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Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON). (POSEIDON)

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ClinicalTrials.gov Identifier: NCT03164616
Recruitment Status : Recruiting
First Posted : May 23, 2017
Results First Posted : April 7, 2022
Last Update Posted : June 7, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE May 22, 2017
First Posted Date  ICMJE May 23, 2017
Results First Submitted Date  ICMJE March 11, 2022
Results First Posted Date  ICMJE April 7, 2022
Last Update Posted Date June 7, 2022
Actual Study Start Date  ICMJE June 1, 2017
Actual Primary Completion Date March 12, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2022)
  • Progression-Free Survival (PFS); D + SoC Compared With SoC Alone [ Time Frame: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months). ]
    PFS (per RECIST version 1.1 [RECIST 1.1] using Blinded Independent Central Review [BICR] assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique. The final analysis of PFS in the global cohort was pre-specified after approximately 497 BICR PFS events occurred across the D + SoC and SoC alone treatment arms (75% maturity).
  • Overall Survival (OS); D + SoC Compared With SoC Alone [ Time Frame: From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months). ]
    OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The final analysis of OS in the global cohort was pre-specified after approximately 532 OS events occurred across the D + SoC and SoC alone treatment arms (80% maturity).
Original Primary Outcome Measures  ICMJE
 (submitted: May 22, 2017)
Progression-free survival (PFS) using Blinded Independent Central Review (BICR) assessments according to RECIST 1.1 [ Time Frame: Up to 3 years after first patient randomized ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2022)
  • PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC [ Time Frame: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months. ]
    PFS (per RECIST 1.1 using BICR assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique.
  • OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC [ Time Frame: From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months). ]
    OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
  • Objective Response Rate (ORR) [ Time Frame: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months). ]
    ORR (per RECIST 1.1 using BICR assessments) was defined as the percentage of patients with at least one visit response of complete response (CR) or partial response (PR). Results are presented for the pre-specified ORR analysis using unconfirmed responses based on BICR.
  • Best Objective Response (BoR) [ Time Frame: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months). ]
    The BoR was calculated based on the overall visit responses from each RECIST 1.1 assessment. BOR was defined as the best response a patient had following randomization, but prior to starting any subsequent cancer therapy and up to and including RECIST 1.1 progression or the last evaluable assessment in the absence of RECIST 1.1 progression, as determined by BICR. Categorization of BoR was based on RECIST using the following 'response' categories: CR and PR and the following 'non-response' categories: stable disease (SD) ≥6 weeks, progression (ie, PD) and not evaluable (NE). Results are presented for number (%) of patients in each specified category.
  • Duration of Response (DoR) [ Time Frame: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months). ]
    DoR (per RECIST 1.1 using BICR assessments) was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. The end of response coincided with the date of progression or death from any cause used for the RECIST 1.1 PFS endpoint. The time of the initial response was defined as the latest of the dates contributing towards the first visit of PR or CR. Results are presented for the pre-specified DoR analysis using unconfirmed responses based on BICR.
  • Time From Randomization to Second Progression (PFS2) [ Time Frame: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months). ]
    PFS2 was defined as the time from the date of randomization to the earliest of the progression event (subsequent to that used for the primary variable PFS) or death. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of: objective radiological imaging, symptomatic progression or death.
  • Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations [ Time Frame: Samples were collected post-dose on Day 1 (Week 0), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021. ]
    To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.
  • PK of Tremelimumab; Peak and Trough Serum Concentrations [ Time Frame: Samples were collected post-dose on Day 1 (Week 0), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021. ]
    To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.
  • Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab [ Time Frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, durvalumab). ]
    Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against durvalumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of neutralizing antibody (nAb) was tested for all ADA positive samples.
  • Number of Patients With ADA Response to Tremelimumab [ Time Frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, tremelimumab). ]
    Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against tremelimumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples.
  • Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) [ Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months). ]
    The EORTC QLQ-Core 30 version 3 (QLQ-C30 v3) was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration was defined as time from randomization until the date of first clinically meaningful deterioration that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.
  • Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13) [ Time Frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months). ]
    The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration was defined as time from randomization until the date of first clinically meaningful deterioration that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2017)
  • Progression-free survival (PFS) using BICR assessments according to RECIST 1.1 [ Time Frame: Up to 3 years after first patient randomized ]
  • Overall survival (OS) [ Time Frame: Up to 4 years after first patient randomized ]
  • Objective response rate (ORR) using BICR assessments according to RECIST 1.1 [ Time Frame: Up to 3 years after first patient randomized ]
  • Duration of response (DoR) using BICR assessments according to RECIST 1.1 [ Time Frame: Up to 3 years after first patient randomized ]
  • Time from randomization to second progression (PFS2) [ Time Frame: Up to 3 years after first patient randomized ]
  • Proportion of patients alive and progression free at 12 months from randomization (APF12) using BICR assessments according to RECIST 1.1 [ Time Frame: Up to 12 months ]
  • Best objective response (BoR) using BICR assessments according to RECIST 1.1 [ Time Frame: Up to 3 years after first patient randomized ]
  • The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by concentration [ Time Frame: Up to 3 years after first patient randomized ]
  • The immunogenicity of durvalumab and tremelimumab as assessed by presence of anti-drug antibodies (ADAs) [ Time Frame: Up to 3 years after first patient randomized ]
  • Health-related QoL measured by EORTC QLQ-C30 v3 [ Time Frame: Up to 3 years after first patient randomized ]
  • Disease-related symptoms measured by EORTC QLQ-LC13 [ Time Frame: Up to 3 years after first patient randomized ]
  • Changes in WHO/ECOG performance status [ Time Frame: Up to 3 years after first patient randomized ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 22, 2017)
The safety and tolerability profile of durvalumab +/- tremelimumab in combination with standard of care chemotherapy as determined by adverse events (AEs), physical examninations, laboratory data and vital signs [ Time Frame: Up to 3 years ]
 
