A Phase 3 interventional study of MEDI4736 and PLACEBO in Non-Small Cell Lung Cancer, sponsored by AstraZeneca. Completed at 236 sites in 26 countries. Open to participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2023-10-10.
Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment
A Global Study to Assess the Effects of MEDI4736 following concurrent chemoradiation in Patients with Stage III Unresectable Non-Small Cell Lung Cancer.
A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre, International Study of MEDI4736 as Sequential Therapy in Patients with Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Concurrent Chemoradiation Therapy (PACIFIC)
6,645 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,665 are open to participants now.
This study's enrollment of 713 is above the median of 62 across 5,327 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →AstraZeneca is the lead sponsor of 3,492 studies on the registry; 265 are open to participants now.
Of its 368 completed or terminated interventional studies of FDA-regulated products, 176 (48%) have results posted.
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Exclusion Criteria:
MEDI4736 (intravenous infusion)
Drug: MEDI4736
Placebo (matching placebo for intravenous infusion)
Other: PLACEBO
MEDI4736 by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier . The 2:1 ratio (MEDI4736 to placebo).
PLACEBO by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier . The 2:1 ratio (MEDI4736 to placebo).
Progression Free Survival Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
PFS was defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). Progression was defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PFS was calculated using the Kaplan-Meier technique.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Overall Survival
OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using the Kaplan-Meier technique.
Time frame: From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Objective Response Rate (ORR) Based on BICR Assesments According to RECIST 1.1
ORR was defined as the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 for target lesions: CR: Disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Duration of Response (DoR) Based on BICR Assessments According to RECIST 1.1
DoR was defined as the time from date for first documented response of CR or PR until the first documented response of progression per RECIST 1.1 or death in the absence of progression. DoR was calculated using the Kaplan-Meier technique.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Proportion of Patients Alive and Progression Free at 12 Months From (APF12) Based on BICR Assessments According to RECIST 1.1
APF12 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Proportion of Patients Alive and Progression Free at 18 Months From (APF18) Based on BICR Assessments According to RECIST 1.1
APF18 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 18 months after randomization per the Kaplan-Meier estimate of PFS at 18 months.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Time to Death or Distant Metastasis (TTDM) Based on BICR Assessments According to RECIST 1.1
TTDM was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that was outside of the radiation field according to RECIST 1.1 or proven by biopsy. TTDM was calculated using the Kaplan-Meier technique.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Percentage of Patients Alive at 24 Months (OS24)
OS24 was defined as the percentage of patients who were alive at 24 months after randomization per the Kaplan-Meier estimate of OS at 24 months.
Time frame: From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Time to Second Progression or Death (PFS2)
PFS2 was defined as the time from randomization to the time of the second progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could have involved any of the following: objective radiological, symptomatic progression, or death. RECIST assessments were not collected for assessment of PFS2. PFS2 was calculated using the Kaplan-Meier technique.
Time frame: Following confirmed progression, patients were assessed every ~12 weeks until second disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL), Assessed Using European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30)
Global health status/HRQoL was assessed using the EORTC QLQ-C30 global QoL scale which includes 2 items from the QLQ-C30: "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall QoL during the past week?" (Item 30). Scores from 0 to 100 were derived for each item with higher scores indicating a better health status. Time to deterioration for global health status/HRQoL was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in global health status/HRQoL from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful deterioration. Time to deterioration was calculated using the Kaplan-Meier technique.
Time frame: At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Time to Deterioration of Primary Patient-Reported Outcome (PRO) Symptoms, Assessed Using European Organization for Research and Treatment of Cancer QoL Lung Cancer Module (EORTC QLQ-LC13)
The EORTC QLQ-LC13 is a lung cancer specific module from the EORTC comprising 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, chest pain, arm/shoulder pain, and other pain), treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. Scores from 0 to 100 were derived for each symptom item with higher scores representing greater symptom severity. Time to symptom deterioration was defined as time from randomization until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration. Results are presented for time to deterioration in the following PRO endpoints identified as primary for EORTC QLQ-LC13: dyspnea, cough, hemoptysis and chest pain. Time to deterioration was calculated using the Kaplan-Meier technique.
Time frame: At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations
To evaluate PK, blood samples were collected pre-dose and post-dose and trough and peak serum concentrations of durvalumab, respectively, were determined. Pre-dose samples were taken within 60 minutes before infusion and post-dose samples were taken within 10 minutes after the end of infusion.
Time frame: Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48, and post-dose on Day 1 (Week 0) and Week 24. Analysis performed at 22 Mar 2018 DCO.
Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab
ADA positive post-baseline only was also referred to as treatment-induced ADA positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted by ≥4-fold following drug administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Confirmed ADA positive samples were subsequently tested in a neutralizing antibody assay.
Time frame: Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48. Analysis performed at 22 Mar 2018 DCO.
