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Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Resectable Non-Small Cell Lung Cancer

Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT03794544
Collaborator
(none)
84
Enrollment
18
Locations
4
Arms
22.2
Actual Duration (Months)
4.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study D9108C00002 (NeoCOAST) is a platform study assessing the effectiveness and safety of neoadjuvant durvalumab alone or in combination with novel agents in participants with resectable, early-stage (Stage I [>2cm] to IIIA) non-small cell lung cancer (NSCLC).

Condition or Disease Intervention/Treatment Phase
  • Drug: Durvalumab
  • Combination Product: Oleclumab
  • Combination Product: Monalizumab
  • Combination Product: Danvatirsen
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
84 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Participants will be enrolled and randomized into a durvalumab monotherapy arm or into a durvalumab plus other novel therapy arms. Up to approximately 25 sites globally will participate in this study. New treatment arms may be added in the future. Participants will be treated with a single durvalumab dose alone or in combination with other agents. After the single cycle treatment period participants will have the standard surgical resection planned. All participants will have a post-resection monitoring visit. Study treatment will be discontinued upon disease progression, unacceptable toxicity, or other investigators' reasons.Participants will be enrolled and randomized into a durvalumab monotherapy arm or into a durvalumab plus other novel therapy arms. Up to approximately 25 sites globally will participate in this study. New treatment arms may be added in the future. Participants will be treated with a single durvalumab dose alone or in combination with other agents. After the single cycle treatment period participants will have the standard surgical resection planned. All participants will have a post-resection monitoring visit. Study treatment will be discontinued upon disease progression, unacceptable toxicity, or other investigators' reasons.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Open-label, Multicenter, Randomized, Multidrug Platform Study of Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Subjects With Resectable, Early-stage (I [> 2 cm] to IIIA) Non-small Cell Lung Cancer (NeoCOAST)
Actual Study Start Date :
Mar 8, 2019
Actual Primary Completion Date :
Jan 13, 2021
Actual Study Completion Date :
Jan 13, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Durvalumab 1500 mg

Participants will receive durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).

Drug: Durvalumab
Durvalumab 1500 mg IV will be administered Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
Other Names:
  • MEDI4736

    		•
    Experimental: Durvalumab 1500 mg + Oleclumab 3000 mg

    Participants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).

    Drug: Durvalumab
    Durvalumab 1500 mg IV will be administered Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
    Other Names:
  • MEDI4736

    • Combination Product: Oleclumab
    Oleclumab 3000 mg IV will be administered Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
    Other Names:
  • MEDI9447

    		•
    Experimental: Durvalumab 1500 mg + Monalizumab 750 mg

    Participants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).

    Drug: Durvalumab
    Durvalumab 1500 mg IV will be administered Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
    Other Names:
  • MEDI4736

    • Combination Product: Monalizumab
    Monalizumab 750 mg IV will be administered Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
    Other Names:
  • IPH2201

    		•
    Experimental: Durvalumab 1500 mg + Danvatirsen 200 mg

    Participants will receive danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).

    Drug: Durvalumab
    Durvalumab 1500 mg IV will be administered Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
    Other Names:
  • MEDI4736

    • Combination Product: Danvatirsen
    Danvatirsen 200 mg IV will be administered on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period) and later every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
    Other Names:
  • AZD9150

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Major Pathological Response Rate [Day 1 through Day 42]

      Major pathological response rate is defined as percentage of participants with <=10% residual viable tumor cells in the resected specimen.

    Secondary Outcome Measures

    1. Pathological Complete Response (pCR) Rate [Day 1 through Day 42]

      The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen.

    2. Feasibility to Surgery [Day 29 to Day 42 after Week 1 Day 1]

      Feasibility to surgery is defined as the percentage of participants who underwent the planned surgery within Days 29 to 42 after Week 1 Day 1.

    3. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [From Day 1 through Day 105]

      An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

    4. Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities [From Day 1 through Day 105]

      Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis.

