Trial Outcomes & Findings for AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Blood Cancer (NCT NCT04630756)

NCT ID: NCT04630756

Last Updated: 2025-04-09

Results Overview

Safety and tolerability of AZD4573 in combination with acalabrutinib was assessed.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
• Results posted on: 2025-04-09

Participant Flow

This study was conducted from 17 February 2021 to 08 September 2023. Module 1 was conducted at 17 study centers in 10 countries. Module 2 was conducted at 2 sites in the United States.

The screening period was of 30 days for both parts of the study. Informed Consent Form (ICF) was signed prior to screening procedures. All the study assessments were performed as per the schedule of assessment. Participants who met the eligibility criteria were randomized to study intervention in addition to receiving background local standard of care therapy.

Participant milestones

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.	Module 2 Period 1 + 2: AZD4573 12 mg Monotherapy + Combination BID Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.
Module 1 Part A: AZD4573 9 mg STARTED	9	0	0
Module 1 Part A: AZD4573 9 mg COMPLETED	8	0	0
Module 1 Part A: AZD4573 9 mg NOT COMPLETED	1	0	0
Module 1 Part B: AZD4573 12 mg STARTED	0	28	0
Module 1 Part B: AZD4573 12 mg COMPLETED	0	28	0
Module 1 Part B: AZD4573 12 mg NOT COMPLETED	0	0	0
Module 2 Period 1: AZD4573 Monotherapy STARTED	0	0	3
Module 2 Period 1: AZD4573 Monotherapy COMPLETED	0	0	3
Module 2 Period 1: AZD4573 Monotherapy NOT COMPLETED	0	0	0
Module 2 Period 2: AZD4573 Combination STARTED	0	0	3
Module 2 Period 2: AZD4573 Combination COMPLETED	0	0	3
Module 2 Period 2: AZD4573 Combination NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.	Module 2 Period 1 + 2: AZD4573 12 mg Monotherapy + Combination BID Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.
Module 1 Part A: AZD4573 9 mg Ongoing subjects in Post Trial Access Program	1	0	0

Baseline Characteristics

AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Blood Cancer

Baseline characteristics by cohort

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.	Module 2 Period 1 + 2: AZD4573 12 mg Monotherapy + Combination BID n=3 Participants Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	17 Participants n=7 Participants	3 Participants n=5 Participants	27 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	11 Participants n=7 Participants	0 Participants n=5 Participants	13 Participants n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	10 Participants n=7 Participants	0 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	18 Participants n=7 Participants	3 Participants n=5 Participants	26 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	8 Participants n=7 Participants	0 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	17 Participants n=7 Participants	2 Participants n=5 Participants	25 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

Population: The safety analysis set included all participants who received any amount of AZD4573 and/or acalabrutinib.

Safety and tolerability of AZD4573 in combination with acalabrutinib was assessed.

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Number of Participants With Adverse Events Any adverse event (AE)	9 Participants	28 Participants
Module 1: Number of Participants With Adverse Events Any serious adverse event (SAE)	4 Participants	16 Participants

PRIMARY outcome

Timeframe: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

Population: The safety analysis set included all participants who received any amount of AZD4573 and/or acalabrutinib.

Assessed safety and confirmed the RP2D of AZD4573 monotherapy in MCL participants and assessed the safety and tolerability of AZD4573 in combination with acalabrutinib in participants administered AZD4573 monotherapy.

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=3 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 2: Number of Participants With Adverse Events Any AE	3 Participants	—
Module 2: Number of Participants With Adverse Events Any SAE	1 Participants	—

PRIMARY outcome

Timeframe: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

Population: The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment.

Overall response rate (ORR), defined as the proportion of participants who have a tumour response (complete response [CR] and partial response [PR]).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Overall Response Rate (ORR) of AZD4573 in Combination With Acalabrutinib	44.4 Percentage of participants with response Interval 13.7 to 78.8	50.0 Percentage of participants with response Interval 30.6 to 69.4

SECONDARY outcome

Timeframe: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

Population: The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment.

CR is defined as no detectable evidence of tumor, according to the revised response criteria for malignant lymphoma.

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Complete Response (CR) Rate	11.1 Percentage of participants with response Interval 0.3 to 48.2	21.4 Percentage of participants with response Interval 8.3 to 41.0

SECONDARY outcome

Timeframe: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

Population: The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment.

DoR, defined as the time from the first objective response of CR or PR to the time of documented disease progression or death due to any cause, whichever occurs first.

