A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC

Study Overview
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Brief Summary
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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
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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).

Official Title
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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) (MAGELLAN)

Conditions
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Metastatic Non-Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Danvatirsen
* Drug: Oleclumab
* Drug: MEDI5752
* Drug: Pemetrexed
* Drug: Carboplatin
* Drug: Gemcitabine
* Drug: Cisplatin
* Drug: Nab-paclitaxel
* Drug: AZD2936


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1<br>Durvalumab | Drug: Durvalumab<br>* 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<br>* Other names: MEDI4736;|
| Experimental: A2<br>Durvalumab + danvatirsen | Drug: Durvalumab<br>* 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<br>* Other names: MEDI4736;Drug: Danvatirsen<br>* 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<br>* Other names: AZD9150;|
| Experimental: A3<br>Durvalumab + oleclumab | Drug: Durvalumab<br>* 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<br>* Other names: MEDI4736;Drug: Oleclumab<br>* 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<br>* Other names: MEDI9447;|
| Experimental: A4<br>MEDI5752 | Drug: MEDI5752<br>* MEDI5752 IV Every 3 weeks (q3w)<br>|
| Experimental: B1<br>Durvalumab + Investigator's choice of chemotherapy | Drug: Durvalumab<br>* 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<br>* Other names: MEDI4736;Drug: Pemetrexed<br>* 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<br>Drug: Carboplatin<br>* Carboplatin IV Day 1 of each 21-day cycle<br>Drug: Gemcitabine<br>* Gemcitabine IV Days 1 and 8 of each 21-day cycle<br>Drug: Cisplatin<br>* Cisplatin IV Day 1 of each 21-day cycle<br>Drug: Nab-paclitaxel<br>* Nab-paclitaxel IV Days 1, 8, and 15 of each 21-day cycle<br>|
| Experimental: B2<br>Durvalumab + Investigator's choice of chemotherapy + danvatirsen | Drug: Durvalumab<br>* 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<br>* Other names: MEDI4736;Drug: Danvatirsen<br>* 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<br>* Other names: AZD9150;Drug: Pemetrexed<br>* 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<br>Drug: Carboplatin<br>* Carboplatin IV Day 1 of each 21-day cycle<br>Drug: Gemcitabine<br>* Gemcitabine IV Days 1 and 8 of each 21-day cycle<br>Drug: Cisplatin<br>* Cisplatin IV Day 1 of each 21-day cycle<br>Drug: Nab-paclitaxel<br>* Nab-paclitaxel IV Days 1, 8, and 15 of each 21-day cycle<br>|
| Experimental: B3<br>Durvalumab + investigator's choice of chemotherapy + oleclumab | Drug: Durvalumab<br>* 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<br>* Other names: MEDI4736;Drug: Oleclumab<br>* 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<br>* Other names: MEDI9447;Drug: Pemetrexed<br>* 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<br>Drug: Carboplatin<br>* Carboplatin IV Day 1 of each 21-day cycle<br>Drug: Gemcitabine<br>* Gemcitabine IV Days 1 and 8 of each 21-day cycle<br>Drug: Cisplatin<br>* Cisplatin IV Day 1 of each 21-day cycle<br>Drug: Nab-paclitaxel<br>* Nab-paclitaxel IV Days 1, 8, and 15 of each 21-day cycle<br>|
| Experimental: B4<br>MEDI5752 | Drug: MEDI5752<br>* MEDI5752 IV Every 3 weeks (q3w)<br>|
| Experimental: A5<br>AZD2936 | Drug: AZD2936<br>* AZD2936 IV<br>|
| Experimental: B5<br>AZD2936 + chemotherapy | Drug: Pemetrexed<br>* 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<br>Drug: Carboplatin<br>* Carboplatin IV Day 1 of each 21-day cycle<br>Drug: Cisplatin<br>* Cisplatin IV Day 1 of each 21-day cycle<br>Drug: AZD2936<br>* AZD2936 IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of AEs by CTCAE v5.0 | Assessment of safety and tolerability of each treatment arm | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 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) | 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) | OS: Time from date of treatment assignment until the date of death by any cause | 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 | 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 | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, 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, Non-Small Cell Lung Carcinoma