    5. Number of Participants With Abnormal Vital Signs Reported as TEAEs [From Day 1 through Day 105]

      Participants with abnormal vital sign reported as TEAEs are reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 102 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Cytologically and/or histologically-documented NSCLC

    2. Stage I (> 2 cm) to IIIA (for participants with N2 disease, only those with 1 single nodal station ≤ 3 cm are eligible) NSCLC according to the 8th edition of American Joint Committee on Cancer staging classification

    3. Amenable to complete surgical resection

    4. Have not received any other therapy for this condition

    5. Predicted forced expiratory volume in one second (FEV1) ≥ 50%

    6. Predicted diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50%

    7. ECOG 0 or 1

    8. Adequate organ function

    Exclusion Criteria:

    1. Participants with small-cell lung cancer or mixed small-cell lung cancer

    2. Participants who require or may require pneumonectomy

    3. Prior treatment with programmed cell death ligand-1 (PD-L1), PD-L1, or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors

    4. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug.

    5. Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion:

    6. Participants with vitiligo or alopecia

    7. Participants with hypothyroidism on hormone replacement

    8. Any chronic skin condition that does not require systemic therapy

    9. Participants without active disease in the last 5 years may be included but only after consultation with the study physician

    10. Participants with celiac disease controlled by diet alone

    11. Pregnant or breast-feeding female

    12. Major surgical procedure within prior 30 days

    13. History of active primary immunodeficiency

    14. Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV

    15. QTc interval (QTc) ≥ 470 ms

    16. Uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent

    17. Receipt of live attenuated vaccination within 30 days prior to study entry

    18. History of another primary malignancy except for:

    19. Curative-treated malignancy with no known active disease > 2 years before enrollment on the study

    20. Curative-treated non-melanoma skin cancer and/or carcinoma in-situ

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site La Jolla California United States 92093
    2 Research Site Fort Myers Florida United States 33901
    3 Research Site Leesburg Florida United States 34748
    4 Research Site Baltimore Maryland United States 21231
    5 Research Site Buffalo New York United States 14263
    6 Research Site New York New York United States 10016
    7 Research Site Chattanooga Tennessee United States 37404
    8 Research Site Nashville Tennessee United States 37203
    9 Research Site Houston Texas United States 77030
    10 Research Site Fairfax Virginia United States 22031
    11 Research Site Montreal Quebec Canada H4A 3J1
    12 Research Site Marseille Cedex 9 France 13009
    13 Research Site Toulouse CEDEX 09 France 31059
    14 Research Site Orbassano Italy 10043
    15 Research Site Porto Portugal 4200-072
    16 Research Site A Coruña Spain 15001
    17 Research Site Barcelona Spain 08916
    18 Research Site Zurich Switzerland 8091

    Sponsors and Collaborators

    • MedImmune LLC

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT03794544
    Other Study ID Numbers:
    • D9108C00002
    First Posted:
    Jan 7, 2019
    Last Update Posted:
    Feb 24, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by MedImmune LLC
    Neoadjuvant
    Non-small Cell Lung Cancer
    Cancer
    Lung
    Resectable
    Early-stage
    Stage I
    Stage II
    Stage IIIA
    Durvalumab
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Durvalumab

    Study Results

    Participant Flow

    Recruitment Details The trial was interrupted due to COVID-19 pandemic from 13Apr2020 to 07May2020.
    Pre-assignment Detail
    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Period Title: Overall Study
    STARTED 27 21 20 16
    Treated 26 21 20 16
    COMPLETED 26 18 19 15
    NOT COMPLETED 1 3 1 1

    Baseline Characteristics

    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg Total
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Total of all reporting groups
    Overall Participants 27 21 20 16 84
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    67.1
    (9.0)
    65.5
    (7.5)
    65.1
    (6.3)
    72.9
    (7.9)
    67.3
    (8.2)
    Sex: Female, Male (Count of Participants)
    Female
    13
    48.1%
    9
    42.9%
    6
    30%
    6
    37.5%
    34
    40.5%
    Male
    14
    51.9%
    12
    57.1%
    14
    70%
    10
    62.5%
    50
    59.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    3.7%
    0
    0%
    0
    0%
    2
    12.5%
    3
    3.6%
    Not Hispanic or Latino
    26
    96.3%
    21
    100%
    20
    100%
    14
    87.5%
    81
    96.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    3.7%
    0
    0%
    0
    0%
    1
    6.3%
    2
    2.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    3
    11.1%
    1
    4.8%
    1
    5%
    0
    0%
    5
    6%
    White
    23
    85.2%
    20
    95.2%
    19
    95%
    13
    81.3%
    75
    89.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    2
    12.5%
    2
    2.4%

    Outcome Measures

    1. Primary Outcome
    Title Major Pathological Response Rate
    Description Major pathological response rate is defined as percentage of participants with <=10% residual viable tumor cells in the resected specimen.
    Time Frame Day 1 through Day 42

    Outcome Measure Data

    Analysis Population Description
    The ITT population included participants who were randomized and were analyzed according to their randomized treatment group.
    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Measure Participants 27 21 20 16
    Number (95% Confidence Interval) [Percentage of participants]
    11.1
    41.1%
    19.0
    90.5%
    30.0
    150%
    31.3
    195.6%
    2. Secondary Outcome
    Title Pathological Complete Response (pCR) Rate
    Description The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen.
    Time Frame Day 1 through Day 42

    Outcome Measure Data

    Analysis Population Description
    The ITT population included participants who were randomized and were analyzed according to their randomized treatment group.
    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Measure Participants 27 21 20 16
    Number (95% Confidence Interval) [Percentage of participants]
    3.7
    13.7%
    9.5
    45.2%
    10.0
    50%
    12.5
    78.1%
    3. Secondary Outcome
    Title Feasibility to Surgery
    Description Feasibility to surgery is defined as the percentage of participants who underwent the planned surgery within Days 29 to 42 after Week 1 Day 1.
    Time Frame Day 29 to Day 42 after Week 1 Day 1

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Measure Participants 26 21 20 16
    Number [Percentage of participants]
    84.6
    313.3%
    81.0
    385.7%
    90.0
    450%
    93.8
    586.3%
    4. Secondary Outcome
    Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
    Description An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
    Time Frame From Day 1 through Day 105

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Measure Participants 26 21 20 16
    Any TEAEs
    18
    66.7%
    19
    90.5%
    15
    75%
    13
    81.3%
    Any TESAEs
    3
    11.1%
    2
    9.5%
    1
    5%
    5
    31.3%
    5. Secondary Outcome
    Title Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities
    Description Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis.
    Time Frame From Day 1 through Day 105

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. 'Number Analyzed' denotes the participants analyzed for the specified laboratory parameters.
    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Measure Participants 26 21 20 16
    Alanine aminotransferase increased
    0
    0%
    0
    0%
    0
    0%
    2
    12.5%
    Gamma glutamyl transferase increased
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    Lipase increased
    1
    3.7%
    1
    4.8%
    1
    5%
    0
    0%
    Hyponatremia
    2
    7.4%
    0
    0%
    0
    0%
    0
    0%
    Lymphocyte count decreased
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    6. Secondary Outcome
    Title Number of Participants With Abnormal Vital Signs Reported as TEAEs
    Description Participants with abnormal vital sign reported as TEAEs are reported.
    Time Frame From Day 1 through Day 105

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Measure Participants 26 21 20 16
    Palpitations
    1
    3.7%
    0
    0%
    0
    0%
    0
    0%
    Pyrexia
    1
    3.7%
    2
    9.5%
    1
    5%
    0
    0%

    Adverse Events

    Time Frame From Day 1 through Day 105
    Adverse Event Reporting Description As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
    Arm/Group Title Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm/Group Description Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1). Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    All Cause Mortality
    Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/26 (0%) 0/21 (0%) 0/20 (0%) 1/16 (6.3%)
    Serious Adverse Events
    Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/26 (11.5%) 2/21 (9.5%) 1/20 (5%) 5/16 (31.3%)
    Cardiac disorders
    Pericarditis 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Infections and infestations
    Covid-19 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Pneumonia 1/26 (3.8%) 1 1/21 (4.8%) 1 0/20 (0%) 0 1/16 (6.3%) 1
    Wound infection 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Injury, poisoning and procedural complications
    Bronchial anastomosis complication 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Procedural haemorrhage 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Metabolism and nutrition disorders
    Diabetic ketoacidosis 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Musculoskeletal and connective tissue disorders
    Immune-mediated arthritis 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Renal and urinary disorders
    Renal infarct 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Haemothorax 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Pleural effusion 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Pneumothorax 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Pulmonary air leakage 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Other (Not Including Serious) Adverse Events
    Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 18/26 (69.2%) 19/21 (90.5%) 14/20 (70%) 13/16 (81.3%)
    Blood and lymphatic system disorders
    Anaemia 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Nephrogenic anaemia 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Neutropenia 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Thrombocytopenia 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Cardiac disorders
    Atrial fibrillation 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Palpitations 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Endocrine disorders
    Hypothyroidism 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Eye disorders
    Vision blurred 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Visual impairment 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Vitreous floaters 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Gastrointestinal disorders
    Constipation 1/26 (3.8%) 1 1/21 (4.8%) 1 2/20 (10%) 2 0/16 (0%) 0
    Diarrhoea 1/26 (3.8%) 1 2/21 (9.5%) 2 0/20 (0%) 0 0/16 (0%) 0
    Dyspepsia 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Gastrooesophageal reflux disease 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 2/16 (12.5%) 2
    Haemorrhoids 2/26 (7.7%) 2 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Nausea 2/26 (7.7%) 2 3/21 (14.3%) 3 0/20 (0%) 0 1/16 (6.3%) 1
    Oral pain 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Stomatitis 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Toothache 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Vomiting 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    General disorders
    Asthenia 3/26 (11.5%) 3 3/21 (14.3%) 3 0/20 (0%) 0 0/16 (0%) 0
    Chills 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Facial pain 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Fatigue 6/26 (23.1%) 6 4/21 (19%) 4 2/20 (10%) 2 3/16 (18.8%) 3
    Generalised oedema 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Non-cardiac chest pain 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Oedema peripheral 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 2
    Pyrexia 1/26 (3.8%) 1 2/21 (9.5%) 2 1/20 (5%) 1 0/16 (0%) 0
    Immune system disorders
    Seasonal allergy 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Infections and infestations
    Covid-19 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Chest wall abscess 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Herpes zoster 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Influenza 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Pneumonia 1/26 (3.8%) 1 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Upper respiratory tract infection 0/26 (0%) 0 1/21 (4.8%) 1 2/20 (10%) 2 0/16 (0%) 0
    Urinary tract infection 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Injury, poisoning and procedural complications
    Fall 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Post procedural discomfort 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Procedural pain 5/26 (19.2%) 5 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Investigations
    Alanine aminotransferase increased 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 2/16 (12.5%) 2
    Amylase increased 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Aspartate aminotransferase increased 1/26 (3.8%) 1 1/21 (4.8%) 1 0/20 (0%) 0 1/16 (6.3%) 1
    Blood alkaline phosphatase increased 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Blood bicarbonate decreased 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Blood bilirubin increased 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Blood creatinine increased 1/26 (3.8%) 1 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Blood lactate dehydrogenase increased 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Blood thyroid stimulating hormone decreased 0/26 (0%) 0 2/21 (9.5%) 2 0/20 (0%) 0 0/16 (0%) 0
    Gamma-glutamyltransferase increased 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Hepatic enzyme increased 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    International normalised ratio decreased 0/26 (0%) 0 1/21 (4.8%) 1 1/20 (5%) 1 1/16 (6.3%) 1
    Lymphocyte count decreased 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Neutrophil count decreased 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Platelet count decreased 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Prothrombin time shortened 0/26 (0%) 0 1/21 (4.8%) 1 1/20 (5%) 1 1/16 (6.3%) 1
    Transaminases increased 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Tri-iodothyronine increased 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Weight decreased 0/26 (0%) 0 2/21 (9.5%) 2 0/20 (0%) 0 0/16 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 3/26 (11.5%) 3 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Diabetes mellitus 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Hyperkalaemia 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Hypoalbuminaemia 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Hypokalaemia 1/26 (3.8%) 1 2/21 (9.5%) 2 1/20 (5%) 1 0/16 (0%) 0
    Hypomagnesaemia 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Hyponatraemia 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/26 (7.7%) 2 2/21 (9.5%) 2 0/20 (0%) 0 0/16 (0%) 0
    Back pain 1/26 (3.8%) 1 0/21 (0%) 0 1/20 (5%) 1 1/16 (6.3%) 1
    Bone pain 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Chest wall mass 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Joint swelling 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Muscle tightness 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Muscular weakness 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Musculoskeletal chest pain 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Musculoskeletal pain 2/26 (7.7%) 2 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Myalgia 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Neck pain 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Osteoarthritis 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Nervous system disorders
    Dizziness 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Dysgeusia 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Headache 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Paraesthesia 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 2/16 (12.5%) 2
    Peripheral sensory neuropathy 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Sciatica 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Syncope 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Transient ischaemic attack 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Vocal cord paresis 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Psychiatric disorders
    Anxiety 2/26 (7.7%) 2 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Depression 2/26 (7.7%) 2 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Emotional distress 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Insomnia 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Renal and urinary disorders
    Urinary retention 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 1/26 (3.8%) 1 3/21 (14.3%) 3 1/20 (5%) 1 2/16 (12.5%) 2
    Dyspnoea 3/26 (11.5%) 3 1/21 (4.8%) 1 0/20 (0%) 0 3/16 (18.8%) 3
    Epistaxis 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Haemoptysis 0/26 (0%) 0 1/21 (4.8%) 1 1/20 (5%) 1 0/16 (0%) 0
    Nasal congestion 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Nasal obstruction 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Pneumonitis 1/26 (3.8%) 1 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Productive cough 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Rhinitis allergic 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 1/16 (6.3%) 1
    Skin and subcutaneous tissue disorders
    Dermatitis 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Dry skin 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 1/16 (6.3%) 1
    Erythema 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Onychoclasis 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Pruritus 0/26 (0%) 0 2/21 (9.5%) 2 2/20 (10%) 2 2/16 (12.5%) 2
    Rash 0/26 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/16 (0%) 0
    Rash maculo-papular 1/26 (3.8%) 1 1/21 (4.8%) 1 1/20 (5%) 1 1/16 (6.3%) 1
    Rash pruritic 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Scar pain 0/26 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/16 (0%) 0
    Skin discolouration 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1
    Vascular disorders
    Embolism 1/26 (3.8%) 1 0/21 (0%) 0 0/20 (0%) 0 0/16 (0%) 0
    Hot flush 0/26 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/16 (6.3%) 1

    Limitations/Caveats

    The pharmacokinetic and immunogenicity samples are still being analyzed. Results for these outcome measures will be posted by 30Jun2022.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

    Results Point of Contact

    Name/Title Global Clinical Lead
    Organization AstraZeneca Clinical Study Information Center
    Phone 1-877-240-9479
    Email information.center@astrazeneca.com
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT03794544
    Other Study ID Numbers:
    • D9108C00002
    First Posted:
    Jan 7, 2019
    Last Update Posted:
    Feb 24, 2022
    Last Verified:
    Feb 1, 2022