Trial Outcomes & Findings for PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer (NCT NCT04099888)

NCT ID: NCT04099888

Last Updated: 2023-09-11

Results Overview

From date of randomisation to date of objective disease progression or death, whichever comes first (in months)

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 41 participants
• Primary outcome timeframe: Up to 18 months
• Results posted on: 2023-09-11

Participant Flow

Of the 41 enrolled participants, all met inclusion criteria and were randomized and included in the intent-to-great (ITT) analysis set.

Participant milestones

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Overall Study STARTED	21	20
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	21	20

Reasons for withdrawal

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Overall Study Study terminated by sponsor	9	11
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	5	6
Overall Study Death	5	2
Overall Study Other	1	0

Baseline Characteristics

PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer

Baseline characteristics by cohort

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=21 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy. Length of cycle is 3 weeks with PCI treatment at Day 1. Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=20 Participants Arm B: Gemcitabine/cisplatin chemotherapy. Length of cycle is 3 weeks. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Total n=41 Participants Total of all reporting groups
Age, Continuous	68.1 years STANDARD_DEVIATION 7.30 • n=5 Participants	64.4 years STANDARD_DEVIATION 11.43 • n=7 Participants	66.3 years STANDARD_DEVIATION 9.61 • n=5 Participants
Age, Customized <50 years of age	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Age, Customized 50 to <65 years of age	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Age, Customized >=65 years of age	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 18 months

Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).

From date of randomisation to date of objective disease progression or death, whichever comes first (in months)

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=19 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=15 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Progression-free Survival (PFS)	7.29 Months Interval 6.0 to 12.0	8.08 Months Interval 6.0 to 12.0

SECONDARY outcome

Timeframe: Up to 24 months

Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).

From date of randomisation to date of death from any cause (in months)

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=19 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=15 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Overall Survival (OS)	12 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to 18 months

Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).

Best response recorded from start of treatment until disease progression/recurrence (according to RECIST 1.1)

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=19 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=15 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Best Overall Response (BOR) Complete response	0 Participants	0 Participants
Best Overall Response (BOR) Partial response	3 Participants	3 Participants
Best Overall Response (BOR) Stable disease	12 Participants	11 Participants
Best Overall Response (BOR) Progressive disease	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 18 months

Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).

Proportion of patients with measurable disease at baseline who have at least one visit response with a complete response (CR) or partial response (PR) noted (according to RECIST 1.1)

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=19 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=15 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Objective Response Rate (ORR)	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 24 months

From first documented tumour response until first documented disease progression, or death in the absence of disease progression (in months)

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=3 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=3 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Duration of Response (DoR) Patient A	169 Days	NA Days Patient enrolled in Arm A: PCI treatment in conjunction with Standard of Care (SoC)
Duration of Response (DoR) Patient B	260 Days	NA Days Patient enrolled in Arm A: PCI treatment in conjunction with Standard of Care (SoC)
Duration of Response (DoR) Patient C	264 Days	NA Days Patient enrolled in Arm A: PCI treatment in conjunction with Standard of Care (SoC)
Duration of Response (DoR) Patient D	NA Days Patient enrolled in Arm B: Standard of Care (SoC)	85 Days
Duration of Response (DoR) Patient E	NA Days Patient enrolled in Arm B: Standard of Care (SoC)	1 Days
Duration of Response (DoR) Patient F	NA Days Patient enrolled in Arm B: Standard of Care (SoC)	1 Days

SECONDARY outcome

Timeframe: 6 months and 12 months

Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).

Proportion of patients with BOR of CR, PR or stable disease (SD) (according to RECIST 1.1) at or after the first follow-up scan, partial response or complete response

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=19 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=15 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Overall Disease Control Rate (DCR) Overall Disease Control Rate	15 Participants	14 Participants
Overall Disease Control Rate (DCR) Disease Control Rate at 6 Months	11 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to 18 months

Population: Only patients with measurable disease at baseline are included in this summary.

Best overall percentage change in tumour size from baseline

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=17 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=11 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Change in Tumor Size	-12.06 Percentage Change in Tumor Size Standard Deviation 28.008	-14.73 Percentage Change in Tumor Size Standard Deviation 16.377

SECONDARY outcome

Timeframe: Up to 12 months

Frequency and severity of loco-regional tumour related events and biliary complications

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=18 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=16 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Loco-regional Tumour-related Events and Biliary Complications	12 Participants	8 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Number and proportion of patients with AEs/SAEs

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=18 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=16 Participants Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Adverse Events (AEs)/Serious Adverse Events (SAEs)	12 Participants	8 Participants

SECONDARY outcome

Timeframe: Time Frame AUC calculated from time zero to C5-D8 (3 months from the first PCI treatment)

Population: AUC was calculated for each single patient and not for the population since the study was terminated and the amount of data was limited. No mean and standard deviation was calculated for the population

A non-compartmental analysis (NCA) was applied on the data. AUC from time zero to the last measured concentration (AUC 0-t) was initially estimated by the linear trapezoidal method.

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=13 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 101-01 1st dose	1017672 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 101-01 2nd dose	1399905 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 101-02	385730 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 101-03 1st dose	576835 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 101-03 2nd dose	600546 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 106-01 1st dose (No samples taken before 90 hrs, therefore AUC values is likely underestimated)	677373 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 106-01 2nd dose	874614 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 111-02 1st dose	492274 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 111-02 2nd dose	NA (ng/ml)*hrs One data point was measured post injection and AUC could not be calculated.	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 181-06 1st dose	566460 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 181-06 2nd dose	NA (ng/ml)*hrs Three data points was measured post injection. Two samples were measured in the distribution phase (30 min, 4 hours) , and only one sample was measured in the elimination phase (96 hours), AUC could therefore not be calculated.	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 183-03 1st dose	751771 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 183-03 2nd dose	475001 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 183-03 3rd dose	646845 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 187-02 1st dose	709053 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 187-02 2nd dose	383882 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 192-01	805049 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 303-01 1st dose	434347 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 303-01 2nd dose	NA (ng/ml)*hrs The interval between the two first measured samples post injection was too long to calculate AUC. No samples were measured between 30 min and approximately 7 weeks.	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 303-02 1st dose	681663 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 303-02 2nd dose	730864 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 401-01	521326 (ng/ml)*hrs	—
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. 501-01	549955 (ng/ml)*hrs	—

SECONDARY outcome

Timeframe: Timepoints for pharmacokinetic (PK) sampling: Day -4 (before, 30m and 4hrs after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30m and 4hrs after Amphinex), C5-D1, and C5-D8

Population: Maximum observed concentration (Cmax) was performed for patients in arm A.

A non-compartmental analysis (NCA) was applied on the data.

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=13 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 101-01 1st dose	2462 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 101-01 2nd dose	2377 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 101-02	2631 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 101-03 1st dose	2495 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 101-03 2nd dose	3172 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 106-01 1st dose (No samples taken before 90 hrs, Cmax value likely underestimated)	800 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 106-01 2nd dose	2923 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 111-02 1st dose	2221 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 111-02 2nd dose	3255 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 181-06 1st dose (No sample at 30 minutes, Cmax is likely underestimated)	1427 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 181-06 2nd dose	2321 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 183-03 1st dose	2624 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 183-03 2nd dose	2187 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 183-03 3rd dose	2571 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 187-02 1st dose	2750 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 187-02 2nd dose	1937 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 192-01	2017 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 303-01 1st dose	2606 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 303-01 2nd dose	1848 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 303-02 1st dose	2868 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 303-02 2nd dose	3124 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 401-01	2912 ng/ml	—
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. 501-01	2300 ng/ml	—

SECONDARY outcome

Timeframe: Timepoints for PK sampling: Day -4 (before, 30 min and 4 hours after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30 min and 4 hours after Amphinex) , C5-D1, and C5-D8

Population: A standard non-compartmental PK analysis (NCA) of bioanalytical data from 13 patients dosed with fimaporfin was performed for the RELEASE study.

A non-compartmental analysis (NCA) was applied on the data as described by Gabrielsson & Weiner (Methods in molecular biology, 929:161-180, 2012).

Outcome measures

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=13 Participants Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 401-01	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 501-01	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 101-01 1st dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 101-01 2nd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 101-02	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 101-03 1st dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 101-03 2nd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 106-01 1st dose (No samples taken before 90 hrs, erroneous data)	90 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 106-01 2nd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 111-02 1st dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 111-02 2nd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 181-06 1st dose (No sample at 30 minutes)	4 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 181-06 2nd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 183-03 1st dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 183-03 2nd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 183-03 3rd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 187-02 1st dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 187-02 2nd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 192-01	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 303-01 1st dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 303-01 2nd dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 303-02 1st dose	0.50 hours	—
Time to Cmax (Tmax) Was Performed for Patients in Arm A. 303-02 2nd dose	0.50 hours	—

SECONDARY outcome

Timeframe: Up to 18 months

Population: The RELEASE study did not collect QoL data.

