TRASTUZUMAB DERUXTECAN for HER2-expressing tumors

Inclusion criteria

• {"criterion_text":"- Locally advanced, unresectable, or metastatic disease based on most recent imaging\n- Part 1: The respective cohorts for patient inclusion are: - Cohort 1: Biliary tract cancer - Cohort 2: Bladder cancer - Cohort 3: Cervical cancer - Cohort 4: Endometrial cancer - Cohort 5: Epithelial ovarian cancer - Cohort 6: Pancreatic cancer - Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer.\n- Part 2:The respective cohorts for patient inclusion are: - Cohort A: Metastatic or advanced solid tumors that are HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included. -Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+/ISH+ any tumor type (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included. -Cohort C: Metastatic or advanced solid endometrial cancer that is HER2 IHC 2+ or 1+. -Cohort D: Metastatic or advanced ovarian cancer that is HER2 IHC 2+ or 1+. -Cohort E: Metastatic or advanced solid cervical cancer that is HER2 IHC 2+ or 1+.\n- Progressed following prior treatment or who have no satisfactory alternative treatment option.\n- Prior HER2 targeting therapy is permitted.\n- HER2 expression scored using current ASCO/CAP guidelines for scoring HER2 for gastric cancer. -Part 1: IHC 3+ or IHC 2+ by local or central assessment -\tPart 2: IHC and ISH results by central assessment as pre-defined for each cohort\n- Has measurable target disease assessed by the Investigator based on RECIST version 1.1.\n- Has protocol-defined adequate organ function including cardiac, renal and hepatic function."}

Exclusion criteria

• {"criterion_text":"- History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening\n- Lung-specific intercurrent clinically significant severe illnesses\n- Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals\n- Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART\n- Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.\n- Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastroesophageal junction, or non-small cell lung cancer for Part 1. For Part 2, patients with primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction will be excluded.\n- Medical conditions that may interfere with the subject's participation in the study."}

Primary endpoints

• {"endpoint_text":"- Objective Response Rate (ORR) according to RECIST v1.1, as assessed by investigator","definition_or_measurement_approach":"Objective Response Rate (ORR) according to RECIST v1.1, as assessed by investigator"}

Secondary endpoints

• {"endpoint_text":"- Based on RECIST 1.1, as assessed by Investigator: 1) Duration of response (DoR).","definition_or_measurement_approach":"Based on RECIST 1.1, as assessed by Investigator"}
• {"endpoint_text":"- Disease control rate (DCR).","definition_or_measurement_approach":"Disease control rate as defined in protocol (DCR)"}
• {"endpoint_text":"- Progression free survival (PFS).","definition_or_measurement_approach":"Progression-free survival (PFS) per protocol"}
• {"endpoint_text":"- Proportion of patients alive and progression-free at 3 monthly intervals staring from 6 months.","definition_or_measurement_approach":"Proportion alive and progression-free assessed at 3-month intervals starting from 6 months"}
• {"endpoint_text":"- Overall survival (OS).","definition_or_measurement_approach":"Overall survival (OS) as time from first dose to death from any cause"}
• {"endpoint_text":"- Proportion of patients alive at 3 monthly intervals staring from 6 months","definition_or_measurement_approach":"Proportion alive assessed at 3-month intervals starting from 6 months"}
• {"endpoint_text":"- Occurrence of adverse events (AEs) and serious adverse events (SAEs).","definition_or_measurement_approach":"Incidence of AEs and SAEs collected throughout treatment and follow-up per protocol safety reporting"}
• {"endpoint_text":"- Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181.","definition_or_measurement_approach":"Serum concentration measurements of T-DXd, total anti-HER2 antibody and MAAA-1181 per PK sampling schedule"}
• {"endpoint_text":"- The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd.","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADAs) for T-DXd per immunogenicity testing schedule"}

Italy

Earliest CTIS Part Ii Submission Date

17-05-2024

Latest Decision Or Authorization Date

27-01-2026

Processing Time Days

620

Number Of Sites

4

Number Of Participants

24

Poland

Earliest CTIS Part Ii Submission Date

17-05-2024

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

623

Number Of Sites

5

Number Of Participants

40

Spain

Earliest CTIS Part Ii Submission Date

17-05-2024

Latest Decision Or Authorization Date

17-02-2026

Processing Time Days

641

Number Of Sites

4

Number Of Participants

46

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden