Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
EGFR mutated, CD73, A2AR, Oleclumab, MEDI9447, AZD4635, Osimertinib, NSCLC, Immunotherapy
Brief summary
The objective of this study is to investigate the safety, tolerability, and antitumor activity of novel combination therapies administered in participants with advanced EGFRm NSCLC.
Interventions
BIOLOGICALOleclumab
Participants will receive oleclumab in combination with osimertinib or AZD4635 as stated in the arms' description.
DRUGOsimertinib
Participants will receive osimertinib in combination with oleclumab as stated in the arms' description.
DRUGAZD4635
Participants will receive AZD4635 in combination with oleclumab as stated in the arms' description.
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 101 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 3. Weight ≥ 35 kg 4. Diagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFRm * For Arm A (Oleclumab + Osimertinib arms): must have received 1 prior line of therapy with an EGFR tyrosine kinase inhibitor (TKI) and confirmed T790M negative * For Arm B (Oleclumab + AZD4635 arms): must have received at least 2 but not more than 4 prior lines of therapy.
Exclusion criteria
1. Receipt of an EGFR TKI within 14 days of the first dose of study treatment 2. Receipt of any conventional or investigational anticancer therapy not otherwise specified within 21 days of the planned first dose 3. Prior receipt of any investigational immunotherapy. Participants may have received agents that have local health authority approval for the disease indication 4. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed. 5. Participants with a history of venous thrombosis within the past 3 months 6. Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 6 months 7. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment 8. Other invasive malignancy within 2 years 9. Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression 10. Current or prior use of immunosuppressive medication within 14 days prior to the first dose Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1 | From Day 1 to Day 28 after first dose of study drug | A DLT was defined as \>= Grade 3 toxicity or adverse events (AE) occurred during DLT evaluation period which included any Grade 4 immune-mediated (immune nature) AE, anemia, thrombocytopenia (present \> 4 days), or neutropenia (present \> 4 days); \>= Grade 3 colitis or pneumonitis or interstitial lung disease (ILD); \>= Grade 3 nausea, vomiting, or diarrhea (not resolved to \<= Grade 2 in 3 days); Grade 2 pneumonitis or ILD (not resolved to \<= Grade 1 in 3 days); Grade 3 thrombocytopenia with bleeding, any grade febrile neutropenia; convulsions, seizures, or stroke; protocol defined elevations of isolated liver transaminase, isolated total bilirubin (TBL), or Hy's Law; confirmed QT interval corrected for heart rate by Fridericia's formula prolongation (\>= 501 msec) on triplicate electrocardiograms within a short period of time; or any other toxicity greater than that at baseline, was clinically significant and/or unacceptable, and was judged to be a DLT by the Dose Escalation Committee. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | 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. |
| Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, and urinalysis. |
| Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | Participants with abnormal vital signs (heart rate, blood pressure, temperature, and respiratory rate) and physical examination reported as TEAEs are reported. |
| Number of Participants With Notable QTc Interval in Parts 1 and 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | Notable QTc intervals included single beat changes from baseline (Day 1) values (\> 30, \> 60, and \> 90 milliseconds). Participants who had notable QTc interval are reported. |
| Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Part 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | The OR is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) Per RECIST v 1.1 for Parts 1 and 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | The DoR is defined as duration from the first documentation of OR (confirmed CR or PR) to the first documented disease progression based on RECIST v1.1 guidelines or death due to any cause, whichever occurs first. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no 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. The progressive disease is defined at least a 20% increase in sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The DoR was analyzed using Kaplan-Meier method. |
