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

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03819465

Collaborator

(none)

258

Enrollment

Locations

Arms

86.9

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Metastatic Non-Small Cell Lung Cancer (NSCLC)	Drug: Durvalumab Drug: Danvatirsen Drug: Oleclumab Drug: MEDI5752 Drug: Pemetrexed Drug: Carboplatin Drug: Gemcitabine Drug: Cisplatin Drug: Nab-paclitaxel Drug: AZD2936	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

258 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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).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)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Dec 27, 2018

Anticipated Primary Completion Date :

Mar 26, 2026

Anticipated Study Completion Date :

Mar 26, 2026

Arms and Interventions

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 C5D1 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 C5D1 Other Names: MEDI4736 Drug: Danvatirsen Danvatirsen IV Loading dose C1D1, C1D3, and C1D5 then once a week (q1w) starting at C1D8 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 C5D1 Other Names: MEDI4736 Drug: Oleclumab Oleclumab IV Cohort A: Every 2 weeks (q2w) for first 2 cycles, then every 4 weeks (q4w) starting at C3D1 Cohort B: Every 3 weeks (q3w) for the first 4 cycles, then every 4 weeks (q4w) starting at C5D1 Other Names: MEDI9447
Experimental: A4 MEDI5752	Drug: MEDI5752 MEDI5752 IV Every 3 weeks (q3w)
Experimental: B1 Durvalumab + Investigator's choice of chemotherapy	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 C5D1 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 q3w or 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 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
Experimental: B2 Durvalumab + Investigator's choice of chemotherapy + 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 C5D1 Other Names: MEDI4736 Drug: Danvatirsen Danvatirsen IV Loading dose C1D1, C1D3, and C1D5 then once a week (q1w) starting at C1D8 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 q3w or 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 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
Experimental: B3 Durvalumab + investigator's choice of chemotherapy + 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 C5D1 Other Names: MEDI4736 Drug: Oleclumab Oleclumab IV Cohort A: Every 2 weeks (q2w) for first 2 cycles, then every 4 weeks (q4w) starting at C3D1 Cohort B: Every 3 weeks (q3w) for the first 4 cycles, then every 4 weeks (q4w) starting at C5D1 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 q3w or 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 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
Experimental: B4 MEDI5752	Drug: MEDI5752 MEDI5752 IV Every 3 weeks (q3w)
Experimental: A5 AZD2936	Drug: AZD2936 AZD2936 IV
Experimental: B5 AZD2936 + chemotherapy	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 q3w or 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 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

Outcome Measures

Primary Outcome Measures

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]
Assessment of safety and tolerability of each treatment arm

Secondary Outcome Measures

Objective Response Rate (ORR) [Approximately 24 months]
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 occur every 6-9 weeks until week 48-54 & then every 12 or 18 weeks, depending on treatment arm until confirmed radiological progression, death, withdrawal of consent or study completion, up to approximately 24 months]
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 occur every 6-9 weeks until week 48-54 & then every 12/18 weeks based on treatment arm until progression, death, withdrawal or study completion up to 24 months. Further PFS data will be collected until 6 months post-last patient dosed]
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) [Approximately 42 months. Additional OS data will be collected until approximately 6 months post-last patient dosed]
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 or 7 Day 1 (each cycle is 21 or 28 days) depending on treatment 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]
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 or 7 Day 1 (21- or 28-day cycles) depending on treatment arm, then every 3 or 6 cycles (except for arms A5&B5), at end of treatment (arms A4&B4, A5&B5 only), until 3 or 6 months following treatment discontinuation]
Investigation of the immunogenicity of durvalumab and each applicable novel oncology therapy in all applicable treatment arms

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Iowa City	Iowa	United States	52242
2	Research Site	Pittsburgh	Pennsylvania	United States	15212
3	Research Site	Nashville	Tennessee	United States	37203
4	Research Site	Salzburg		Austria	5020
5	Research Site	Wien		Austria	1140
6	Research Site	Edegem		Belgium	2650
7	Research Site	Edmonton	Alberta	Canada	T6G 1Z2
8	Research Site	Toronto		Canada	M5G 2M9
9	Research Site	Seoul		Korea, Republic of	03080
10	Research Site	Seoul		Korea, Republic of	03722
11	Research Site	Seoul		Korea, Republic of	05505
12	Research Site	Seoul		Korea, Republic of	06351
13	Research Site	Bialystok		Poland	15-027
14	Research Site	Bydgoszcz		Poland	85-796
15	Research Site	Gdańsk		Poland	80-214
16	Research Site	Grudziądz		Poland	86-300
17	Research Site	Olsztyn		Poland	10-357
18	Research Site	Tomaszów Mazowiecki		Poland	97-200
19	Research Site	Warszawa		Poland	02-781
20	Research Site	Wroclaw		Poland	53-413
21	Research Site	Krasnoyarsk		Russian Federation	660133
22	Research Site	Moscow		Russian Federation	115478
23	Research Site	Saint Petersburg		Russian Federation	197758
24	Research Site	Sankt-Peterburg		Russian Federation	197758
25	Research Site	St.Petersburg		Russian Federation	191014
26	Research Site	Barcelona		Spain	08025
27	Research Site	Barcelona		Spain	08035
28	Research Site	Barcelona		Spain	8003
29	Research Site	Madrid		Spain	28034
30	Research Site	Madrid		Spain	28041
31	Research Site	Sevilla		Spain	41013
32	Research Site	Kaohsiung		Taiwan	807
33	Research Site	Taichung City		Taiwan	402
34	Research Site	Taichung		Taiwan	40705
35	Research Site	Tainan City		Taiwan	70403
36	Research Site	Taipei		Taiwan	10002
37	Research Site	Taipei		Taiwan	112
38	Research Site	Taipei		Taiwan	235
39	Research Site	Taoyuan		Taiwan	333
40	Research Site	Bangkok		Thailand	10330
41	Research Site	Bangkok		Thailand	10700
42	Research Site	Chiang Mai		Thailand	50200
43	Research Site	Hat Yai		Thailand	90110