Patients were randomized between 09 May 2014 and 22 Apr 2016 in 235 study centers across 26 countries. Data cut-off (DCO) date for analysis of progression-free survival (PFS) and PFS rates at 12 and 18 months: 13 Feb 2017; DCO date for analysis of overall survival (OS) and all other secondary outcome measures: 22 Mar 2018; DCO date for completion of long-term survival: 11 Jan 2021.
| Milestone | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Started | 476 | 237 |
| Full analysis set (fas) | 476 | 237 |
| Received treatment | 473 | 236 |
| Safety analysis set | 475 | 234 |
| Completed 12 months of treatment | 232 | 82 |
| Completed | 178 | 68 |
| Not completed | 298 | 169 |
| Withdrew: Withdrawal by subject | 30 | 16 |
| Withdrew: Lost to follow-up | 8 | 3 |
| Withdrew: Death | 260 | 149 |
| Withdrew: Missing termination reason | 0 | 1 |
PFS was defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). Progression was defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PFS was calculated using the Kaplan-Meier technique.
| Months | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Progression Free Survival Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | 16.8 (13.0 to 18.1) | 5.6 (4.6 to 7.8) |
OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using the Kaplan-Meier technique.
| Months | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Overall Survival | NA (34.7 to NA) | 28.7 (22.9 to NA) |
ORR was defined as the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 for target lesions: CR: Disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.
| Percentage of patients | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Objective Response Rate (ORR) Based on BICR Assesments According to RECIST 1.1 | 30.0 (25.79 to 34.53) | 17.8 (12.95 to 23.65) |
DoR was defined as the time from date for first documented response of CR or PR until the first documented response of progression per RECIST 1.1 or death in the absence of progression. DoR was calculated using the Kaplan-Meier technique.
| Months | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Duration of Response (DoR) Based on BICR Assessments According to RECIST 1.1 | NA (27.4 to NA) | 18.4 (6.7 to 24.5) |
APF12 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months.
| Percentage of patients | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Proportion of Patients Alive and Progression Free at 12 Months From (APF12) Based on BICR Assessments According to RECIST 1.1 | 55.9 (51.0 to 60.4) | 35.3 (29.0 to 41.7) |
APF18 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 18 months after randomization per the Kaplan-Meier estimate of PFS at 18 months.
| Percentage of patients | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Proportion of Patients Alive and Progression Free at 18 Months From (APF18) Based on BICR Assessments According to RECIST 1.1 | 44.2 (37.7 to 50.5) | 27.0 (19.9 to 34.5) |
TTDM was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that was outside of the radiation field according to RECIST 1.1 or proven by biopsy. TTDM was calculated using the Kaplan-Meier technique.
| Months | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Time to Death or Distant Metastasis (TTDM) Based on BICR Assessments According to RECIST 1.1 | 28.3 (24.0 to 34.9) | 16.2 (12.5 to 21.1) |
OS24 was defined as the percentage of patients who were alive at 24 months after randomization per the Kaplan-Meier estimate of OS at 24 months.
| Percentage of patients | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Percentage of Patients Alive at 24 Months (OS24) | 66.3 (61.7 to 70.4) | 55.6 (48.9 to 61.8) |
PFS2 was defined as the time from randomization to the time of the second progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could have involved any of the following: objective radiological, symptomatic progression, or death. RECIST assessments were not collected for assessment of PFS2. PFS2 was calculated using the Kaplan-Meier technique.
| Months | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Time to Second Progression or Death (PFS2) | 28.3 (25.1 to 34.7) | 17.1 (14.5 to 20.7) |
Global health status/HRQoL was assessed using the EORTC QLQ-C30 global QoL scale which includes 2 items from the QLQ-C30: "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall QoL during the past week?" (Item 30). Scores from 0 to 100 were derived for each item with higher scores indicating a better health status. Time to deterioration for global health status/HRQoL was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in global health status/HRQoL from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful deterioration. Time to deterioration was calculated using the Kaplan-Meier technique.
| Months | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL), Assessed Using European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30) | 7.4 (5.5 to 9.3) | 5.7 (4.2 to 10.5) |
The EORTC QLQ-LC13 is a lung cancer specific module from the EORTC comprising 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, chest pain, arm/shoulder pain, and other pain), treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. Scores from 0 to 100 were derived for each symptom item with higher scores representing greater symptom severity. Time to symptom deterioration was defined as time from randomization until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration. Results are presented for time to deterioration in the following PRO endpoints identified as primary for EORTC QLQ-LC13: dyspnea, cough, hemoptysis and chest pain. Time to deterioration was calculated using the Kaplan-Meier technique.
| Months | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| Dyspnea | 2.8 (1.9 to 3.7) | 3.7 (2.3 to 4.1) |
| Cough | 5.6 (4.5 to 7.3) | 5.6 (3.7 to 6.0) |
| Hemoptysis | NA (NA to NA) | 29.6 (21.2 to NA) |
| Chest pain | 11.1 (7.4 to 18.6) | 8.3 (5.6 to 13.8) |
To evaluate PK, blood samples were collected pre-dose and post-dose and trough and peak serum concentrations of durvalumab, respectively, were determined. Pre-dose samples were taken within 60 minutes before infusion and post-dose samples were taken within 10 minutes after the end of infusion.