| Percentage of Participants With Disease Control (DC) in Parts 1 and 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | The DC is defined as percentage of participants with CR, PR, or stable disease (SD, which was maintained by \>= 8 week) based on RECIST v1.1 guidelines. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no non-target lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum longest diameter since the study treatment started, and non-progressive disease and not evaluable or no non-target lesion. |
| Progression Free Survival (PFS) for Parts 1 and 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | The PFS is defined as the time from the start of study treatment until the documentation of disease progression based on RECIST version 1.1 or death due to any cause, whichever occurs first, regardless of whether the participant received subsequent anticancer treatment prior to progression. 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. Participants who were alive and progression-free at the time of data cut-off for analysis had PFS censored at the last tumor assessment date. The PFS was estimated using Kaplan-Meier method. |
| Overall Survival (OS) for Parts 1 and 2 | From Day 1 through 90 days of the last dose of study drug (approximately 37 months) | The OS is defined as the time from the start of study treatment until death due to any cause. Participants who are alive at the time of data cut-off had OS censored at the last known to be alive date. The OS was estimated using Kaplan-Meier method. |
| Percentage of Participants With OR by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months) | The T790M status was determined by plasma testing in a central laboratory at Baseline (Days -28 to -1). The OR is defined as confirmed CR or confirmed PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no 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. Cell-free circulating tumor deoxyribonucleic acid (ctDNA) from liquid biopsy was used as a surrogate marker for T790M status in tumor tissue. |
| Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months) | The T790M status was determined by plasma testing in a central laboratory at Baseline (Days -28 to -1). The DC is defined as percentage of participants with CR, PR, or SD (maintained by \>= 8 week) based on RECIST v1.1 guidelines. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as \>= 30% decrease in the sum of longest diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no non-target lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum longest diameter since the study treatment started, and persistence of one or more non-target lesion(s). Cell-free circulating tumor deoxyribonucleic acid (ctDNA) from liquid biopsy was used as a surrogate marker for T790M status in tumor tissue. |
| Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Predose (within 90 minutes prior to start of infusion) and postdose (10 minutes after the end of infusion) on Days 1 and 57 | The CEOI of oleclumab is reported. |
| Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time | Predose (within 90 minutes prior to start of infusion) on Day 57 | The Ctrough of oleclumab is reported. |
| Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, and 4 hours) on Days 1 and 29 | The Cmax of osimertinib and AZ5104 are reported. |
| Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57 | The Cmax of AZD4635, SSP-005173X, and SSP-005174X are reported. |
| Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57 | The Tmax of AZD4635, SSP-005173X, and SSP-005174X are reported. |
| Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57 | The AUC0-24 of AZD4635, SSP-005173X, and SSP-005174X are reported. |
| Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies | Predose on Days 1 (Baseline), 29, and 57, and later every 12 weeks through the 12 months and 90 days after the last dose of study drug (approximately 37 months) | Number of participants with positive post-baseline for anti-oleclumab antibodies are reported. |
Countries
South Korea, Taiwan, United States
Contacts
STUDY_DIRECTORMedImmune LLC
MedImmune LLC
Participant flow
Pre-assignment details
The results data are reported per the primary completion date. There will be no updated results for all outcome measures at the time of end of study.
Participants by arm
| Arm | Count |
|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 In Part 1 (dose-escalation), participants received intravenous oleclumab (MEDI9447) Dose 1 every 2 weeks (Q2W) and oral osimertinib Dose 1 once daily (QD). | 5 |
| Oleclumab Dose 2 + Osimertinib Dose 1 In Part 1 (dose-escalation), participants received intravenous oleclumab Dose 2 Q2W and oral osimertinib Dose 1 QD. In Part 2 (dose-expansion), participants (including participants dosed at the RP2D in Part 1) received IV oleclumab Dose 2 Q2W and oral osimertinib Dose 1 QD until documentation of disease progression, intolerable toxicity, or development of other reason for treatment discontinuation, whichever occurred first. | 21 |
| Oleclumab Dose 1 + AZD4635 Dose 1 In Part 1 (dose-escalation), participants received intravenous oleclumab Dose 1 Q2W and oral AZD4635 Dose 1 QD. | 6 |
| Oleclumab Dose 1 + AZD4635 Dose 2 In Part 1 (dose-escalation), participants received intravenous oleclumab Dose 1 Q2W and oral AZD4635 Dose 2 QD. | 6 |
| Oleclumab Dose 2 + AZD4635 Dose 2 In Part 1 (dose-escalation), participants received intravenous oleclumab Dose 2 Q2W and oral AZD4635 Dose 2 QD. | 5 |
| Total | 43 |
Baseline characteristics
| Characteristic | Oleclumab Dose 1 + Osimertinib Dose 1 | Oleclumab Dose 2 + Osimertinib Dose 1 | Oleclumab Dose 1 + AZD4635 Dose 1 | Oleclumab Dose 1 + AZD4635 Dose 2 | Oleclumab Dose 2 + AZD4635 Dose 2 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.2 Years STANDARD_DEVIATION 2.9 | 61.4 Years STANDARD_DEVIATION 10.3 | 64.5 Years STANDARD_DEVIATION 10.3 | 65.2 Years STANDARD_DEVIATION 13.1 | 70.6 Years STANDARD_DEVIATION 8.8 | 63.4 Years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 21 Participants | 6 Participants | 6 Participants | 5 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 19 Participants | 0 Participants | 2 Participants | 1 Participants | 26 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 6 Participants | 4 Participants | 4 Participants | 17 Participants |
| Sex: Female, Male Female | 4 Participants | 10 Participants | 4 Participants | 5 Participants | 4 Participants | 27 Participants |
| Sex: Female, Male Male | 1 Participants | 11 Participants | 2 Participants | 1 Participants | 1 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 5 | 9 / 21 | 3 / 6 | 2 / 6 | 3 / 5 |
| other Total, other adverse events | 5 / 5 | 21 / 21 | 6 / 6 | 5 / 6 | 5 / 5 |
| serious Total, serious adverse events | 3 / 5 | 6 / 21 | 4 / 6 | 1 / 6 | 3 / 5 |
Outcome results
Primary
Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2
Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, and urinalysis.
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | White blood cell count decreased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypoalbuminaemia | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperglycaemia | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutrophil count decreased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood albumin decreased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypocalcaemia | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatinine increased | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Leukopenia | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypokalaemia | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Amylase increased | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypomagnesaemia | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Haemoglobin decreased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood alkaline phosphatase increased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypophosphataemia | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Aspartate aminotransferase increased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutropenia | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Anaemia | 2 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatine phosphokinase increased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Lipase increased | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Alanine aminotransferase increased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypothyroidism | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercholesterolaemia | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Platelet count decreased | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Thrombocytopenia | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperkalaemia | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyponatraemia | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercalcaemia | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatine phosphokinase increased | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Anaemia | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Alanine aminotransferase increased | 2 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Amylase increased | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Aspartate aminotransferase increased | 3 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Lipase increased | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercholesterolaemia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperkalaemia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypoalbuminaemia | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypocalcaemia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypokalaemia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypomagnesaemia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyponatraemia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypophosphataemia | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Leukopenia | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood albumin decreased | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutrophil count decreased | 2 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | White blood cell count decreased | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercalcaemia | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Thrombocytopenia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypothyroidism | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Platelet count decreased | 2 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutropenia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood alkaline phosphatase increased | 2 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatinine increased | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperglycaemia | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Haemoglobin decreased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Thrombocytopenia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood albumin decreased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutrophil count decreased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | White blood cell count decreased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperkalaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercholesterolaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Anaemia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Lipase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Haemoglobin decreased | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypothyroidism | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatine phosphokinase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Platelet count decreased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercalcaemia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutropenia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Aspartate aminotransferase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Amylase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood alkaline phosphatase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatinine increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperglycaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypoalbuminaemia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypocalcaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypokalaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypomagnesaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyponatraemia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Alanine aminotransferase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypophosphataemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Leukopenia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypokalaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Amylase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Platelet count decreased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercholesterolaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood albumin decreased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypocalcaemia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Haemoglobin decreased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Leukopenia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypoalbuminaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercalcaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypomagnesaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood alkaline phosphatase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperkalaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypophosphataemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Alanine aminotransferase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | White blood cell count decreased | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Anaemia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutropenia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatine phosphokinase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperglycaemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Aspartate aminotransferase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Thrombocytopenia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutrophil count decreased | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatinine increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Lipase increased | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyponatraemia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypothyroidism | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Lipase increased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatinine increased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Aspartate aminotransferase increased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Platelet count decreased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Anaemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypokalaemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | White blood cell count decreased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Amylase increased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypophosphataemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood alkaline phosphatase increased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Alanine aminotransferase increased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercalcaemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypomagnesaemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypothyroidism | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypoalbuminaemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyponatraemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood albumin decreased | 1 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Haemoglobin decreased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutropenia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypercholesterolaemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Neutrophil count decreased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Blood creatine phosphokinase increased | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hypocalcaemia | 1 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Leukopenia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Thrombocytopenia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperglycaemia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2 | Hyperkalaemia | 0 Participants |
Primary
Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2
Participants with abnormal vital signs (heart rate, blood pressure, temperature, and respiratory rate) and physical examination reported as TEAEs are reported.
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypertension | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypotension | 1 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Pyrexia | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypoxia | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypotension | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypertension | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypoxia | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Pyrexia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypoxia | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypotension | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Pyrexia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypertension | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypertension | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypotension | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Pyrexia | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypoxia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Pyrexia | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypoxia | 1 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypotension | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2 | Hypertension | 0 Participants |
Primary
Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1
A DLT was defined as \>= Grade 3 toxicity or adverse events (AE) occurred during DLT evaluation period which included any Grade 4 immune-mediated (immune nature) AE, anemia, thrombocytopenia (present \> 4 days), or neutropenia (present \> 4 days); \>= Grade 3 colitis or pneumonitis or interstitial lung disease (ILD); \>= Grade 3 nausea, vomiting, or diarrhea (not resolved to \<= Grade 2 in 3 days); Grade 2 pneumonitis or ILD (not resolved to \<= Grade 1 in 3 days); Grade 3 thrombocytopenia with bleeding, any grade febrile neutropenia; convulsions, seizures, or stroke; protocol defined elevations of isolated liver transaminase, isolated total bilirubin (TBL), or Hy's Law; confirmed QT interval corrected for heart rate by Fridericia's formula prolongation (\>= 501 msec) on triplicate electrocardiograms within a short period of time; or any other toxicity greater than that at baseline, was clinically significant and/or unacceptable, and was judged to be a DLT by the Dose Escalation Committee.
Time frame: From Day 1 to Day 28 after first dose of study drug
Population: The DLT-evaluable population included all participants who enrolled in the dose-escalation phase, received all planned doses of oleclumab and at least 75% of the daily administrations of osimertinib or AZD4635 during the DLT-evaluation period and completed the safety follow-up through the DLT-evaluation period or experienced any DLTs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1 | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1 | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1 | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1 | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1 | 0 Participants |
Primary
Number of Participants With Notable QTc Interval in Parts 1 and 2
Notable QTc intervals included single beat changes from baseline (Day 1) values (\> 30, \> 60, and \> 90 milliseconds). Participants who had notable QTc interval are reported.
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 60 milliseconds | 0 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 30 milliseconds | 2 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 90 milliseconds | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 90 milliseconds | 0 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 30 milliseconds | 6 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 60 milliseconds | 2 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 60 milliseconds | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 90 milliseconds | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 30 milliseconds | 2 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 60 milliseconds | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 30 milliseconds | 2 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 90 milliseconds | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 60 milliseconds | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 90 milliseconds | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Notable QTc Interval in Parts 1 and 2 | Single Beat change from baseline, Change > 30 milliseconds | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2
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: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TEAEs | 5 Participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TESAEs | 3 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TESAEs | 6 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TEAEs | 21 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TESAEs | 4 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TEAEs | 6 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TESAEs | 1 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TEAEs | 5 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TESAEs | 3 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2 | Any TEAEs | 5 Participants |
Primary
Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Part 2
The OR is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no 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: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Part 2 | 19 Percentage of participants |
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
The AUC0-24 of AZD4635, SSP-005173X, and SSP-005174X are reported.
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
Population: The PK population included all participants who received any study drug, analyzed according to the treatment they actually received, and had at least one quantifiable post-dose concentration with no important protocol deviations or AEs considered to impact the PK data. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 2546 h*ng/mL | Geometric Coefficient of Variation 27.24 |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 84.08 h*ng/mL | Geometric Coefficient of Variation 94.72 |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 304.4 h*ng/mL | Geometric Coefficient of Variation 54.74 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 57 | NA h*ng/mL | — |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 76.57 h*ng/mL | Geometric Coefficient of Variation 68.17 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 57 | NA h*ng/mL | — |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 231.9 h*ng/mL | Geometric Coefficient of Variation 65.94 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 57 | NA h*ng/mL | — |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 1324 h*ng/mL | Geometric Coefficient of Variation 28.02 |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 57 | NA h*ng/mL | — |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 57 | NA h*ng/mL | — |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 57 | NA h*ng/mL | — |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 192.4 h*ng/mL | Geometric Coefficient of Variation 24.54 |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 59.88 h*ng/mL | Geometric Coefficient of Variation 61.87 |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 1624 h*ng/mL | Geometric Coefficient of Variation 20.32 |
Secondary
Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
The Cmax of AZD4635, SSP-005173X, and SSP-005174X are reported.
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
Population: The PK population included all participants who received any study drug, analyzed according to the treatment they actually received, and had at least one quantifiable post-dose concentration with no important protocol deviations or AEs considered to impact the PK data. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 9.238 ng/mL | Geometric Coefficient of Variation 62.78 |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 67.78 ng/mL | Geometric Coefficient of Variation 30.28 |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 548.2 ng/mL | Geometric Coefficient of Variation 19.57 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 12.54 ng/mL | Geometric Coefficient of Variation 52.36 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 57 | NA ng/mL | — |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 330.6 ng/mL | Geometric Coefficient of Variation 34.02 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 57 | NA ng/mL | — |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 58.18 ng/mL | Geometric Coefficient of Variation 54.66 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 57 | NA ng/mL | — |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 57 | NA ng/mL | — |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 319.5 ng/mL | Geometric Coefficient of Variation 17.93 |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 57 | NA ng/mL | — |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 6.747 ng/mL | Geometric Coefficient of Variation 66.91 |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 57 | NA ng/mL | — |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 40.60 ng/mL | Geometric Coefficient of Variation 32.19 |
Secondary
Duration of Response (DoR) Per RECIST v 1.1 for Parts 1 and 2
The DoR is defined as duration from the first documentation of OR (confirmed CR or PR) to the first documented disease progression based on RECIST v1.1 guidelines or death due to any cause, whichever occurs first. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no 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. The progressive disease is defined at least a 20% increase in sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The DoR was analyzed using Kaplan-Meier method.
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received. The DoR was analyzed for participants who achieved OR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Duration of Response (DoR) Per RECIST v 1.1 for Parts 1 and 2 | 11.4 Months |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Duration of Response (DoR) Per RECIST v 1.1 for Parts 1 and 2 | NA Months |
Secondary
Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104)
The Cmax of osimertinib and AZ5104 are reported.
