DATOPOTAMAB DERUXTECAN for Advanced or metastatic non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Participant ≥18 years old on the day of signing the ICF (local regulatory requirement to consent should be followed)\n- Histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC, without EGFR or ALK genomic alterations (not required for squamous histology) and no known genomic alterations in other actionable driver kinases with approved therapies (KRAS mutations eligible). Cohort 4a will enroll participants with squamous histology only; cohorts 5 Part 2A and Part 2B as well as Cohorts 12 and 13 will enroll participants with non-squamous histology only\n- For Cohorts 1 to 4, participants must be treatment-naïve or have received and radiologically progressed after only 1 prior line of systemic chemotherapy, without concomitant immune checkpoint inhibitors for advanced or metastatic NSCLC. Cohorts 4a, 5 to 11 and 14 participants must be treatment-naïve for advanced or metastatic NSCLC. For Cohorts 12 & 13, participants must be CPI-acquired resistant after 1 or 2 prior lines of systemic therapy for advanced or metastatic NSCLC, of which at least 1 prior line of therapy should contain an approved anti-PD-1/PD-L1\n- Willing and able to undergo a mandatory tumor biopsy. A tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen may be substituted for the biopsy collected during screening. For Cohorts 12 and 13, a tumor sample taken ≤24 months prior to screening is acceptable.\n- Has measurable disease per RECIST1.1 within 28 days prior to Cycle 1 Day 1\n- Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 at screening\n- Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 day 1\n- For Cohorts 5 to 14 only: Documented IHC PD-L1 expression per analytically validated Ventana PD-L1 (SP263) IHC assay, 22C3 PharmDx assay, or 28-8 PharmDx assay"}

Exclusion criteria

• {"criterion_text":"- Active or prior documented autoimmune or inflammatory disorders\n- Uncontrolled or significant cardiac disease\n- History of another primary malignancy with exceptions\n- active or uncontrolled hepatitis B or C virus or uncontrolled HIV infection\n- spinal cord compression or clinically active CNS metastases\n- History of (non-infectious) ILD/pneumonitis, including radiation pneumonitis, that required steroids\n- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illness\n- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals\n- Clinically significant corneal disease"}

Primary endpoints

• {"endpoint_text":"- Safety and tolerability of combination treatment with Dato-DXd and immunotherapy with or without up to 4 cycles of carboplatin, as measured by DLTs, TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings","definition_or_measurement_approach":"Measured by DLTs, TEAEs, SAEs, AESIs, ECOG performance status, vital signs, standard clinical laboratory parameters (hematology, clinical chemistry, urinalysis), ECG parameters, ECHO/MUGA findings, and ophthalmologic findings."}

Secondary endpoints

• {"endpoint_text":"- Efficacy of combination treatment with Dato-DXd and immunotherapy, with or without up to 4 cycles of carboplatin as measured by ORR, DoR, DCR, PFS, TTR, Best percentage change in the SoD of measurable tumors and OS","definition_or_measurement_approach":"Measured by ORR, DoR, DCR, PFS, TTR, best percentage change in sum of diameters (SoD) of measurable tumors, and overall survival (OS)."}
• {"endpoint_text":"- PK of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789, with or without up to 4 cycles of carboplatin as assessed by plasma concentrations and PK parameters of Dato-Dxd, total anti-TROP2 antibody and DXd (MAAA-1181a). Serum concentrations and PK parameters of durvalumab, AZD2936, MEDI5752 and AZD7789","definition_or_measurement_approach":"Assessed by plasma concentrations and PK parameters for Dato-DXd (including total anti-TROP2 antibody and DXd) and serum concentrations and PK parameters for durvalumab, AZD2936, MEDI5752 and AZD7789."}
• {"endpoint_text":"- Immunogenicity of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 with or without 4 cycles of carboplatin as assessed by the prevalence and incidence of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA.","definition_or_measurement_approach":"Assessed by prevalence and incidence of anti-drug antibodies (ADA) for Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789."}

Spain

Latest Decision Or Authorization Date

27-06-2024

Number Of Sites

7

Number Of Participants

31

Poland

Latest Decision Or Authorization Date

05-07-2024

Number Of Sites

4

Number Of Participants

19

Italy

Latest Decision Or Authorization Date

01-07-2024

Number Of Sites

3

Number Of Participants

15

Belgium

Latest Decision Or Authorization Date

25-06-2024

Number Of Sites

3

Number Of Participants

10

Primary sponsor

Full Name

Astrazeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden