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)
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
175
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
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
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
Assessment of AEs by CTCAE v5.0
Assessment of safety and tolerability of each treatment arm
Time frame: 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.
Objective Response Rate (ORR)
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
Time frame: 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).
Duration of Response (DoR)
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
Time frame: 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).
Progression Free Survival (PFS)
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)
Time frame: 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
Overall Survival (OS)
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MEDI5752 IV Every 3 weeks (q3w)
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
Carboplatin IV Day 1 of each 21-day cycle
Gemcitabine IV Days 1 and 8 of each 21-day cycle
Cisplatin IV Day 1 of each 21-day cycle
Nab-paclitaxel IV Days 1, 8, and 15 of each 21-day cycle
AZD2936 IV
Research Site
Iowa City, Iowa, United States
Research Site
Pittsburgh, Pennsylvania, United States
Research Site
Nashville, Tennessee, United States
Research Site
Salzburg, Austria
Research Site
Vienna, Austria
Research Site
Edegem, Belgium
Research Site
Bialystok, Poland
Research Site
Bydgoszcz, Poland
Research Site
Gdansk, Poland
Research Site
Grudziądz, Poland
...and 31 more locations
OS: Time from date of treatment assignment until the date of death by any cause
Time frame: OS data will be collected until death, 6 months after last patient dosed, or the final DCO date, whichever is earlier.
Blood concentration of durvalumab and novel oncology therapies
Drug concentration of durvalumab and novel oncology therapies
Time frame: 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.
Frequency of anti-drug antibodies (ADAs) for durvalumab and applicable novel oncology therapies
Investigation of the immunogenicity of durvalumab and each applicable novel oncology therapy in all applicable treatment arms
Time frame: 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.