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, and 4 hours) on Days 1 and 29
Population: The PK population included all participants who received any study drug, analyzed according to the treatment they actually received, and had at least one quantifiable post-dose concentration with no important protocol deviations or AEs considered to impact the PK data. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | Osimertinib, Day 1 | 151.9 nM | Geometric Coefficient of Variation 18.73 |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | AZ5104, Day 1 | 3.271 nM | Geometric Coefficient of Variation 60.73 |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | Osimertinib, Day 29 | 529.9 nM | Geometric Coefficient of Variation 28.46 |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | AZ5104, Day 29 | 52.06 nM | Geometric Coefficient of Variation 43.62 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | Osimertinib, Day 29 | 484.9 nM | Geometric Coefficient of Variation 48.69 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | Osimertinib, Day 1 | 130.5 nM | Geometric Coefficient of Variation 92.63 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | AZ5104, Day 29 | 45.30 nM | Geometric Coefficient of Variation 53.84 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104) | AZ5104, Day 1 | 3.954 nM | Geometric Coefficient of Variation 72.97 |
Secondary
Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies
Number of participants with positive post-baseline for anti-oleclumab antibodies are reported.
Time frame: Predose on Days 1 (Baseline), 29, and 57, and later every 12 weeks through the 12 months and 90 days after the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies | 1 Participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies | 0 Participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies | 0 Participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies | 0 Participants |
Secondary
Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time
The Ctrough of oleclumab is reported.
Time frame: Predose (within 90 minutes prior to start of infusion) on Day 57
Population: The PK population included all participants who received any study drug, analyzed according to the treatment they actually received, and had at least one quantifiable post-dose concentration with no important protocol deviations or AEs considered to impact the PK data. ''Number of participants analyzed' denotes the number of participants who had adequate PK sample and were evaluated for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time | 271.5 µg/mL | Geometric Coefficient of Variation 38.03 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time | 315.5 µg/mL | Geometric Coefficient of Variation 35.42 |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time | NA µg/mL | — |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time | NA µg/mL | — |
Secondary
Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time
The CEOI of oleclumab is reported.
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (10 minutes after the end of infusion) on Days 1 and 57
Population: Pharmacokinetic (PK) population included all participants who received any study drug, analyzed according to the treatment they actually received, and had at least one quantifiable post-dose concentration with no important protocol deviations or AEs considered to impact the PK data. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 57 | 926.4 µg/mL | Geometric Coefficient of Variation 15.55 |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 1 | 545.7 µg/mL | Geometric Coefficient of Variation 22.29 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 1 | 787.6 µg/mL | Geometric Coefficient of Variation 31.27 |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 57 | 1183 µg/mL | Geometric Coefficient of Variation 24.76 |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 1 | 494.6 µg/mL | Geometric Coefficient of Variation 23.69 |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 57 | NA µg/mL | — |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 1 | 385.4 µg/mL | Geometric Coefficient of Variation 23.51 |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 57 | NA µg/mL | — |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time | Day 1 | 633.3 µg/mL | Geometric Coefficient of Variation 33.45 |
Secondary
Overall Survival (OS) for Parts 1 and 2
The OS is defined as the time from the start of study treatment until death due to any cause. Participants who are alive at the time of data cut-off had OS censored at the last known to be alive date. The OS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Overall Survival (OS) for Parts 1 and 2 | 21.9 Months |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Overall Survival (OS) for Parts 1 and 2 | 24.8 Months |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Overall Survival (OS) for Parts 1 and 2 | 16.4 Months |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Overall Survival (OS) for Parts 1 and 2 | 27.4 Months |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Overall Survival (OS) for Parts 1 and 2 | 7.1 Months |
Secondary
Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2
The T790M status was determined by plasma testing in a central laboratory at Baseline (Days -28 to -1). The DC is defined as percentage of participants with CR, PR, or SD (maintained by \>= 8 week) based on RECIST v1.1 guidelines. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as \>= 30% decrease in the sum of longest diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no non-target lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum longest diameter since the study treatment started, and persistence of one or more non-target lesion(s). Cell-free circulating tumor deoxyribonucleic acid (ctDNA) from liquid biopsy was used as a surrogate marker for T790M status in tumor tissue.
