Clinical trial NCT02453282: Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC)
Official title: A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy or MEDI4736 Monotherapy Versus Standard of Care Platinum-Based Chemotherapy in First Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC)(MYSTIC).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-Small-Cell Lung Carcinoma NSCLC
Keywords: NSCLC, PD-L1, MEDI4736, Tremelimumab, PFS, OS
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-05-25
Enrollment: 1118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus platinum-based SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type locally advanced or metastatic NSCLC

Detailed description: Patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or Standard of Care (SoC) therapy.

Eligibility criteria: Inclusion Criteria:

For inclusion in the study, patients should fulfill the following criteria:

* Aged at least 18 years
* Documented evidence of Stage IV NSCLC
* No sensitizing EGFR mutation or ALK rearrangement
* No prior chemotherapy or any other systemic therapy for recurrent/metastatic NSCLC
* World Health Organization (WHO) Performance Status of 0 or 1

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

1. Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant
2. Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
3. Prior exposure to Immunomodulatory therapy (IMT), including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies, excluding therapeutic anticancer vaccines
4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\]

Primary outcomes:
measure: Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy
timeFrame: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcomes:
measure: OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
timeFrame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: OS; PD-L1 (TC >=1%) Analysis Set Population
timeFrame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: OS; FAS Population
timeFrame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: PFS; PD-L1 (TC >=1%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: PFS; FAS Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: ORR; PD-L1 (TC >=1%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: ORR; FAS Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: DoR; PD-L1 (TC >=1%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: DoR; FAS Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
measure: Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
measure: Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
measure: Percentage of Participants APF12; FAS Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
measure: Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
measure: PFS2; PD-L1 (TC >=1%) Analysis Set Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
measure: PFS2; FAS Population
timeFrame: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
measure: Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months
timeFrame: At baseline then every 4 weeks for the first 8 weeks relative to the date of randomization, then every 8 weeks until second progression/death, whichever comes first. Assessed up to 12 months.
measure: Serum Concentrations of Durvalumab
timeFrame: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, and at follow-up Month 3.
measure: Serum Concentrations of Tremelimumab
timeFrame: Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3.
measure: Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab
timeFrame: Within 1 hour after end of infusion on infusion day at Week 12.
measure: Cmax_ss of Tremelimumab
timeFrame: Within 1 hour after end of infusion on infusion day at Week 12.
measure: Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab
timeFrame: Pre-dose at Week 12.
measure: Ctrough_ss of Tremelimumab
timeFrame: Pre-dose at Week 12.
measure: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
timeFrame: At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.
measure: Number of Participants With ADA Response to Tremelimumab
timeFrame: At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.
Other outcomes:
Locations:
city: Scottsdale
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state: Arizona
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state: Arizona
city: Yuma
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state: New Jersey
city: Mineola
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city: New York
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state: New York
city: New York
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state: New York
city: New York
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city: Port Macquarie
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city: Brussels
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city: Charleroi
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city: Leuven
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city: Liège
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city: Kingston
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state: Ontario
city: Newmarket
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state: Ontario
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city: Sudbury
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city: Brest Cedex
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city: Lille
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city: Lyon Cedex 08
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city: Aachen
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city: Bad Berka
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city: Berlin
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city: Münster
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city: Oldenburg
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city: San Giovanni Rotondo
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city: Fukushima-shi
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country: Japan
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city: Busan
country: Korea, Republic of
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city: Changwon-si
country: Korea, Republic of
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city: Cheongju-si
country: Korea, Republic of
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city: Daegu
country: Korea, Republic of
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city: Daegu
country: Korea, Republic of
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city: Daejeon
country: Korea, Republic of
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city: Goyang-si
country: Korea, Republic of
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city: Incheon
country: Korea, Republic of
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city: Jinju-si
country: Korea, Republic of
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city: Seongnam-si
country: Korea, Republic of
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city: Seongnam-Si
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Suwon-si
country: Korea, Republic of
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city: Ulsan
country: Korea, Republic of
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city: Amsterdam
country: Netherlands
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city: Arnhem
country: Netherlands
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city: Breda
country: Netherlands
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city: Den Bosch
country: Netherlands
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city: Groningen
country: Netherlands
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city: Maastricht
country: Netherlands
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city: Rotterdam
country: Netherlands
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Alicante
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
facility: Research Site
city: Gerona
country: Spain
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city: Jaén
country: Spain
facility: Research Site
city: León
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
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city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Bellinzona
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Tao-Yuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Hanoi City
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: AstraZeneca, Alderley Park, Cheshire, UK
name: Stuart McIntosh, MD
role: STUDY_DIRECTOR
affiliation: Columbia University Medical Center, New York, NY, USA
name: Naiyer Rizvi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garon EB, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, Robinet G, Le Moulec S, Natale R, Schneider J, Shepherd FA, Garassino MC, Geater SL, Szekely ZP, Van Ngoc T, Liu F, Scheuring U, Patel N, Peters S, Rizvi NA. Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). Clin Lung Cancer. 2021 Jul;22(4):301-312.e8. doi: 10.1016/j.cllc.2021.02.010. Epub 2021 Feb 19.
citation: Rizvi NA, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, van den Heuvel MM, Cobo M, Vicente D, Smolin A, Moiseyenko V, Antonia SJ, Le Moulec S, Robinet G, Natale R, Schneider J, Shepherd FA, Geater SL, Garon EB, Kim ES, Goldberg SB, Nakagawa K, Raja R, Higgs BW, Boothman AM, Zhao L, Scheuring U, Stockman PK, Chand VK, Peters S; MYSTIC Investigators. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):661-674. doi: 10.1001/jamaoncol.2020.0237.