Trial Outcomes & Findings for A Study of LY2090314 and Chemotherapy in Participants With Metastatic Pancreatic Cancer (NCT NCT01632306)

Last Updated: 2019-01-15

Results Overview

Change in the phosphorylation level of glycogen synthase, a glycogen synthase kinase-3 beta (GSK-3beta) inhibitor, from baseline to 4 hours post-treatment on day 0 using tumor tissue and blood specimens.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Baseline, 4 Hours Post-Treatment on Day 0

Results posted on

2019-01-15

Participant Flow

Participant milestones

Participant milestones
Measure	LY2090314 + Gemcitabine LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.
Overall Study STARTED	3	10
Overall Study Received at Least One Dose of Study Drug	3	10
Overall Study COMPLETED	2	10
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	LY2090314 + Gemcitabine LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.	LY2090314 + Gemcitabine + Nab-paclitaxel LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 mg/m² gemcitabine + 125 mg/m² nab-paclitaxel given IV on days 1, 8 and 15 in 28-day cycle. New cohort opened per protocol amendment.
Overall Study Protocol Violation	1	0	0

Baseline Characteristics

A Study of LY2090314 and Chemotherapy in Participants With Metastatic Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY2090314 + Gemcitabine n=3 Participants LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX n=10 Participants LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.	Total n=13 Participants Total of all reporting groups
Age, Continuous	60.7 years STANDARD_DEVIATION 8.5 • n=5 Participants	64.0 years STANDARD_DEVIATION 4.9 • n=7 Participants	63.2 years STANDARD_DEVIATION 5.7 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	10 participants n=7 Participants	13 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 4 Hours Post-Treatment on Day 0

Population: Zero participants analyzed. GSK3β phosphorylation levels were not determined, and the primary endpoint was not examined as there wasn't viable tumor tissue for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Date of Death Due to any Cause Up to 21 Months

Population: All the participants that received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	LY2090314 + Gemcitabine n=3 Participants LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX n=10 Participants LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.
Overall Survival (OS)	1.8 Months Interval 1.3 to 1.9	7.7 Months Interval 2.9 to 21.2

SECONDARY outcome

Timeframe: Baseline to Date of Death to any cause Up to 6 Months

Population: All participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	LY2090314 + Gemcitabine n=3 Participants LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX n=10 Participants LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.
Percentage of Participants Who Survived at 6 Months	0 Percentage of participants Interval 0.0 to 0.0	50.0 Percentage of participants Interval 26.9 to 92.9

SECONDARY outcome

Timeframe: Baseline to Disease Progression Up to 18 Months

Population: All participants who received at least one dose of study drug.

PFS was as the time from enrollment to the earliest documented evidence of disease progression or death,whatever comes first.

Outcome measures

Outcome measures
Measure	LY2090314 + Gemcitabine n=3 Participants LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX n=10 Participants LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.
Progression Free Survival (PFS)	1.8 Months Interval 1.3 to 1.9	3.4 Months Interval 2.3 to 17.5

SECONDARY outcome

Timeframe: Baseline Up to 6 Months

Population: All participants who received at least one dose of study drug.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size \[\<10 millimeter (mm) short axis\]. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100. A CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.

Outcome measures

Outcome measures
Measure	LY2090314 + Gemcitabine n=3 Participants LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX n=10 Participants LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]	0 Percentage of Participants There were "0" participants with CR or PR.	10.0 Percentage of Participants Interval 0.3 to 44.5

Adverse Events

LY2090314 + Gemcitabine

Serious events: 3 serious events

Other events: 2 other events

Deaths: 0 deaths

LY2090314 + FOLFOX

Serious events: 7 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	LY2090314 + Gemcitabine n=3 participants at risk LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX n=10 participants at risk LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Anorexia	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Ascites	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/10 All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/10 All participants who received at least one dose of study drug.
Hepatobiliary disorders Gallbladder obstruction	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastric fistula	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/10 All participants who received at least one dose of study drug.
General disorders Failure to Thrive	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Vascular disorders Hypotension	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Clostridium difficle infection	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Lung infection	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 3 All participants who received at least one dose of study drug.
Infections and infestations Peritoneal infection	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/10 All participants who received at least one dose of study drug.
Investigations Platelet count decreased	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Sepsis	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/10 All participants who received at least one dose of study drug.
Infections and infestations Skin infection	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/10 All participants who received at least one dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/10 All participants who received at least one dose of study drug.
Vascular disorders Thromboembolic event	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 3 All participants who received at least one dose of study drug.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Vascular disorders Pulmonary embolism	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.

