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)

• Register: ClinicalTrials.gov
• Last refreshed on: 29 April 2024
• Main ID: NCT02453282
• Date of registration: 20/05/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: 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) MYSTIC
• Scientific 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).
• Date of first enrolment: July 21, 2015
• Target sample size: 1118
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02453282
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Russian Federation, Spain, Switzerland, Taiwan, Thailand, United States, Vietnam

Contacts

• Name: Stuart McIntosh, MD
• Affiliation: AstraZeneca, Alderley Park, Cheshire, UK

• Name: Naiyer Rizvi, MD
• Affiliation: Columbia University Medical Center, New York, NY, USA

Key inclusion & exclusion 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]



Age minimum: 18 Years
Age maximum: 130 Years
Gender: All

Health Condition(s) or Problem(s) studied

Non-Small-Cell Lung Carcinoma NSCLC

Intervention(s)

Biological: MEDI4736 (Durvalumab)+Tremelimumab

Drug: Paclitaxel + Carboplatin

Drug: Gemcitabine + Cisplatin

Drug: Pemetrexed + Carboplatin

Biological: Tremelimumab

Drug: Pemetrexed + Cisplatin

Biological: MEDI4736 (Durvalumab)

Drug: Gemcitabine + Carboplatin

Primary Outcome(s)

Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy [Time Frame: 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).]

Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy [Time Frame: 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).]

Secondary Outcome(s)

DoR; FAS Population [Time Frame: 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).]

ORR; FAS Population [Time Frame: 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).]

Percentage of Participants APF12; FAS Population [Time Frame: Tumour scans performed at baseline then every 6 weeks up to 12 months.]

Ctrough_ss of Tremelimumab [Time Frame: Pre-dose at Week 12.]

Number of Participants With ADA Response to Tremelimumab [Time Frame: At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.]

Serum Concentrations of Tremelimumab [Time Frame: Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3.]

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 [Time Frame: 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.]

Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population [Time Frame: Tumour scans performed at baseline then every 6 weeks up to 12 months.]

Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab [Time Frame: Within 1 hour after end of infusion on infusion day at Week 12.]

Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population [Time Frame: 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).]

Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population [Time Frame: 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).]

ORR; PD-L1 (TC >=1%) Analysis Set Population [Time Frame: 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).]

DoR; PD-L1 (TC >=1%) Analysis Set Population [Time Frame: 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).]

Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population [Time Frame: 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).]

Cmax_ss of Tremelimumab [Time Frame: Within 1 hour after end of infusion on infusion day at Week 12.]

OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy [Time Frame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).]

Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab [Time Frame: At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.]

OS; FAS Population [Time Frame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).]

Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population [Time Frame: Tumour scans performed at baseline then every 6 weeks up to 12 months.]

OS; PD-L1 (TC >=1%) Analysis Set Population [Time Frame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).]

PFS; PD-L1 (TC >=1%) Analysis Set Population [Time Frame: 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).]

PFS; FAS Population [Time Frame: 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).]

Serum Concentrations of Durvalumab [Time Frame: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, and at follow-up Month 3.]

PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy [Time Frame: 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).]

PFS2; PD-L1 (TC >=1%) Analysis Set Population [Time Frame: 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).]

PFS2; FAS Population [Time Frame: 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).]

Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab [Time Frame: Pre-dose at Week 12.]

Secondary ID(s)

D419AC00001

2015-001279-39

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/11/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02453282