Time frame: From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received. 'Number of participants analyzed' denotes participants who had T790M status positive or negative at baseline (Days -28 to -1).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | DC by T790M status positive | 100 Percentage of participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | DC by T790M status negative | 75.0 Percentage of participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | DC by T790M status positive | 100 Percentage of participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | DC by T790M status negative | 82.4 Percentage of participants |
Secondary
Percentage of Participants With Disease Control (DC) in Parts 1 and 2
The DC is defined as percentage of participants with CR, PR, or stable disease (SD, which was maintained by \>= 8 week) based on RECIST v1.1 guidelines. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no non-target lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum longest diameter since the study treatment started, and non-progressive disease and not evaluable or no non-target lesion.
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Percentage of Participants With Disease Control (DC) in Parts 1 and 2 | 80.0 Percentage of participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Percentage of Participants With Disease Control (DC) in Parts 1 and 2 | 81.0 Percentage of participants |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Percentage of Participants With Disease Control (DC) in Parts 1 and 2 | 0 Percentage of participants |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Percentage of Participants With Disease Control (DC) in Parts 1 and 2 | 16.7 Percentage of participants |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Percentage of Participants With Disease Control (DC) in Parts 1 and 2 | 0 Percentage of participants |
Secondary
Percentage of Participants With OR by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2
The T790M status was determined by plasma testing in a central laboratory at Baseline (Days -28 to -1). The OR is defined as confirmed CR or confirmed PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no 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. Cell-free circulating tumor deoxyribonucleic acid (ctDNA) from liquid biopsy was used as a surrogate marker for T790M status in tumor tissue.
Time frame: From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received. 'Number of participants analyzed' denotes participants who had T790M status positive or negative at baseline (Days -28 to -1). The T790M status results was assessed only for participants in 'Oleclumab + Osimertinib' arms.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Percentage of Participants With OR by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | OR by T790M status positive | 100 Percentage of participants |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Percentage of Participants With OR by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | OR by T790M status negative | 25.0 Percentage of participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Percentage of Participants With OR by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | OR by T790M status positive | 66.7 Percentage of participants |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Percentage of Participants With OR by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2 | OR by T790M status negative | 11.8 Percentage of participants |
Secondary
Progression Free Survival (PFS) for Parts 1 and 2
The PFS is defined as the time from the start of study treatment until the documentation of disease progression based on RECIST version 1.1 or death due to any cause, whichever occurs first, regardless of whether the participant received subsequent anticancer treatment prior to progression. 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. Participants who were alive and progression-free at the time of data cut-off for analysis had PFS censored at the last tumor assessment date. The PFS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Progression Free Survival (PFS) for Parts 1 and 2 | 6.5 Months |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Progression Free Survival (PFS) for Parts 1 and 2 | 11.0 Months |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Progression Free Survival (PFS) for Parts 1 and 2 | 1.4 Months |
| Oleclumab Dose 1 + AZD4635 Dose 2 | Progression Free Survival (PFS) for Parts 1 and 2 | 1.8 Months |
| Oleclumab Dose 2 + AZD4635 Dose 2 | Progression Free Survival (PFS) for Parts 1 and 2 | 1.9 Months |
Secondary
Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
The Tmax of AZD4635, SSP-005173X, and SSP-005174X are reported.
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
Population: The PK population included all participants who received any study drug, analyzed according to the treatment they actually received, and had at least one quantifiable post-dose concentration with no important protocol deviations or AEs considered to impact the PK data. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure. 'Number analyzed' denotes the number of participants evaluated for the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oleclumab Dose 1 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 1.54 Hour |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 1.03 Hour |
| Oleclumab Dose 1 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 1.03 Hour |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 1.07 Hour |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 1.07 Hour |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 57 | NA Hour |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 57 | NA Hour |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 1.93 Hour |
| Oleclumab Dose 2 + Osimertinib Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 57 | NA Hour |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 57 | NA Hour |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 1 | 1.05 Hour |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 1 | 1.05 Hour |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005174X, Day 57 | NA Hour |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | AZD4635, Day 57 | NA Hour |
| Oleclumab Dose 1 + AZD4635 Dose 1 | Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X) | SSP-005173X, Day 1 | 1.22 Hour |