A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC
- Conditions
- Metastatic Non-Small Cell Lung Cancer (NSCLC)
- Interventions
- Registration Number
- NCT03819465
- Lead Sponsor
- AstraZeneca
- Brief Summary
This study is designed to determine the efficacy and safety of durvalumab and/or novel oncology therapies, with or without chemotherapy, for first-line Stage IV Non-Small Cell Lung Cancer (NSCLC)
- Detailed Description
This is a Phase IB, Open-Label, Multi-Center Study to Determine the Efficacy and Safety of Durvalumab and/or Novel Oncology Therapies, With or Without Chemotherapy, for First-Line Stage IV Non-Small Cell Lung Cancer (NSCLC).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 175
- Histologically or cytologically documented Stage IV NSCLC not amenable to curative surgery or radiation
- No prior chemotherapy or any other systemic therapy for metastatic NSCLC
- Prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for advanced disease are eligible, if progression has occurred >12 months from end of last therapy
- Known tumor PD-L1 status
- Tumors that lack activating EGFR mutations and ALK fusions or documented local test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care
- WHO/ECOG status at 0 or 1 at enrollment
- Life expectancy of at least 12 weeks
- Troponin I or T ≤ ULN (per institutional guidelines)
- Active or prior documented autoimmune or inflammatory disorders
- History of active primary immunodeficiency
- Any prior chemotherapy or any other systemic therapy for metastatic NSCLC
- Untreated CNS metastases
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description B2 Nab-paclitaxel Durvalumab + Investigator's choice of chemotherapy + danvatirsen A3 Durvalumab Durvalumab + oleclumab B2 Durvalumab Durvalumab + Investigator's choice of chemotherapy + danvatirsen B1 Nab-paclitaxel Durvalumab + Investigator's choice of chemotherapy B2 Carboplatin Durvalumab + Investigator's choice of chemotherapy + danvatirsen A1 Durvalumab Durvalumab B3 Nab-paclitaxel Durvalumab + investigator's choice of chemotherapy + oleclumab B5 AZD2936 AZD2936 + chemotherapy B3 Gemcitabine Durvalumab + investigator's choice of chemotherapy + oleclumab B5 Pemetrexed AZD2936 + chemotherapy B5 Carboplatin AZD2936 + chemotherapy B5 Cisplatin AZD2936 + chemotherapy B4 MEDI5752 MEDI5752 A4 MEDI5752 MEDI5752 A5 AZD2936 AZD2936 A2 Durvalumab Durvalumab + danvatirsen B1 Carboplatin Durvalumab + Investigator's choice of chemotherapy B1 Gemcitabine Durvalumab + Investigator's choice of chemotherapy B1 Pemetrexed Durvalumab + Investigator's choice of chemotherapy B1 Durvalumab Durvalumab + Investigator's choice of chemotherapy B1 Cisplatin Durvalumab + Investigator's choice of chemotherapy B2 Pemetrexed Durvalumab + Investigator's choice of chemotherapy + danvatirsen B3 Durvalumab Durvalumab + investigator's choice of chemotherapy + oleclumab B2 Gemcitabine Durvalumab + Investigator's choice of chemotherapy + danvatirsen B2 Cisplatin Durvalumab + Investigator's choice of chemotherapy + danvatirsen B3 Carboplatin Durvalumab + investigator's choice of chemotherapy + oleclumab B3 Pemetrexed Durvalumab + investigator's choice of chemotherapy + oleclumab B3 Cisplatin Durvalumab + investigator's choice of chemotherapy + oleclumab A3 Oleclumab Durvalumab + oleclumab B3 Oleclumab Durvalumab + investigator's choice of chemotherapy + oleclumab A2 Danvatirsen Durvalumab + danvatirsen B2 Danvatirsen Durvalumab + Investigator's choice of chemotherapy + danvatirsen
- Primary Outcome Measures
Name Time Method Assessment of AEs by CTCAE v5.0 From informed consent until the safety follow-up visit 3 months after the last dose of study drug, or until the final data cut-off (DCO) date, whichever is earlier. Assessment of safety and tolerability of each treatment arm
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Tumor assessments every 6-9 weeks until week 48-54, then every 12 or 18 weeks, depending on treatment arm until the earliest of radiological progression, death, withdrawal of consent, or final DCO (approximately 4 months after last patient randomized). Assessment of the efficacy of each treatment arm according to RECIST 1.1. ORR: The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR or PR
Duration of Response (DoR) Tumor assessments every 6-9 weeks until week 48-54, then every 12 or 18 weeks, depending on treatment arm until the earliest of radiological progression, death, withdrawal of consent, or final DCO (approximately 4 months after last patient randomized). Assessment of the efficacy of each treatment arm according to RECIST 1.1. DoR: Time from date of first detection of objective response until the date of objective radiological disease progression
Blood concentration of durvalumab and novel oncology therapies From Cycle 1 Day 1 until Cycle 6/7 Day 1 (21-28-day cycles) depending on arm, then every 3 cycles (except for Arms A5 & B5), at end of treatment (Arms A4 & B4, A5 & B5 only), and until 3 months following treatment discontinuation, or the final DCO date. Drug concentration of durvalumab and novel oncology therapies
Progression Free Survival (PFS) Tumor assessments every 6-9 weeks until week 48-54, then every 12/18 weeks based on arm until progression, death, withdrawal or final DCO. Further PFS data will be collected until 6 months after last patient dosed or final DCO Assessment of the efficacy of each treatment arm according to RECIST 1.1. PFS: Time from date of treatment assignment until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression)
Overall Survival (OS) OS data will be collected until death, 6 months after last patient dosed, or the final DCO date, whichever is earlier. OS: Time from date of treatment assignment until the date of death by any cause
Frequency of anti-drug antibodies (ADAs) for durvalumab and applicable novel oncology therapies From Cycle 1 Day 1 until Cycle 6/7 Day 1 (21-28-day cycles) depending on arm, then every 3 or 6 cycles (except for arms A5&B5), at end of treatment (arms A4&B4, A5&B5 only), until 3/6 months after treatment discontinuation, or the final DCO date. Investigation of the immunogenicity of durvalumab and each applicable novel oncology therapy in all applicable treatment arms
Trial Locations
- Locations (1)
Research Site
🇹🇭Hat Yai, Thailand