| Micrograms per milliliter | Durvalumab (MEDI4736) |
|---|---|
| Week 0: peak concentration | 191.00 ± 72.4 |
| Week 8: trough concentration | 120.00 ± 62.2 |
| Week 24: trough concentration | 177.00 ± 47.9 |
| Week 24: peak concentration | 373.00 ± 43.6 |
| Week 48: trough concentration | 186.00 ± 67.4 |
ADA positive post-baseline only was also referred to as treatment-induced ADA positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted by ≥4-fold following drug administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Confirmed ADA positive samples were subsequently tested in a neutralizing antibody assay.
| Participants | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| ADA positive at any visit | 19 | 10 |
| ADA positive post-baseline only | 8 | 5 |
| Treatment-boosted ADA positive | 0 | 0 |
| ADA positive at baseline and post-baseline | 2 | 2 |
| ADA positive at baseline only | 9 | 3 |
| ADA persistently positive | 5 | 5 |
| ADA transient positive | 5 | 2 |
| Neutralizing antibodies positive at any visit | 3 | 0 |
Collected over Serious and Other (non-serious) treatment-emergent adverse event (TEAE) data collected during the 12-month treatment period. All-cause mortality (death due to any cause) collected for entire duration of the study. Assessed until 11 Jan 2021 DCO for completion of long-term survival; approximately 5 years from last patient enrolled.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Durvalumab (MEDI4736) | 262/475 (55.2%) | 138/475 (29.1%) | 436/475 (91.8%) |
| Placebo | 154/234 (65.8%) | 54/234 (23.1%) | 212/234 (90.6%) |
| Event | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| PneumoniaInfections and infestations | 33/475 | 14/234 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 17/475 | 7/234 |
| Radiation pneumonitisInjury, poisoning and procedural complications | 17/475 | 4/234 |
| Atrial fibrillationCardiac disorders | 5/475 | 0/234 |
| Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 5/475 | 0/234 |
| DiarrhoeaGastrointestinal disorders | 1/475 | 2/234 |
| SepsisInfections and infestations | 4/475 | 2/234 |
| FatigueGeneral disorders | 0/475 | 2/234 |
| Pneumonia necrotisingInfections and infestations | 0/475 | 2/234 |
| Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders | 0/475 | 2/234 |
| Event | Durvalumab (MEDI4736) | Placebo |
|---|---|---|
| CoughRespiratory, thoracic and mediastinal disorders | 169/475 | 59/234 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 106/475 | 57/234 |
| FatigueGeneral disorders | 114/475 | 47/234 |
| DiarrhoeaGastrointestinal disorders | 87/475 | 46/234 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 83/475 | 44/234 |
| Radiation pneumonitisInjury, poisoning and procedural complications | 80/475 | 33/234 |
| PyrexiaGeneral disorders | 70/475 | 22/234 |
| Decreased appetiteMetabolism and nutrition disorders | 69/475 | 29/234 |
| NauseaGastrointestinal disorders | 68/475 | 31/234 |
| AstheniaGeneral disorders | 51/475 | 31/234 |
Baseline analysis was based on the FAS consisting of all randomized patients.
| Age, Continuous(years) | Durvalumab (MEDI4736) | Placebo | Total |
|---|---|---|---|
| Mean | 63.0 ± 8.66 | 62.6 ± 9.64 | 62.9 ± 8.99 |
| Sex: Female, Male(Participants) | Durvalumab (MEDI4736) | Placebo | Total |
|---|---|---|---|
| Female | 142 | 71 | 213 |
| Male | 334 | 166 | 500 |
| Race/Ethnicity, Customized(Participants) | Durvalumab (MEDI4736) | Placebo | Total |
|---|---|---|---|
| White | 337 | 157 | 494 |
| Black or African American | 12 | 2 | 14 |
| Asian | 120 | 72 | 192 |
| Native Hawaiian or Pacific Islander | 1 | 1 | 2 |
| American Indian or Alaska Native | 4 | 5 | 9 |
| Other | 1 | 0 | 1 |
| Missing | 1 | 0 | 1 |
| Smoking History(Participants) | Durvalumab (MEDI4736) | Placebo | Total |
|---|---|---|---|
| Non-smoker | 43 | 21 | 64 |
| Ex-smoker | 354 | 178 | 532 |
| Current smoker | 79 | 38 | 117 |
Showing the first 100 of 236 sites across 26 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting information: Study protocol, Statistical analysis plan
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.
Access criteria: When a request has been approved AstraZeneca will provide access to the deidentified 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.
Data sharing details ↗ · astrazenecagroup-dt.pharmacm.com
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Studies of the drug tested here: Durvalumab
Carcinoma, Non-Small-Cell Lung →