Measure	LY2090314 + Gemcitabine n=3 participants at risk LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.	LY2090314 + FOLFOX n=10 participants at risk LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.
Gastrointestinal disorders Abdominal pain	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	80.0% 8/10 • Number of events 25 All participants who received at least one dose of study drug.
Endocrine disorders Adrenal insufficiency	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Akathisia	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 7 All participants who received at least one dose of study drug.
Investigations Alanine aminotransferase	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	40.0% 4/10 • Number of events 11 All participants who received at least one dose of study drug.
Investigations Alkaline phosphatase	0.00% 0/3 All participants who received at least one dose of study drug.	30.0% 3/10 • Number of events 7 All participants who received at least one dose of study drug.
Immune system disorders Allergic reaction	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 2 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 6 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 All participants who received at least one dose of study drug.	30.0% 3/10 • Number of events 6 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 3 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	40.0% 4/10 • Number of events 14 All participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 2 All participants who received at least one dose of study drug.
Gastrointestinal disorders Ascites	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 4 All participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	40.0% 4/10 • Number of events 8 All participants who received at least one dose of study drug.
Gastrointestinal disorders Bloating	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Eye disorders Blurred vision	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 6 All participants who received at least one dose of study drug.
Investigations Cardiac troponin T increased	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Cognitive disturbance	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 2 All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/3 All participants who received at least one dose of study drug.	30.0% 3/10 • Number of events 13 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 5 All participants who received at least one dose of study drug.
Investigations Creatinine increased	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 2 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	40.0% 4/10 • Number of events 14 All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 7 All participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 9 All participants who received at least one dose of study drug.
Investigations ECG QT corrected interval prolonged	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	50.0% 5/10 • Number of events 5 All participants who received at least one dose of study drug.
General disorders Edema limbs	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 2 All participants who received at least one dose of study drug.
General disorders Edema trunk	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Esophageal pain	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 2 All participants who received at least one dose of study drug.
General disorders Fatigue	0.00% 0/3 All participants who received at least one dose of study drug.	90.0% 9/10 • Number of events 30 All participants who received at least one dose of study drug.
General disorders Fever	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 4 All participants who received at least one dose of study drug.
Gastrointestinal disorders Flatulence	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 8 All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 2 All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 9 All participants who received at least one dose of study drug.
General disorders night sweats	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Headache	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 7 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminemia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 8 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 2 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 5 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 8 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 3 All participants who received at least one dose of study drug.
Vascular disorders Hypotension	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Investigations Elevated lactic acid	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Mucosal infection	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Mucositis oral	0.00% 0/3 All participants who received at least one dose of study drug.	30.0% 3/10 • Number of events 9 All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	60.0% 6/10 • Number of events 26 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death due to disease progression	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/10 All participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	0.00% 0/3 All participants who received at least one dose of study drug.	30.0% 3/10 • Number of events 10 All participants who received at least one dose of study drug.
General disorders Pain	0.00% 0/3 All participants who received at least one dose of study drug.	20.0% 2/10 • Number of events 3 All participants who received at least one dose of study drug.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 7 All participants who received at least one dose of study drug.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 All participants who received at least one dose of study drug.	40.0% 4/10 • Number of events 21 All participants who received at least one dose of study drug.
Investigations Platelet count decreased	0.00% 0/3 All participants who received at least one dose of study drug.	50.0% 5/10 • Number of events 23 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 8 All participants who received at least one dose of study drug.
Investigations White blood cell	0.00% 0/3 All participants who received at least one dose of study drug.	10.0% 1/10 • Number of events 6 All participants who received at least one dose of study drug.