CERTIS1Safety, Tolerability, and Preliminary Efficacy of AZD9574 in Advanced Solid Malignancies

AZD9574

AZD9574

AZD9574

Temozolomide (TMZ)

AZD9574

[11C]AZ1419 3391

AZD9574

Temozolomide (TMZ)

[11C]AZ1419 3391

AZD9574

[11C]AZ1419 3391

AZD9574

Trastuzumab Deruxtecan (T-DXd)

AZD9574

Trastuzumab Deruxtecan (T-DXd)

AZD9574

Datopotamab Deruxtecan (Dato-DXd)

Incidence of Adverse Events (AEs), and Serious Adverse Events (SAEs)

Changes from baseline in laboratory findings, electrocardiograms (ECGs), and vital signs

Change from baseline Eastern Cooperative Oncology Group performance status (ECOG PS)

Incidence of Dose Limiting Toxicities (DLTs)

Area Under the Curve (AUC)

Maximum plasma concentration (Cmax)

Time to reach maximum plasma concentration (tmax)

Minimum plasma concentration at steady state (Cmin,ss)

Half-life (t1/2)

Accumulation ratio

Dose proportionality

Module 1: Assessment of pH2AX (phospho-histone 2AX) (Ser139) PD biomarker modulations

Module 1: Percentage change in target lesion (TL) size

Module 1: Objective Response Rate (ORR)

Module 1: Duration of Response (DoR)

Module 1: Time To Response (TTR)

Module 1: Progression Free Survival (PFS)/radiographic Progression-Free Survival (rPFS)

Module 1: Cancer Antigen 125 (CA125) response evaluated according to the GCIG criteria (for ovarian patients only)

Module 1: Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result (for prostate cancer only)

Module 1: Radiological response evaluated according to RECIST v1.1 + Prostate Cancer Working Group 3 (PCWG3) response evaluation criteria (for prostate cancer only)

Module 2: Percentage change in TL size

Module 2: ORR

Module 2: DoR

Module 2: TTR

Module 2: PFS

Module 3: Occupancy

Module 3: Adverse Events (AEs) and Serious Adverse Events (SAEs)

Module 1 (Food effect): AUC

Module 1 (Food effect) : Area under the curve from 0 to t [AUC (0-t)]

Module 1 (Food effect): Cmax

Module 1 (Food effect): Tmax

Module 1 (Food effect) : Maximum plasma concentration (Cmax) ratio (with /without a high fat meal)

Module 1 (ARA effect): AUC

Module 1 (ARA effect): AUC (0-t)

Module 1 (ARA effect): Cmax

Module 1 (ARA effect): Tmax

Module 1 (ARA effect) : Cmax ratio (with /without famotidine)

Module 4 : Incidence of Adverse event of special interest (AESI)

Module 5 : Presence of positive ADAs for Dato-DXd

Module 5: ORR

Module 5: DoR

Module 5: TTR

Module 5: Progression Free Survival (PFS)/radiographic Progression-Free Survival (rPFS)

Module 5 : Incidence of AESIs

Module 3: AUC

Module 3: Cmax

Module 3: tmax

Module 3: Cmin,ss

Module 3: t1/2

Module 3: Accumulation ratio

Module 3: Percentage change in target lesion (TL) size

Module 3: ORR

Module 3: DoR

Module 3: TTR

Module 3: Progression Free Survival (PFS)/radiographic Progression-Free Survival (rPFS)

Module 3: Cancer Antigen 125 (CA125) response evaluated according to the GCIG criteria (for ovarian patients only)

Module 3: Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result (for prostate cancer only)

Module 3: Radiological response evaluated according to RECIST v1.1 + Prostate Cancer Working Group 3 (PCWG3) response evaluation criteria (for prostate cancer only)

Module 4: Cancer Antigen 125 (CA125) response evaluated according to the GCIG criteria (for ovarian patients only)

Module 5: Cancer Antigen 125 (CA125) response evaluated according to the GCIG criteria (for ovarian patients only)

Module 5: Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the post-baseline PSA result (for prostate cancer only)

Module 4 (Part B): Number of participants experiencing each level of symptomatic AEs as measured by the Patient-Reported Outcomes Version of the common terminology criteria for adverse events (PRO-CTCAE) (participants without brain metastases only)

Module 4 (Part B): Number of participants reporting overall side effect bother on the patient's global impression of treatment tolerability (PGI-TT) while receiving treatment (participants without brain metastases only)

Module 4 : AUC

Module 4 : Cmax

Module 4 : Tmax

Module 4 : Assessment of pH2AX (phospho-histone 2AX) (Ser139) PD biomarker modulations

Module 4 : Presence of ADAs for T-DXd

Module 4 (Part A): ORR

Module 4 (Part B): ORR

Module 4 (Part A): DoR

Module 4 (Part B): DoR

Module 4 (Part A): PFS

Module 4 (Part B): PFS

Module 4 (Part A): TTR

Module 4 (Part B): TTR

Module 4 (Part B only): Progression-free survival at 6 months (PFS6)

Module 5 : AUC

Module 5 : Cmax

Module 5 : Tmax

Module 5 : Assessment of pH2AX (phospho-histone 2AX) (Ser139) PD biomarker modulations