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Duration of Response (DoR)	4.4 Months Interval 4.1 to Values are not calculated due to insufficient number of participants with events.	3.3 Months Interval 1.2 to 6.2

SECONDARY outcome

Timeframe: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

Population: The full analysis set included all participants who received any amount of study intervention.

PFS, defined as the time from first dose date to documented disease progression, or death from any cause, whichever occurs first

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Progression Free Survival (PFS)	2.1 Months Interval 0.3 to 6.44	2.8 Months Interval 1.91 to 3.98

SECONDARY outcome

Timeframe: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

Population: The full analysis set included all participants who received any amount of study intervention.

OS, defined as the time from first dose until the date of death from any cause.

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Overall Survival (OS)	NA Months Interval 3.52 to Values are not calculated due to insufficient number of participants with events.	8.8 Months Interval 3.91 to Values are not calculated due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=12 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Cmax of AZD4573 Cycle 1 Week 1 Day 1	164.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 469.0	112.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 70.20
Module 1: Cmax of AZD4573 Cycle 1 Week 2 Day 1	235.7 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 359.3	185.3 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 50.61
Module 1: Cmax of AZD4573 Cycle 1 Week 3 Day 1	337.8 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 194.3	270.8 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 38.61
Module 1: Cmax of AZD4573 Cycle 2 Week 1 Day 1	643.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 578.0	294.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 48.83

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=7 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=11 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Cmax of Acalabrutinib Cycle 1 Week 1 Day 1	219.9 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 66.94	306.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 76.06
Module 1: Cmax of Acalabrutinib Cycle 1 Week 2 Day 1	209.8 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 45.79	322.7 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 95.53
Module 1: Cmax of Acalabrutinib Cycle 1 Week 3 Day 1	232.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 74.77	274.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 78.98
Module 1: Cmax of Acalabrutinib Cycle 2 Week 1 Day 1	217.5 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 100.8	256.7 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 67.75

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=7 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=11 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Cmax of ACP-5862 Cycle 1 Week 1 Day 1	199.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 129.3	250.2 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 78.12
Module 1: Cmax of ACP-5862 Cycle 1 Week 2 Day 1	382.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 51.58	288.0 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 63.26
Module 1: Cmax of ACP-5862 Cycle 1 Week 3 Day 1	320.8 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 35.92	282.9 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 55.76
Module 1: Cmax of ACP-5862 Cycle 2 Week 1 Day 1	304.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 79.28	251.8 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 45.54

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=8 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=12 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: AUClast of AZD4573 Cycle 1 Week 1 Day 1	532.9 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 164.5	561.3 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 60.83
Module 1: AUClast of AZD4573 Cycle 1 Week 2 Day 1	845.3 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 134.8	929.0 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 55.85
Module 1: AUClast of AZD4573 Cycle 1 Week 3 Day 1	1273 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 127.7	1697 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 62.55
Module 1: AUClast of AZD4573 Cycle 2 Week 1 Day 1	1939 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 330.9	1439 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 90.63

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=7 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=11 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: AUClast of Acalabrutinib Cycle 1 Week 1 Day 1	493.9 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 58.91	631.4 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 69.98
Module 1: AUClast of Acalabrutinib Cycle 1 Week 2 Day 1	520.9 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 46.04	638.2 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 81.66
Module 1: AUClast of Acalabrutinib Cycle 1 Week 3 Day 1	475.9 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 45.57	570.7 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 67.75
Module 1: AUClast of Acalabrutinib Cycle 2 Week 1 Day 1	481.8 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 58.39	424.5 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 162.8

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=7 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=11 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: AUClast of ACP-5862 Cycle 1 Week 1 Day 1	673.9 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 93.89	870.8 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 68.73
Module 1: AUClast of ACP-5862 Cycle 1 Week 2 Day 1	1173 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 48.03	1135 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 54.95
Module 1: AUClast of ACP-5862 Cycle 1 Week 3 Day 1	1204 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 36.24	1093 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 54.50
Module 1: AUClast of ACP-5862 Cycle 2 Week 1 Day 1	941.9 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 102.5	849.3 hours*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 60.56

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=5 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=9 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: AUCinf of AZD4573 Cycle 1 Week 1 Day 1	NA h*ng/mL Geometric Coefficient of Variation NA Geometric Mean (Geometric Coefficient of Variation) is not calculable for a single participant.	640.5 h*ng/mL Geometric Coefficient of Variation 15.33
Module 1: AUCinf of AZD4573 Cycle 1 Week 2 Day 1	1188 h*ng/mL Geometric Coefficient of Variation 160.1	847.4 h*ng/mL Geometric Coefficient of Variation 68.22
Module 1: AUCinf of AZD4573 Cycle 1 Week 3 Day 1	1588 h*ng/mL Geometric Coefficient of Variation 169.6	1736 h*ng/mL Geometric Coefficient of Variation 67.09
Module 1: AUCinf of AZD4573 Cycle 2 Week 1 Day 1	4672 h*ng/mL Geometric Coefficient of Variation 162.9	1853 h*ng/mL Geometric Coefficient of Variation 29.55

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=3 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=5 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: AUCinf of Acalabrutinib Cycle 1 Week 1 Day 1	600.1 h*ng/mL Geometric Coefficient of Variation 34.99	501.3 h*ng/mL Geometric Coefficient of Variation 58.03

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=2 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=4 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: AUCinf of ACP-5862 Cycle 1 Week 1 Day 1	NA h*ng/mL Geometric Coefficient of Variation NA Geometric Mean (Geometric Coefficient of Variation) values is not calculated for less than three participants.	935.2 h*ng/mL Geometric Coefficient of Variation 38.81

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Time to reach peak or maximum observed concentration following drug administration (tmax).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=8 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=12 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Tmax of AZD4573 Cycle 1 Week 1 Day 1	1.992 Hours (h) Interval 0.75 to 4.17	2.083 Hours (h) Interval 1.0 to 10.5
Module 1: Tmax of AZD4573 Cycle 1 Week 2 Day 1	1.892 Hours (h) Interval 1.0 to 3.0	2.033 Hours (h) Interval 1.05 to 2.15
Module 1: Tmax of AZD4573 Cycle 1 Week 3 Day 1	2.192 Hours (h) Interval 0.933 to 3.32	2.000 Hours (h) Interval 1.03 to 2.15
Module 1: Tmax of AZD4573 Cycle 2 Week 1 Day 1	2.067 Hours (h) Interval 1.0 to 2.22	2.083 Hours (h) Interval 1.85 to 3.63

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Time to reach peak or maximum observed concentration following drug administration (tmax).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=7 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=11 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Tmax of Acalabrutinib Cycle 1 Week 1 Day 1	1.242 Hours (h) Interval 1.02 to 3.8	1.117 Hours (h) Interval 0.933 to 2.65
Module 1: Tmax of Acalabrutinib Cycle 1 Week 2 Day 1	2.017 Hours (h) Interval 1.0 to 4.52	1.133 Hours (h) Interval 0.95 to 11.6
Module 1: Tmax of Acalabrutinib Cycle 1 Week 3 Day 1	1.233 Hours (h) Interval 1.0 to 3.17	1.433 Hours (h) Interval 0.85 to 4.0
Module 1: Tmax of Acalabrutinib Cycle 2 Week 1 Day 1	1.933 Hours (h) Interval 1.03 to 5.75	1.200 Hours (h) Interval 0.833 to 2.25

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Time to reach peak or maximum observed concentration following drug administration (tmax).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=7 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=11 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: Tmax of ACP-5862 Cycle 1 Week 1 Day 1	3.067 Hours (h) Interval 1.02 to 7.0	1.117 Hours (h) Interval 0.933 to 7.08
Module 1: Tmax of ACP-5862 Cycle 1 Week 2 Day 1	2.075 Hours (h) Interval 1.08 to 7.52	2.117 Hours (h) Interval 1.05 to 11.6
Module 1: Tmax of ACP-5862 Cycle 1 Week 3 Day 1	1.233 Hours (h) Interval 1.0 to 4.58	1.892 Hours (h) Interval 0.85 to 4.0
Module 1: Tmax of ACP-5862 Cycle 2 Week 1 Day 1	2.167 Hours (h) Interval 2.05 to 8.92	2.117 Hours (h) Interval 0.917 to 4.13

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=5 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=10 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: t1/2 of AZD4573 Cycle 1 Week 1 Day 1	NA Hours (h) Geometric Coefficient of Variation NA Geometric Mean (Geometric Coefficient of Variation) is not calculable for a single participant.	3.692 Hours (h) Geometric Coefficient of Variation 37.98
Module 1: t1/2 of AZD4573 Cycle 1 Week 2 Day 1	3.364 Hours (h) Geometric Coefficient of Variation 43.80	5.407 Hours (h) Geometric Coefficient of Variation 73.47
Module 1: t1/2 of AZD4573 Cycle 1 Week 3 Day 1	4.465 Hours (h) Geometric Coefficient of Variation 42.28	6.177 Hours (h) Geometric Coefficient of Variation 30.16
Module 1: t1/2 of AZD4573 Cycle 2 Week 1 Day 1	6.508 Hours (h) Geometric Coefficient of Variation 30.61	5.808 Hours (h) Geometric Coefficient of Variation 25.52

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=6 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=6 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: t1/2 of Acalabrutinib Cycle 1 Week 1 Day 1	1.332 Hours (h) Geometric Coefficient of Variation 22.01	1.108 Hours (h) Geometric Coefficient of Variation 12.06
Module 1: t1/2 of Acalabrutinib Cycle 1 Week 2 Day 1	1.383 Hours (h) Geometric Coefficient of Variation 49.15	1.274 Hours (h) Geometric Coefficient of Variation 25.09
Module 1: t1/2 of Acalabrutinib Cycle 1 Week 3 Day 1	1.238 Hours (h) Geometric Coefficient of Variation 20.93	1.546 Hours (h) Geometric Coefficient of Variation 38.08
Module 1: t1/2 of Acalabrutinib Cycle 2 Week 1 Day 1	NA Hours (h) Geometric Coefficient of Variation NA Geometric Mean (Geometric Coefficient of Variation) values was not calculated for less than three participants.	1.398 Hours (h) Geometric Coefficient of Variation 32.20

SECONDARY outcome

Timeframe: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1

Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.

Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2).

Outcome measures

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=5 Participants Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=6 Participants Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
Module 1: t1/2 of ACP-5862 Cycle 1 Week 1 Day 1	NA Hours (h) Geometric Coefficient of Variation NA Geometric Mean (Geometric Coefficient of Variation) is not calculated due to insufficient number of participants.	2.568 Hours (h) Geometric Coefficient of Variation 33.27
Module 1: t1/2 of ACP-5862 Cycle 1 Week 2 Day 1	NA Hours (h) Geometric Coefficient of Variation NA Geometric Mean (Geometric Coefficient of Variation) values is not calculated for less than three participants.	3.021 Hours (h) Geometric Coefficient of Variation 47.65
Module 1: t1/2 of ACP-5862 Cycle 1 Week 3 Day 1	2.650 Hours (h) Geometric Coefficient of Variation 34.68	3.557 Hours (h) Geometric Coefficient of Variation 38.06
Module 1: t1/2 of ACP-5862 Cycle 2 Week 1 Day 1	—	NA Hours (h) Geometric Coefficient of Variation NA Geometric Mean (Geometric Coefficient of Variation) values is not calculated for less than three participants.

Adverse Events

Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID

Serious events: 4 serious events

Other events: 9 other events

Deaths: 4 deaths

Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID

Serious events: 16 serious events

Other events: 28 other events

Deaths: 16 deaths

Module 2 Period 1 + 2: AZD4573 12 mg Monotherapy + Combination BID

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 participants at risk Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 participants at risk Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.	Module 2 Period 1 + 2: AZD4573 12 mg Monotherapy + Combination BID n=3 participants at risk Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.
Infections and infestations COVID-19	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Cellulitis	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Device related infection	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Pneumonia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	14.3% 4/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Urosepsis	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Blood and lymphatic system disorders Anaemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Immune system disorders Hypogammaglobulinaemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Nervous system disorders Presyncope	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Nervous system disorders Seizure	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Nervous system disorders Syncope	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Vomiting	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Pyrexia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Alanine aminotransferase increased	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Aspartate aminotransferase increased	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Blood bilirubin increased	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Blood creatinine increased	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Hepatic enzyme increased	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Liver function test abnormal	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Hepatitis B reactivation	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

