Phase 1b Study of Dato-DXd in Combination with Immunotherapy with or without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer

Phase 1

Recruiting

• Conditions: Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC); MedDRA version: 21.1Level: PTClassification code: 10061873Term: Non-small cell lung cancer Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-505992-54-00
• Lead Sponsor: Astrazeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-15
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 232

Inclusion Criteria

Participant =18 years old on the day of signing the ICF (local regulatory requirement to consent should be followed), 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), 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. For Cohorts 5 to 11, 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 1 prior line of therapy should contain an approved anti-PD-1/PD-L1, Willing and able to undergo a mandatory tumor biopsy, Has measurable disease per RECIST1.1 within 28 days prior to Cycle 1 Day 1, Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 at screening, Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 day 1, 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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of combination treatment with Dato-DXd and immunotherapy, with or without up to 4 cycles of carboplatin;Secondary Objective: To assess the efficacy of combination treatment with Dato-DXd and immunotherapy, with or without up to 4 cycles of carboplatin, To evaluate the PK of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789, with or without up to 4 cycles of carboplatin, To assess the immunogenicity of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 with or without up to 4 cycles of carboplatin;Primary end point(s): 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

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):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;Secondary end point(s):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;Secondary end point(s):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.