QoL assessment. Patients select one of four answers to 22 questions ranging from 1 (not at all) to 4 (very much). Lower total scores indicate a more favorable QoL perception than a higher score.

Outcome measures

Outcome data not reported

Adverse Events

PCI Treatment in Conjunction With Standard of Care (SoC)

Serious events: 12 serious events

Other events: 18 other events

Deaths: 7 deaths

Standard of Care (SoC)

Serious events: 8 serious events

Other events: 16 other events

Deaths: 2 deaths

Serious adverse events

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=18 participants at risk Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=16 participants at risk Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Gastrointestinal disorders Duodenal ulcer	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Gastrointestinal disorders Pancreatitis acute	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
General disorders Pyrexia	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Investigations Aspartate aminotransferase increased	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Investigations Transaminases increased	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Hepatobiliary disorders Cholangitis	33.3% 6/18 • Number of events 9 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	18.8% 3/16 • Number of events 7 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Hepatobiliary disorders Cholangitis acute	0.00% 0/18 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	12.5% 2/16 • Number of events 2 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Hepatobiliary disorders Biliary obstruction	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Hepatobiliary disorders Cholecystitis	0.00% 0/18 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Infections and infestations Biliary tract infection	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Infections and infestations COVID-19	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Infections and infestations Cholangitis infective	5.6% 1/18 • Number of events 2 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Infections and infestations Sepsis	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Product Issues Stent malfunction	11.1% 2/18 • Number of events 4 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 2 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Product Issues Device occlusion	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Vascular disorders Aortic stenosis	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Vascular disorders Aortic thrombosis	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Nervous system disorders Toxic encephalopathy	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.

Other adverse events

Measure	PCI Treatment in Conjunction With Standard of Care (SoC) n=18 participants at risk Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given. Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.	Standard of Care (SoC) n=16 participants at risk Arm B: Gemcitabine/cisplatin chemotherapy Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Gastrointestinal disorders Gastrointestinal disorders	55.6% 10/18 • Number of events 30 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	75.0% 12/16 • Number of events 35 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
General disorders General disorders and administration site conditions	50.0% 9/18 • Number of events 13 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	50.0% 8/16 • Number of events 13 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Investigations Investigations	33.3% 6/18 • Number of events 45 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 10 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Blood and lymphatic system disorders Blood and lymphatic system disorders	5.6% 1/18 • Number of events 8 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	18.8% 3/16 • Number of events 12 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Hepatobiliary disorders Hepatobiliary disorders	22.2% 4/18 • Number of events 8 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	18.8% 3/16 • Number of events 6 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	44.4% 8/18 • Number of events 16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	18.8% 3/16 • Number of events 6 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Metabolism and nutrition disorders Metabolism and nutrition disorders	16.7% 3/18 • Number of events 7 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	37.5% 6/16 • Number of events 7 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Infections and infestations Infections and infestations	27.8% 5/18 • Number of events 8 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Nervous system disorders Nervous system disorders	33.3% 6/18 • Number of events 9 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	22.2% 4/18 • Number of events 9 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	0.00% 0/18 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	25.0% 4/16 • Number of events 5 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Product Issues Product issues	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Renal and urinary disorders Renal and urinary disorders	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	18.8% 3/16 • Number of events 3 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Vascular disorders Vascular disorders	0.00% 0/18 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Eye disorders Eye disorders	11.1% 2/18 • Number of events 2 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Psychiatric disorders Psychiatric disorders	11.1% 2/18 • Number of events 2 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	0.00% 0/18 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	12.5% 2/16 • Number of events 2 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Cardiac disorders Cardiac disorders	5.6% 1/18 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	0.00% 0/16 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.
Ear and labyrinth disorders Ear and labyrinth disorders	0.00% 0/18 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.	6.2% 1/16 • Number of events 1 • Adverse Events were monitored/assessed during chemotherapy, an average of 128.3 days (range 28 to 203 days). All-Cause Mortality was monitored/assessed up to 24 months. A total of 41 participants were randomised and included in the intent-to-treat (ITT) analysis set, with 34 participants being included in the safety analysis set (18 in Arm A and 16 in Arm B) and 34 participants being included in the mITT analysis set (19 in Arm A and 15 in Arm B). The difference in the number of participants in each arm between the safety analysis set and the mITT is due to 1 participant who was randomized to Arm A but received Arm B treatment.

Additional Information

Chief Executive Officer

PCI Biotech AS

Phone: (+47) 67 11 54 00

Email: post@pcibiotech.no

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place