1 inhibitor

Prior TOPO1 inhibitor therapy is NOT permitted