Metastatic Non-Small Cell Lung Cancer (NSCLC)
Conditions
Keywords
First-Line Stage IV Metastatic Non-Small Cell Lung Cancer, Stage IV Metastatic Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer, Non-Small Cell Lung, Non-Small Cell, NSCLC, Non-Small Cell Lung Carcinoma
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).
Interventions
DRUGDurvalumab
Durvalumab IV Cohort A: Every 4 weeks (q4w) Cohort B: Every 3 weeks (q3w) for the first 4 cycles, then every 4 weeks (q4w) starting at Cycle 5 Day 1
DRUGDanvatirsen
Danvatirsen IV Loading dose Cycle 1 Day 1, Cycle 1 Day 3, and Cycle 1 Day 5 then once a week (q1w) starting at Cycle 1 Day 8
DRUGOleclumab
Oleclumab IV Cohort A: Every 2 weeks (q2w) for first 2 cycles, then every 4 weeks (q4w) starting at Cycle 3 Day 1 Cohort B: Every 3 weeks (q3w) for the first 4 cycles, then every 4 weeks (q4w) starting at Cycle 5 Day 1
DRUGMEDI5752
MEDI5752 IV Every 3 weeks (q3w)
DRUGPemetrexed
Pemetrexed IV Day 1 of each 21-day cycle Arm B1: Day 1 of each 21-day cycle for the first 4 cycles then either every 3 weeks (q3w) or every 4 weeks (q4w) (per investigator discretion) thereafter Arm B2 and B3: Day 1 of each 21-day cycle for the first 4 cycles then Day 1 of each 28-day cycle (q4w) thereafter Arm B5: Day 1 of each 21-day cycle throughout the study
DRUGCarboplatin
Carboplatin IV Day 1 of each 21-day cycle
DRUGGemcitabine
Gemcitabine IV Days 1 and 8 of each 21-day cycle
DRUGCisplatin
Cisplatin IV Day 1 of each 21-day cycle
DRUGNab-paclitaxel
Nab-paclitaxel IV Days 1, 8, and 15 of each 21-day cycle
DRUGAZD2936
AZD2936 IV
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Treatment arms for MEDI5752 (Arms A4 and B4) will enroll 42 and 60 patients, respectively. Arm B5 (AZD2936+chemotherapy) will enroll 60 patients. For all other treatment arms, 30 patients will be enrolled into each arm; additional patients may be enrolled in order to have 30 evaluable patients per arm (ie, dosed).
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Austria, Belgium, Poland, Russia, South Korea, Spain, Taiwan, Thailand, United States
Contacts
PRINCIPAL_INVESTIGATORSandip Patel, MD
UCSD Morres Cancer Center
PRINCIPAL_INVESTIGATORChih-Hsin Yang, MD
National Taiwan University Hospital
Outcome results
None listed