Other adverse events

Measure	Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID n=9 participants at risk Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.	Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID n=28 participants at risk Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.	Module 2 Period 1 + 2: AZD4573 12 mg Monotherapy + Combination BID n=3 participants at risk Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	22.2% 2/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Abdominal discomfort	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Tumour lysis syndrome	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	21.4% 6/28 • Number of events 13 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Psychiatric disorders Insomnia	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Nervous system disorders Dizziness	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	17.9% 5/28 • Number of events 7 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Nervous system disorders Dizziness postural	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	28.6% 8/28 • Number of events 9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	66.7% 2/3 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Nervous system disorders Headache	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	21.4% 6/28 • Number of events 8 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Nervous system disorders Peripheral sensory neuropathy	11.1% 1/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Nervous system disorders Presyncope	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Eye disorders Punctate keratitis	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Eye disorders Scintillating scotoma	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hyponatraemia	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Ear and labyrinth disorders Deafness	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hypertriglyceridaemia	11.1% 1/9 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	14.3% 4/28 • Number of events 7 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	28.6% 8/28 • Number of events 14 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Cardiac disorders Atrial fibrillation	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Cardiac disorders Tachycardia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Vascular disorders Deep vein thrombosis	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Vascular disorders Hypotension	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	14.3% 4/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Vascular disorders Orthostatic hypotension	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Cough	11.1% 1/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	14.3% 4/28 • Number of events 6 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	17.9% 5/28 • Number of events 5 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	66.7% 2/3 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	25.0% 7/28 • Number of events 14 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Hiccups	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations COVID-19	33.3% 3/9 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Catheter site infection	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Cellulitis	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Escherichia urinary tract infection	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Fungal skin infection	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Nasopharyngitis	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Oral candidiasis	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Oral herpes	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Pharyngitis	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Pneumonia	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Respiratory syncytial virus infection	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Rhinovirus infection	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip neoplasm benign	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Blood and lymphatic system disorders Anaemia	33.3% 3/9 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	50.0% 14/28 • Number of events 23 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Blood and lymphatic system disorders Leukopenia	33.3% 3/9 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Blood and lymphatic system disorders Lymphopenia	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Blood and lymphatic system disorders Neutropenia	100.0% 9/9 • Number of events 86 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	89.3% 25/28 • Number of events 126 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	100.0% 3/3 • Number of events 6 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Blood and lymphatic system disorders Thrombocytopenia	66.7% 6/9 • Number of events 11 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	57.1% 16/28 • Number of events 46 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Decreased appetite	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	14.3% 4/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Dehydration	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Metabolism and nutrition disorders Hyperkalaemia	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Abdominal distension	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Abdominal pain	22.2% 2/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	66.7% 2/3 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Abdominal pain upper	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Constipation	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	14.3% 4/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	66.7% 2/3 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Diarrhoea	33.3% 3/9 • Number of events 7 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	50.0% 14/28 • Number of events 32 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	100.0% 3/3 • Number of events 5 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Dyspepsia	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Dysphagia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Epigastric discomfort	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	14.3% 4/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Nausea	44.4% 4/9 • Number of events 7 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	67.9% 19/28 • Number of events 33 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	66.7% 2/3 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Saliva altered	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Vomiting	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	39.3% 11/28 • Number of events 19 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Skin and subcutaneous tissue disorders Keratosis pilaris	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 4 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Skin and subcutaneous tissue disorders Rash macular	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Skin and subcutaneous tissue disorders Rash maculo-papular	22.2% 2/9 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 1/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Musculoskeletal and connective tissue disorders Back pain	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	17.9% 5/28 • Number of events 5 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Musculoskeletal and connective tissue disorders Myalgia	22.2% 2/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Renal and urinary disorders Glycosuria	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Renal and urinary disorders Proteinuria	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Application site erosion	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Asthenia	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Catheter site erythema	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Catheter site related reaction	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Device related thrombosis	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Fatigue	22.2% 2/9 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	39.3% 11/28 • Number of events 12 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	66.7% 2/3 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Injection site erythema	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Oedema peripheral	33.3% 3/9 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Peripheral swelling	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Pyrexia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	21.4% 6/28 • Number of events 6 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	66.7% 2/3 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Alanine aminotransferase increased	33.3% 3/9 • Number of events 6 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	53.6% 15/28 • Number of events 46 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Amylase increased	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	7.1% 2/28 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Aspartate aminotransferase increased	33.3% 3/9 • Number of events 12 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	53.6% 15/28 • Number of events 55 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Blood alkaline phosphatase increased	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Blood bilirubin increased	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 5 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Blood creatinine increased	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	14.3% 4/28 • Number of events 5 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Fibrin D dimer increased	11.1% 1/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Gamma-glutamyltransferase increased	22.2% 2/9 • Number of events 3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	10.7% 3/28 • Number of events 6 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Glutamate dehydrogenase increased	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Hepatic enzyme increased	11.1% 1/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Lipase increased	11.1% 1/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Transaminases increased	11.1% 1/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	3.6% 1/28 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations Weight increased	11.1% 1/9 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Injury, poisoning and procedural complications Contusion	11.1% 1/9 • Number of events 2 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	17.9% 5/28 • Number of events 6 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/3 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Infections and infestations Diverticulitis	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Abdominal pain lower	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Gastrointestinal disorders Dry mouth	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
General disorders Chest discomfort	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Investigations White blood cell count decreased	0.00% 0/9 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	0.00% 0/28 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)	33.3% 1/3 • Number of events 1 • From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)

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Restriction type: OTHER