Trial Outcomes & Findings for Gemcitabine, Cisplatin, Plus Lenalidomide as First-line Therapy for Patients With Metastatic Urothelial Carcinoma (NCT NCT01342172)

Last Updated: 2019-04-23

Results Overview

MTD was determined by testing planned increasing doses up to 25 mg daily dose on days 1-14, starting at 10mg. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined as any lenalidomide-related Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) Grade 3 or 4 adverse events

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

9 participants

Primary outcome timeframe

after 1 cycle (each cycle is 21 days)

Results posted on

2019-04-23

Participant Flow

The study opened to accrual at the Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah; the National Cancer Institute, Bethesda, Maryland;, and the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NewYork over the course of 19 months.

Participant milestones

Participant milestones
Measure	Lenalidomide lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Gemcitabine, Cisplatin, Plus Lenalidomide as First-line Therapy for Patients With Metastatic Urothelial Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenalidomide n=9 Participants lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC
Age, Continuous	69 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
ECOG Performance Status 0	0 Participants n=5 Participants
ECOG Performance Status 1	8 Participants n=5 Participants
ECOG Performance Status 2	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: after 1 cycle (each cycle is 21 days)

Population: The dose of lenalidomide was not escalated beyond 10 mg because of cytopenias requiring repeated dose delays and reductions.

Outcome measures

Outcome measures
Measure	Lenalidomide n=9 Participants lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC
Maximum Tolerated Dose (MTD) of Lenalidomide	10 mg

PRIMARY outcome

Timeframe: 1 year

Population: Data not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After 2 cycles (a cycle is 21 days)

The objective response rate as determined by Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) Disappearance of all target lesions for a period of at least one month. Partial Response (PR) At least a 30% decrease in the sum of the longest diameter of measures lesions (target lesions), taking as reference the baseline sum of the longest diameter. Stable Disease (NR/SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since the treatment started. Progressive Disease (PD) A 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions), taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

Outcome measures

Outcome measures
Measure	Lenalidomide n=9 Participants lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC
The Objective Response Rate to Treatment With Gemcitabine, Cisplatin, Plus Lenalidomide CR	1 Participants
The Objective Response Rate to Treatment With Gemcitabine, Cisplatin, Plus Lenalidomide PR	2 Participants
The Objective Response Rate to Treatment With Gemcitabine, Cisplatin, Plus Lenalidomide SD	3 Participants
The Objective Response Rate to Treatment With Gemcitabine, Cisplatin, Plus Lenalidomide PD	2 Participants
The Objective Response Rate to Treatment With Gemcitabine, Cisplatin, Plus Lenalidomide not evaluable	1 Participants

SECONDARY outcome

Timeframe: Day 1 and Day 8 of each treatment cycle; 21 days after the last dose of Lenalidomide

Number of grade \>=3 adverse events to assess the safety of combination therapy with gemcitabine, cisplatin plus lenalidomide as determined by the frequency and severity of adverse events as per the NCI Common Terminology for Adverse Events (CTCAE) version 4.0.

Outcome measures

Outcome measures
Measure	Lenalidomide n=9 Participants lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC
Number of Grade >=3 Adverse Events Grade 3	28 events
Number of Grade >=3 Adverse Events Grade 4	7 events

SECONDARY outcome

Timeframe: 168 days

Best Overall Response to evaluate lenalidomide as maintenance treatment in patients achieving an objective response of either complete response or partial response following completion of 6 cycles of combination therapy. Complete Response (CR) - CR of target lesions and no new lesions Partial Response (PR) -PR of target lesions and no new lesions Stable Disease (SD) - SD of target lesions and no new lesions Progression Disease (PD) - any status of target lesions and new lesions

Outcome measures

Outcome measures
Measure	Lenalidomide n=9 Participants lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC
Best Overall Response CR	1 Participants
Best Overall Response PR	2 Participants

SECONDARY outcome

Timeframe: Day 1 of Cycle 0 and Day 1 of Cycle 2 (each Cycle is 21 days)

Population: Data not collected

To determine the changes in cellular immunity with lenalidomide in peripheral blood mononuclear cells including Tregs, NK, NKT cells (Berg et al JCO 2010), sIl-2R, TNF alpha (Bartlett et al BJC 2004) and markers indicative of activation, i.e. CD107a. These analyses will only be done in the phase II portion of the protocol.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 of Cycles 0, 1 and 2 (each Cycle is 21 days)

Population: Data not collected.

Circulating epithelial tumor cells (CTC) will be investigated as an experimental endpoint using immunofluorescence techniques and CTC identification by positive expression of epithelial markers and a viability marker and negative expression of hematopoietic markers. These analyses will only be done in the phase II portion of the protocol.

Outcome measures

Outcome data not reported

Adverse Events

Lenalidomide for Cycle 1

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Phase 2

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lenalidomide for Cycle 1 n=9 participants at risk lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC	Phase 2 n=9 participants at risk lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC
Blood and lymphatic system disorders Thrombocytopenia	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher

Other adverse events

Additional Information

Dr. Matthew Galsky

Icahn School of Medicine at Mount Sinai

Phone: 212-241-8816

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Lenalidomide for Cycle 1 n=9 participants at risk lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC	Phase 2 n=9 participants at risk lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC
Gastrointestinal disorders Abdominal Pain	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders ALP/ALT increase	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Blood and lymphatic system disorders Anemia	33.3% 3/9 • Number of events 3 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Hepatobiliary disorders Ascending Cholangitis	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Eye disorders Blurred Vision	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Nervous system disorders Confusion	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Dehydration	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Diarrhea	22.2% 2/9 • Number of events 2 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	66.7% 6/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Fatigue	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	44.4% 4/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Immune system disorders Febrile neutropenia	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Hypocalcemia	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Hypokalemia	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Hypomagnesium	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Hyponatremia	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Blood and lymphatic system disorders Leukopenia	33.3% 3/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Blood and lymphatic system disorders Neutropenia	77.8% 7/9 • Number of events 7 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Blood and lymphatic system disorders Pancytopenia	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Blood and lymphatic system disorders thrombocytopenia	44.4% 4/9 • Number of events 4 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	55.6% 5/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Renal and urinary disorders Urinary tract infection	11.1% 1/9 • Number of events 1 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	33.3% 3/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Angular Chelitis	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Anorexia	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	33.3% 3/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Bone pain	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders C. difficile infection	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Cold	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Constipation	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	77.8% 7/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	55.6% 5/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Renal and urinary disorders Creatinine increased	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	44.4% 4/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Dizziness	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	44.4% 4/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Dry Mouth	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Edema	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	44.4% 4/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Skin and subcutaneous tissue disorders Erythematous rash	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Fever	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Flu-like symptoms	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Hand Tremors	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Ear and labyrinth disorders Hearing Loss	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Renal and urinary disorders Hematuria	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	33.3% 3/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Nervous system disorders Hydrocephalus	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Hypernatremia	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Hypertension	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Lightheadedness	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Loss of appetitie	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Lower back pain	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Mouth sores	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Mucositis	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Nausea	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	88.9% 8/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Nervous system disorders Neuropathy	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	66.7% 6/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Oral Thrush	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Pain extremities	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	44.4% 4/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Vascular disorders Phlebitis	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Pruritus	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Rhinorrhea	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Nervous system disorders Right-heel numbness	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Sore Throat	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Cardiac disorders Syncope	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Cardiac disorders Tachycardia	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Taste alteration	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Vascular disorders Thromboembolism	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	44.4% 4/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Ear and labyrinth disorders Tinnitus	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	22.2% 2/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Renal and urinary disorders Urinary frequency	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Renal and urinary disorders Urinary hesitancy	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Gastrointestinal disorders Vomiting	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	88.9% 8/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
Eye disorders Watering eye left	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher
General disorders Weakness	0.00% 0/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher	11.1% 1/9 • Adverse event data collected over the course of 19 months Listed are adverse events with grade 3 or higher