Trial Outcomes & Findings for Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer (NCT NCT02077881)

NCT ID: NCT02077881

Last Updated: 2026-04-03

Results Overview

Phase 1 component: To identify the regimen limiting toxicity (RLT) for the combination of the immunotherapeutic agent indoximod when administered in combination with standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas. RLT will be considered as only grade 3 and 4 toxicities that are attributable to the test agent and result in the delay of the administration of the backbone chemotherapy, gemcitabine plus nab-paclitaxel.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

157 participants

Primary outcome timeframe

10 months

Results posted on

2026-04-03

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1 Dose Level 1 Participants received 600mg indoximod PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.	Phase 1 Dose Level 2 Participants received 1000mg indoximod PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.	Phase 1 Dose Level 3 Participants received 1200mg indoximod PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.	Indoximod and Gemcitabine + Nab-paclitaxel - Phase 2 Oral indoximod 1200mg BID concurrent with the first backbone chemotherapy cycle. Patients will receive gemcitabine plus nab-paclitaxel on a standard 4 week cycle schedule. Oral indoximod at 1200mg BID will continue throughout. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.
Overall Study STARTED	6	3	6	135
Overall Study COMPLETED	6	3	6	135
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1 Dose Level 1 n=6 Participants Participants received indoximod 600mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Phase 1 Dose Level 2 n=3 Participants Participants received indoximod 1000mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Phase 1 Dose Level 3 n=6 Participants Participants received indoximod 1200mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Indoximod and Gemcitabine + Nab-paclitaxel - Phase 2 n=135 Participants Oral indoximod 1200mg BID concurrent with the first backbone chemotherapy cycle. Patients will receive gemcitabine plus nab-paclitaxel on a standard 4 week cycle schedule. Oral indoximod at 1200mg BID will continue throughout. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Total n=150 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 11.88 • n=5 Participants	64.7 years STANDARD_DEVIATION 4.93 • n=5 Participants	67.5 years STANDARD_DEVIATION 10.05 • n=10 Participants	63.9 years STANDARD_DEVIATION 9.76 • n=5 Participants	64 years STANDARD_DEVIATION 9.73 • n=11 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=5 Participants	0 Participants n=10 Participants	73 Participants n=5 Participants	78 Participants n=11 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=5 Participants	6 Participants n=10 Participants	62 Participants n=5 Participants	72 Participants n=11 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=10 Participants	1 Participants n=5 Participants	2 Participants n=11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=5 Participants	6 Participants n=10 Participants	118 Participants n=5 Participants	131 Participants n=11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=10 Participants	16 Participants n=5 Participants	17 Participants n=11 Participants
Weight	72.5 Kilograms STANDARD_DEVIATION 12.7402 • n=5 Participants	77.9 Kilograms STANDARD_DEVIATION 4.2439 • n=5 Participants	90 Kilograms STANDARD_DEVIATION 10.8966 • n=10 Participants	78.650 Kilograms STANDARD_DEVIATION 17.0573 • n=5 Participants	78.818 Kilograms STANDARD_DEVIATION 16.6515 • n=11 Participants
Height	167.0 centimeters STANDARD_DEVIATION 8.76 • n=5 Participants	169.6 centimeters STANDARD_DEVIATION 1.75 • n=5 Participants	176.7 centimeters STANDARD_DEVIATION 10.38 • n=10 Participants	170.4 centimeters STANDARD_DEVIATION 9.68 • n=5 Participants	170.4 centimeters STANDARD_DEVIATION 9.61 • n=11 Participants
BMI	26.2 kg/m2 STANDARD_DEVIATION 2.96 • n=5 Participants	27.1 kg/m2 STANDARD_DEVIATION 1.07 • n=5 Participants	29.6 kg/m2 STANDARD_DEVIATION 3.94 • n=10 Participants	26.9 kg/m2 STANDARD_DEVIATION 4.83 • n=5 Participants	27.0 kg/m2 STANDARD_DEVIATION 4.69 • n=11 Participants
BSA	1.8 m^2 STANDARD_DEVIATION 0.20 • n=5 Participants	1.9 m^2 STANDARD_DEVIATION 0.06 • n=5 Participants	2.1 m^2 STANDARD_DEVIATION 0.16 • n=10 Participants	1.9 m^2 STANDARD_DEVIATION 0.24 • n=5 Participants	1.9 m^2 STANDARD_DEVIATION 0.24 • n=11 Participants
Baseline ECOG Performance Status	0.8 units on a scale STANDARD_DEVIATION 0.41 • n=5 Participants	0.3 units on a scale STANDARD_DEVIATION 0.58 • n=5 Participants	0.7 units on a scale STANDARD_DEVIATION 0.52 • n=10 Participants	0.3 units on a scale STANDARD_DEVIATION 0.47 • n=5 Participants	0.4 units on a scale STANDARD_DEVIATION 0.48 • n=11 Participants

PRIMARY outcome

Timeframe: 10 months

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 1 n=6 Participants Indoximod 600mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2	Phase 1 Dose Level 2 n=3 Participants Indoximod 1000mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2	Phase 1 Dose Level 3 n=6 Participants Indoximod 1200mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2
Regimen Limiting Toxicity	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 22 months

Phase 2 component: To evaluate efficacy as determined by overall survival (OS) in patients with metastatic adenocarcinoma of the pancreas.

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 1 n=103 Participants Indoximod 600mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2	Phase 1 Dose Level 2 n=135 Participants Indoximod 1000mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2	Phase 1 Dose Level 3 Indoximod 1200mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2
Overall Survival	47.9 Weeks Interval 40.3 to 59.3	39.1 Weeks Interval 31.9 to 47.3	—

SECONDARY outcome

Timeframe: 22 months

To determine the response rate of the combination indoximod with gemcitabine plus nab-paclitaxel. Imaging assessments to be performed at protocol-specified time points and evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 1 n=103 Participants Indoximod 600mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2	Phase 1 Dose Level 2 n=135 Participants Indoximod 1000mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2	Phase 1 Dose Level 3 Indoximod 1200mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2
Response Rate Complete Response	2 Participants	2 Participants	—
Response Rate Partial Response	46 Participants	46 Participants	—
Response Rate No Response	55 Participants	87 Participants	—

SECONDARY outcome

Timeframe: 22 months

Time to progression with the combination indoximod with gemcitabine plus nab-paclitaxel. Progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

Outcome measures

Outcome measures
Measure	Phase 1 Dose Level 1 n=103 Participants Indoximod 600mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2	Phase 1 Dose Level 2 n=128 Participants Indoximod 1000mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2	Phase 1 Dose Level 3 Indoximod 1200mg PO BID with IV Nab-Paclitaxel 125mg/m\^2 followed by gemcitabine 1000 mg/m\^2
Progression Free Survival	32.1 Weeks Interval 25.1 to 35.0	26.6 Weeks Interval 22.1 to 32.3	—

Adverse Events

Phase 1 Dose Level 1

Serious events: 2 serious events

Other events: 6 other events

Deaths: 1 deaths

Phase 1 Dose Level 2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 1 Dose Level 3

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Indoximod and Gemcitabine + Nab-paclitaxel - Phase 2

Serious events: 84 serious events

Other events: 135 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Lumos Pharma, Inc.

Phone: 515-598-2921

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Phase 1 Dose Level 1 n=6 participants at risk Participants received indoximod 600mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Phase 1 Dose Level 2 n=3 participants at risk Participants received indoximod 1000mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Phase 1 Dose Level 3 n=6 participants at risk Participants received indoximod 1200mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Indoximod and Gemcitabine + Nab-paclitaxel - Phase 2 n=135 participants at risk Oral indoximod 1200mg BID concurrent with the first backbone chemotherapy cycle. Patients will receive gemcitabine plus nab-paclitaxel on a standard 4 week cycle schedule. Oral indoximod at 1200mg BID will continue throughout. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	3.0% 4/135 • Number of events 4 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	2.2% 3/135 • Number of events 3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Atrial fibrillation	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Cardiac failure	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Cardiac arrest	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Myocardial infarction	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Pericardial effusion	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Ascites	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	3.7% 5/135 • Number of events 5 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	3.7% 5/135 • Number of events 5 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Colitis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	2.2% 3/135 • Number of events 3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Duodenal obstruction	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Duodenitis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Gastrointestinal necrosis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Nausea	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Obstruction gastric	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Pancreatitis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
General disorders Pyrexia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	3.7% 5/135 • Number of events 5 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
General disorders Oedema	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	2.2% 3/135 • Number of events 3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
General disorders Fatigue	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
General disorders Mucosal inflammation	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
General disorders Sudden death	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
General disorders Influenza like illness	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Hepatobiliary disorders Cholangitis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Hepatobiliary disorders Liver injury	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Immune system disorders Drug hypersensitivity	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Infections and infestations Sepsis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	6.7% 9/135 • Number of events 9 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.

Other adverse events
Measure	Phase 1 Dose Level 1 n=6 participants at risk Participants received indoximod 600mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Phase 1 Dose Level 2 n=3 participants at risk Participants received indoximod 1000mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Phase 1 Dose Level 3 n=6 participants at risk Participants received indoximod 1200mg PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.	Indoximod and Gemcitabine + Nab-paclitaxel - Phase 2 n=135 participants at risk Oral indoximod 1200mg BID concurrent with the first backbone chemotherapy cycle. Patients will receive gemcitabine plus nab-paclitaxel on a standard 4 week cycle schedule. Oral indoximod at 1200mg BID will continue throughout. Nab-Paclitaxel: Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Gemcitabine: Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity. Indoximod: Indoximod administered BID by mouth in the form of 200 mg capsules. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.
Cardiac disorders Myocardial infarction	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Eye disorders Vision blurred	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	5.2% 7/135 • Number of events 7 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Eye disorders Visual impairment	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	33.3% 1/3 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Haemolytic uraemic syndrome	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Splenic vein thrombosis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Eye disorders Lacrimation increased	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Diastolic dysfunction	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Mitral valve sclerosis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Leukopenia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Anaemia	66.7% 4/6 • Number of events 4 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	48.1% 65/135 • Number of events 65 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Neutropenia	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	50.0% 3/6 • Number of events 3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	8.9% 12/135 • Number of events 12 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	6.7% 9/135 • Number of events 9 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	4.4% 6/135 • Number of events 6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	2.2% 3/135 • Number of events 3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	2.2% 3/135 • Number of events 3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Atrial fibrillation	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	33.3% 1/3 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	4.4% 6/135 • Number of events 6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Sinus tachycardia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	5.2% 7/135 • Number of events 7 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Cardiac failure	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	3.7% 5/135 • Number of events 5 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Pericardial effusion	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	3.0% 4/135 • Number of events 4 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Tachycardia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	3.7% 5/135 • Number of events 5 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Sinus bradycardia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	2.2% 3/135 • Number of events 3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Acute myocardial infarction	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Aortic valve stenosis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Arrhythmia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Cardiac arrest	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Cardiac failure congestive	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Left ventricular dysfunction	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Mitral valve incompetence	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Supraventricular tachycardia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Tricuspid valve incompetence	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Cardiac disorders Ventricular tachycardia	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Ear and labyrinth disorders Vertigo	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	1.5% 2/135 • Number of events 2 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Ear and labyrinth disorders Ear congestion	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Ear and labyrinth disorders Ear haemorrhage	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Ear and labyrinth disorders Hypoacusis	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Eye disorders Dry eye	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	16.7% 1/6 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/135 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.
Eye disorders Eye pain	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/3 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.00% 0/6 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.	0.74% 1/135 • Number of events 1 • Adverse events were captured from the first dose of study drug through study completion up to 26 months.