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

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)

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: MEDI5752; Drug: Carboplatin; Drug: Gemcitabine; Drug: Cisplatin; Drug: Nab-paclitaxel; Drug: AZD2936; Drug: Durvalumab; Drug: Danvatirsen; Drug: Oleclumab; Drug: Pemetrexed

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).

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Research Site
  • Vienna, Austria, 1140
    • Research Site
• Belgium
  • Edegem, Belgium, 2650
    • Research Site
• Poland
  • Bialystok, Poland, 15-027
    • Research Site
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Gdansk, Poland, 80-214
    • Research Site
  • Grudziądz, Poland, 86-300
    • Research Site
  • Lodz, Poland, 90-302
    • Research Site
  • Olsztyn, Poland, 10-357
    • Research Site
  • Tomaszów Mazowiecki, Poland, 97-200
    • Research Site
  • Warsaw, Poland, 02-781
    • Research Site
  • Wroclaw, Poland, 53-413
    • Research Site
• Russia
  • Krasnoyarsk, Russia, 660133
    • Research Site
  • Moscow, Russia, 115478
    • Research Site
  • Saint Petersburg, Russia, 197758
    • Research Site
  • Saint Petersburg, Russia, 191014
    • Research Site
• South Korea
  • Cheongju-si, South Korea, 28644
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
  • Seoul, South Korea, 110-744
    • Research Site
• Spain
  • Barcelona, Spain, 08025
    • Research Site
  • Barcelona, Spain, 8003
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Seville, Spain, 41013
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 402
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
  • Taoyuan, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Sandip Patel, MD, UCSD Morres Cancer Center; Principal Investigator: Chih-Hsin Yang, MD, National Taiwan University Hospital

Publications and helpful links

General Publications

• Cho BC, Charoentum C, Kim DW, Yang CT, Dziadziuszko R, Geater SL, Mann H, Afshar-Imani B, Lyfar P, Yang JC, Patel SP. MAGELLAN arms B1 and B3: Durvalumab plus chemotherapy with and without oleclumab in treatment-naive metastatic non-small-cell lung cancer. Lung Cancer. 2026 Jan;211:108834. doi: 10.1016/j.lungcan.2025.108834. Epub 2025 Nov 7.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2018
• Primary Completion (Actual): May 23, 2023
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; Non-Small Cell Lung Carcinoma; Non-Small Cell; Metastatic Non-Small Cell Lung Cancer; First-Line Stage IV Metastatic Non-Small Cell Lung Cancer; Stage IV Metastatic Non-Small Cell Lung Cancer; Non-Small Cell Lung
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Pemetrexed; Gemcitabine; Carboplatin; Cisplatin; durvalumab; 130-nm albumin-bound paclitaxel; danvatirsen
• Other Study ID Numbers: D933IC00001; 2018-001748-74 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No