Descriptive Information
Brief Title  ICMJE Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON).
Official Title  ICMJE A Phase III, Randomized, Multi-Center, Open-Label, Comparative Global Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Patients With Metastatic Non Small-Cell Lung Cancer (NSCLC) (POSEIDON)
Brief Summary This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy + Standard of care (SoC) chemotherapy or durvalumab monotherapy + SoC chemotherapy versus SoC chemotherapy alone as first line treatment in patients with metastatic non small-cell lung cancer (NSCLC) with tumors that lack activating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions.
Detailed Description Adult patients with a histologically or cytologically documented metastatic NSCLC, with tumors that lack activating EGFR mutations and ALK fusions, are eligible for enrollment. Patients will be randomized in a 1:1:1 ratio to receive treatment with durvalumab + tremelimumab combination therapy + SoC chemotherapy, durvalumab monotherapy + SoC chemotherapy, or SoC chemotherapy alone. Tumor evaluation scans will be performed until objective disease progression as efficacy assessment. All patients will be followed for survival until the end of the study. An independent data monitoring committee (IDMC) composed of independent experts will be convened to confirm the safety and tolerability of the proposed dose and schedule.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Cancer NSCLC
Intervention  ICMJE
  • Drug: Durvalumab
    IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until disease progression or other discontinuation criteria
  • Drug: Tremelimumab
    IV infusions every 3 weeks for 12 weeks (4 cycles). An additional dose of tremelimumab will be administered in the week 16.
  • Drug: Abraxane + carboplatin
    Standard of care chemotherapy (squamous and non-squamous patients): Abraxane 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Carboplatin Area under the plasma drug concentration-time curve (AUC) 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).
  • Drug: Gemcitabine + cisplatin
    Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).
  • Drug: Gemcitabine + carboplatin
    Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).
  • Drug: Pemetrexed + carboplatin
    Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.
  • Drug: Pemetrexed + cisplatin
    Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.
Study Arms  ICMJE
  • Experimental: Treatment Arm 1
    durvalumab + tremelimumab combination therapy + SoC chemotherapy
    Interventions:
    • Drug: Durvalumab
    • Drug: Tremelimumab
    • Drug: Abraxane + carboplatin
    • Drug: Gemcitabine + cisplatin
    • Drug: Gemcitabine + carboplatin
    • Drug: Pemetrexed + carboplatin
    • Drug: Pemetrexed + cisplatin
  • Experimental: Treatment Arm 2
    durvalumab monotherapy + SoC chemotherapy
    Interventions:
    • Drug: Durvalumab
    • Drug: Abraxane + carboplatin
    • Drug: Gemcitabine + cisplatin
    • Drug: Gemcitabine + carboplatin
    • Drug: Pemetrexed + carboplatin
    • Drug: Pemetrexed + cisplatin
  • Active Comparator: Treatment Arm 3
    SoC chemotherapy alone
    Interventions:
    • Drug: Abraxane + carboplatin
    • Drug: Gemcitabine + cisplatin
    • Drug: Gemcitabine + carboplatin
    • Drug: Pemetrexed + carboplatin
    • Drug: Pemetrexed + cisplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 27, 2020)
1193
Original Estimated Enrollment  ICMJE
 (submitted: May 22, 2017)
801
Estimated Study Completion Date  ICMJE February 28, 2025
Actual Primary Completion Date March 12, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

  1. Aged at least 18 years.
  2. Histologically or cytologically documented Stage IV NSCLC.
  3. Confirmed tumor PD-L1 status prior to randomization.
  4. Patients must have tumors that lack activating EGFR mutations and ALK fusions.
  5. No prior chemotherapy or any other systemic therapy for metastatic NSCLC.
  6. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. No prior exposure to immunemediated therapy, excluding therapeutic anticancer vaccines.

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. Active or prior documented autoimmune or inflammatory disorders.
  3. Brain metastases or spinal cord compression unless the patient's condition is stable and off steroids.
  4. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service 1-877-400-4656 AstraZeneca@emergingmed.com
Listed Location Countries  ICMJE Brazil,   Bulgaria,   China,   Germany,   Hong Kong,   Hungary,   Japan,   Korea, Republic of,   Mexico,   Peru,   Poland,   Russian Federation,   South Africa,   Taiwan,   Thailand,   Ukraine,   United Kingdom,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03164616
Other Study ID Numbers  ICMJE D419MC00004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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 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 Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
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 refer 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 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
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Current Responsible Party AstraZeneca
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Xiaojin Shi, M.D., MSc One MedImmune Way, Gaithersburg, Maryland 20878, United States
PRS Account AstraZeneca
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP