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An Open-label, Phase II Study of AZD4635 in Patients With Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04089553
Recruitment Status : Active, not recruiting
First Posted : September 13, 2019
Results First Posted : July 8, 2022
Last Update Posted : January 13, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Interventions Drug: AZD4635
Drug: Oleclumab
Drug: Durvalumab
Enrollment 59
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first. Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Period Title: Overall Study
Started 29 30
Completed 4 12
Not Completed 25 18
Reason Not Completed
Death             12             11
Lost to Follow-up             2             2
Progressive disease             0             1
Withdrawal by Subject             5             2
Other             6             2
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg) Total
Hide Arm/Group Description Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first. Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first. Total of all reporting groups
Overall Number of Baseline Participants 29 30 59
Hide Baseline Analysis Population Description
Safety analysis set included all participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 30 participants 59 participants
72.2  (7.10) 72.7  (7.33) 72.5  (7.16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 30 participants 59 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
29
 100.0%
30
 100.0%
59
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 30 participants 59 participants
Hispanic or Latino
4
  13.8%
2
   6.7%
6
  10.2%
Not Hispanic or Latino
24
  82.8%
28
  93.3%
52
  88.1%
Unknown or Not Reported
1
   3.4%
0
   0.0%
1
   1.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 30 participants 59 participants
American Indian or Alaska Native
0
   0.0%
1
   3.3%
1
   1.7%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
  17.2%
3
  10.0%
8
  13.6%
White
23
  79.3%
24
  80.0%
47
  79.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   3.4%
2
   6.7%
3
   5.1%
1.Primary Outcome
Title Percentage of Participants With Confirmed Objective Response Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Hide Description The confirmed objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines, assessed by computed tomography (CT) scan/ magnetic resonance imaging (MRI) scan/ positron emission tomography (PET) scan and bone scan. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.
Time Frame Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Tumor response analysis set included all participants who received at least one dose of study drug and had a baseline tumor assessment and measurable disease at baseline.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 20 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
5
(0.1 to 24.9)
0 [1] 
(NA to 16.1)
[1]
Lower limit of 95% CI was not reached because an insufficient number of participants had objective response.
2.Primary Outcome
Title Percentage of Participants With Confirmed Prostate-specific Antigen (PSA) Response Per Prostate Cancer Working Group 3 (PCWG3) Criteria
Hide Description A confirmed PSA response is defined as reduction in the PSA level of >= 50% from baseline to the lowest post-baseline PSA results, measured twice, at least 3 weeks apart by the PCWG3 criteria.
Time Frame Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The PSA response analysis set included all participants who received at least one dose of study drug and had an abnormal baseline PSA data (>= 1 ng/mL).
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 28 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
3.6
(0.1 to 18.3)
3.3
(0.1 to 17.2)
3.Secondary Outcome
Title Percentage of Participants With Radiological Progression Free Survival (rPFS) at 6 Months
Hide Description The rPFS is defined as the time interval from the first dose of AZD4635 until the date of radiological disease progression (RECIST 1.1 for soft tissue lesions and PCWG3 criteria for bone lesions) or death (by any cause in the absence of progression) regardless of whether the participant withdrew from study therapy or received another anti-cancer therapy prior to progression. The progressive disease for soft lesions per RECIST 1.1 (assessed by CT/MRI/PET scan) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum in the study, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The progressive disease for bone lesions per PCWG3 is defined as at least 2 or more new metastatic bone lesions observed compared to baseline assessment (Day -28), with confirmation scan performed at least 6-week later.
Time Frame Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis set included all participants who received at least one dose of study drug and had a baseline tumor assessment.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 29 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
8.8
(0.71 to 30.28)
11.1
(2.83 to 25.75)
4.Secondary Outcome
Title Duration of Response (DoR)
Hide Description The DoR is defined as the time from the date of first documented response (confirmed CR/PR) until date of documented progression or death in the absence of disease progression. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. The progressive disease is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The DoR was estimated using Kaplan-Meier method.
Time Frame Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Tumor response analysis set included all participants who received at least one dose of study drug and had a baseline tumor assessment (Day -28) and measurable disease at baseline. Participants who had confirmed CR/PR were analyzed for this outcome measure.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 1 0
Median (Inter-Quartile Range)
Unit of Measure: Months
NA [1] 
(NA to NA)
[1]
Median and inter-quartile range could not be determined because insufficient number of participants were evaluated for the specified arm.
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description The OS is defined as the time from date of first study dose until the date of death due to any cause. The median of OS was estimated using Kaplan-Meier method and CI was derived based on Brookmeyer-Crowley method.
Time Frame Baseline (Day -28) through end of study (last participant last visit) (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 29 30
Median (95% Confidence Interval)
Unit of Measure: Months
10.72 [1] 
(7.20 to NA)
NA [2] 
(10.65 to NA)
[1]
Upper limit of 95% CI was not determined because an insufficient number of participants had events.
[2]
Median and upper limit of 95% CI were not determined because an insufficient number of participants had events.
6.Secondary Outcome
Title Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab
Hide Description The detection of the immunogenicity of monoclonal antibody to durvalumab was performed using a validated immunoassay method. Participants with positive ADA to durvalumab are reported.
Time Frame Pre-dose on Day 1 of Cycles 1, 2, 4, and 7 and 90 days following the last dose of durvalumab (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of durvalumab and had at least one post dose ADA sample.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
4
  15.4%
7.Secondary Outcome
Title Number of Participants With Positive ADA to Oleclumab
Hide Description The detection of the immunogenicity of monoclonal antibody to oleclumab was performed using a validated immunoassay method. Participants with positive ADA to oleclumab are reported.
Time Frame Pre-dose on Day 1 of Cycles 1, 3, 5, and every 12 weeks thereafter, and 90 days following the last dose of oleclumab (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of oleclumab and had at least one post dose ADA sample.
Arm/Group Title Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
1
   4.2%
8.Secondary Outcome
Title Plasma Concentrations of AZD4635 and Its Metabolites (SSP-005173 and SSP-005174)
Hide Description Plasma concentrations of AZD4635 and its metabolites (SSP-005173 and SSP-005174) are reported.
Time Frame Predose on Day 1 of Cycle 7
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics (PK) analysis set included all participants who received at least one dose of AZD4635 and had at least 1 reportable PK concentration at Cycle 7.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 3 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
AZD4635 concentration
97.64
(21.67%)
75.47
(83.37%)
SSP-005173 concentration
5.386
(95.48%)
6.905
(160.2%)
SSP-005174 concentration
13.24
(69.59%)
11.79
(75.23%)
9.Secondary Outcome
Title Plasma Concentration of Durvalumab
Hide Description Plasma concentration of durvalumab is reported.
Time Frame Predose and end of infusion on Day 1 of Cycle 7
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set included all participants who received at least one dose of durvalumab and had at least 1 reportable PK concentration at Cycle 7. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Pre-dose Number Analyzed 2 participants
NA [1] 
(NA%)
End of infusion Number Analyzed 1 participants
NA [2] 
(NA%)
[1]
Geometric mean and geometric coefficient of variation were not reported as an insufficient participants were evaluated for the specified time point.
[2]
Geometric mean and geometric coefficient of variation were not reported as only one participant was evaluated for the specified time point.
10.Secondary Outcome
Title Plasma Concentration of Oleclumab
Hide Description Plasma concentration of oleclumab is reported.
Time Frame Predose and 10 minutes end of infusion on Day 1 of Cycle 14
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set included all participants who received at least one dose of oleclumab and had at least 1 reportable PK concentration at Cycle 7. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
Arm/Group Title Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
Pre-dose
NA [1] 
(NA%)
10 minutes end of infusion
NA [1] 
(NA%)
[1]
Geometric mean and geometric coefficient of variation were not reported as only one participant was evaluated for the specified time point.
11.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Hide Description An 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 Day 1 through 90 days after the last dose of study drug (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 29 30
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
27
  93.1%
29
  96.7%
Any TESAEs
6
  20.7%
8
  26.7%
12.Secondary Outcome
Title Number of Participants With Common Terminology Criteria for Adverse Events (CTCAE) Grade Change in Laboratory Parameters From Baseline to Grade 3 or More
Hide Description Laboratory parameters included hematology, coagulation, clinical chemistry, and urinalysis. The CTCAE is a descriptive terminology is used for AE reporting. The CTCAE v5.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death related to AE. Participants with CTCAE v5.0 grade change in laboratory parameters from baseline (Day 1 before the start of study treatment) to Grade 3 or more are reported.
Time Frame Baseline (Day 1) through 90 days after the last dose of study drug (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 29 30
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin (low)
2
   6.9%
2
   6.7%
Leukocytes (low)
0
   0.0%
1
   3.3%
Lymphocytes (low)
4
  13.8%
6
  20.0%
Albumin
1
   3.4%
0
   0.0%
Alkaline Phosphatase
1
   3.4%
0
   0.0%
Gamma Glutamyl Transferase
1
   3.4%
0
   0.0%
Lipase
3
  10.3%
1
   3.3%
Sodium (low)
1
   3.4%
1
   3.3%
13.Secondary Outcome
Title Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs
Hide Description Vital signs assessment included body temperature, respiration rate, pulse rate, blood pressure, and weight. Participants with abnormal vital signs and/or abnormal physical examination reported as TEAEs are reported.
Time Frame Day 1 through 90 days after the last dose of study drug (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description:
Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
Overall Number of Participants Analyzed 29 30
Measure Type: Count of Participants
Unit of Measure: Participants
Cachexia
1
   3.4%
1
   3.3%
Hypertension
1
   3.4%
2
   6.7%
Hypotension
0
   0.0%
1
   3.3%
Gait disturbance
0
   0.0%
1
   3.3%
Pyrexia
0
   0.0%
2
   6.7%
Time Frame Day 1 through 90 days after the last dose of study drug (approximately 22 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Hide Arm/Group Description Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first. Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.
All-Cause Mortality
Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Affected / at Risk (%) Affected / at Risk (%)
Total   12/29 (41.38%)      11/30 (36.67%)    
Hide Serious Adverse Events
Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/29 (20.69%)      8/30 (26.67%)    
Cardiac disorders     
Cardiac arrest  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Ischaemic cardiomyopathy  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Myocardial infarction  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Gastrointestinal disorders     
Abdominal pain  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Gastrointestinal haemorrhage  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Pancreatitis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Hepatobiliary disorders     
Cholecystitis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Infections and infestations     
Covid-19  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Urinary tract infection  1  2/29 (6.90%)  2 0/30 (0.00%)  0
Injury, poisoning and procedural complications     
Hip fracture  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  1/29 (3.45%)  2 0/30 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of colon  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Nervous system disorders     
Spinal cord compression  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Renal and urinary disorders     
Acute kidney injury  1  1/29 (3.45%)  2 0/30 (0.00%)  0
Haematuria  1  1/29 (3.45%)  1 2/30 (6.67%)  2
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Pneumonitis  1  1/29 (3.45%)  1 0/30 (0.00%)  0
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Module 1 (AZD4635 75 mg + Durvalumab 1500 mg) Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/29 (93.10%)      28/30 (93.33%)    
Blood and lymphatic system disorders     
Anaemia  1  3/29 (10.34%)  3 3/30 (10.00%)  3
Thrombocytopenia  1  0/29 (0.00%)  0 2/30 (6.67%)  2
Cardiac disorders     
Atrial fibrillation  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Sinus tachycardia  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Ear and labyrinth disorders     
Vertigo  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Eye disorders     
Eye pain  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Vitreous floaters  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Gastrointestinal disorders     
Abdominal discomfort  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Abdominal distension  1  0/29 (0.00%)  0 2/30 (6.67%)  2
Abdominal pain  1  3/29 (10.34%)  3 4/30 (13.33%)  4
Abdominal pain upper  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Constipation  1  4/29 (13.79%)  4 4/30 (13.33%)  5
Diarrhoea  1  4/29 (13.79%)  4 5/30 (16.67%)  5
Dyspepsia  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Eructation  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Gastrooesophageal reflux disease  1  1/29 (3.45%)  1 1/30 (3.33%)  1
Haemorrhoidal haemorrhage  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Haemorrhoids  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Nausea  1  13/29 (44.83%)  14 16/30 (53.33%)  19
Oral pain  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Vomiting  1  4/29 (13.79%)  9 7/30 (23.33%)  8
General disorders     
Asthenia  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Chills  1  2/29 (6.90%)  2 4/30 (13.33%)  4
Fatigue  1  7/29 (24.14%)  7 13/30 (43.33%)  13
Gait disturbance  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Infusion site extravasation  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Localised oedema  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Mucosal inflammation  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Non-cardiac chest pain  1  1/29 (3.45%)  1 2/30 (6.67%)  2
Oedema peripheral  1  3/29 (10.34%)  3 0/30 (0.00%)  0
Pain  1  2/29 (6.90%)  2 2/30 (6.67%)  2
Pyrexia  1  0/29 (0.00%)  0 2/30 (6.67%)  3
Hepatobiliary disorders     
Cholelithiasis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Hepatic pain  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Infections and infestations     
Cellulitis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Cystitis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Gingivitis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Rash pustular  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Respiratory tract infection  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Sinusitis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Skin infection  1  1/29 (3.45%)  1 1/30 (3.33%)  1
Tooth infection  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Urinary tract infection  1  4/29 (13.79%)  5 2/30 (6.67%)  6
Injury, poisoning and procedural complications     
Contusion  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Muscle injury  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Postoperative delirium  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Procedural pain  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Skin laceration  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  1/29 (3.45%)  1 1/30 (3.33%)  1
Amylase increased  1  1/29 (3.45%)  1 2/30 (6.67%)  2
Aspartate aminotransferase increased  1  1/29 (3.45%)  1 2/30 (6.67%)  2
Blood alkaline phosphatase increased  1  3/29 (10.34%)  3 0/30 (0.00%)  0
Blood creatinine increased  1  5/29 (17.24%)  5 1/30 (3.33%)  1
Blood lactate dehydrogenase increased  1  1/29 (3.45%)  1 0/30 (0.00%)  0
International normalised ratio increased  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Lipase increased  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Urine output decreased  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Weight decreased  1  1/29 (3.45%)  1 1/30 (3.33%)  1
Metabolism and nutrition disorders     
Cachexia  1  1/29 (3.45%)  1 1/30 (3.33%)  1
Decreased appetite  1  6/29 (20.69%)  6 8/30 (26.67%)  8
Dehydration  1  0/29 (0.00%)  0 4/30 (13.33%)  5
Hyperglycaemia  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Hyperkalaemia  1  1/29 (3.45%)  1 2/30 (6.67%)  2
Hyperphosphataemia  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Hyperuricaemia  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Hypocalcaemia  1  1/29 (3.45%)  1 1/30 (3.33%)  1
Hypokalaemia  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Hypomagnesaemia  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Vitamin b12 deficiency  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/29 (3.45%)  1 2/30 (6.67%)  3
Back pain  1  3/29 (10.34%)  3 4/30 (13.33%)  4
Bone pain  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Muscle spasms  1  2/29 (6.90%)  2 0/30 (0.00%)  0
Muscular weakness  1  3/29 (10.34%)  3 0/30 (0.00%)  0
Musculoskeletal chest pain  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Myalgia  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Pain in extremity  1  1/29 (3.45%)  1 1/30 (3.33%)  1
Tendonitis  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Nervous system disorders     
Dizziness  1  4/29 (13.79%)  4 2/30 (6.67%)  2
Dizziness postural  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Dysgeusia  1  0/29 (0.00%)  0 2/30 (6.67%)  2
Headache  1  0/29 (0.00%)  0 2/30 (6.67%)  2
Hypoaesthesia  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Metabolic encephalopathy  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Peripheral sensory neuropathy  1  2/29 (6.90%)  2 0/30 (0.00%)  0
Spinal cord compression  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Transient ischaemic attack  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Tremor  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Psychiatric disorders     
Agitation  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Anxiety  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Confusional state  1  2/29 (6.90%)  2 0/30 (0.00%)  0
Depression  1  0/29 (0.00%)  0 2/30 (6.67%)  2
Hallucination  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Insomnia  1  3/29 (10.34%)  3 2/30 (6.67%)  2
Renal and urinary disorders     
Chronic kidney disease  1  1/29 (3.45%)  2 1/30 (3.33%)  1
Dysuria  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Haematuria  1  0/29 (0.00%)  0 3/30 (10.00%)  4
Proteinuria  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Urinary retention  1  0/29 (0.00%)  0 2/30 (6.67%)  2
Reproductive system and breast disorders     
Prostatic pain  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/29 (3.45%)  1 4/30 (13.33%)  4
Dyspnoea  1  1/29 (3.45%)  1 3/30 (10.00%)  3
Epistaxis  1  0/29 (0.00%)  0 2/30 (6.67%)  3
Haemoptysis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Hypoxia  1  2/29 (6.90%)  2 0/30 (0.00%)  0
Nasal congestion  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Pneumothorax  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Pulmonary embolism  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Skin and subcutaneous tissue disorders     
Dermatitis  1  1/29 (3.45%)  1 0/30 (0.00%)  0
Hyperhidrosis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Pruritus  1  1/29 (3.45%)  1 1/30 (3.33%)  1
Rash  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Rash maculo-papular  1  1/29 (3.45%)  1 1/30 (3.33%)  2
Skin ulcer  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Vascular disorders     
Embolism  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Flushing  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Hot flush  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Hypertension  1  1/29 (3.45%)  2 2/30 (6.67%)  2
Hypotension  1  0/29 (0.00%)  0 1/30 (3.33%)  1
Thrombosis  1  0/29 (0.00%)  0 1/30 (3.33%)  1
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
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Name/Title: Global Clinical Lead
Organization: AstraZeneca Clinical Study Information Center
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04089553    
Other Study ID Numbers: D8731C00001
GU 156 ( Other Identifier: Sarah Cannon Development Innovations, LLC )
264471 ( Other Identifier: Parexel International (IRL) Limited )
First Submitted: August 29, 2019
First Posted: September 13, 2019
Results First Submitted: June 14, 2022
Results First Posted: July 8, 2022
Last Update Posted: January 13, 2023