A Study of LY2510924 and Durvalumab in Participants With Solid Tumors

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02737072
• Collaborator: AstraZeneca (Industry)
• Enrollment: 9
• Arms: 3
• Duration (Months): 12.8

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the safety and tolerability of chemokine (C-X-C Motif) receptor 4 (CXCR4) peptide antagonist LY2510924 and durvalumab for phase 1a and 1b in participants with advanced refractory solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor	Drug: LY2510924; Drug: Durvalumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1a/1b Study of CXCR4 Peptide Antagonist (LY2510924) Administered in Combination With the Anti-PD-L1 Antibody, Durvalumab (MEDI4736), in Advanced Refractory Solid Tumors
• Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Sep 25, 2017
• Actual Study Completion Date: Sep 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 20 mg LY2510924 + 1500 mg Durvalumab 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	Drug: LY2510924; Administered SQ; Drug: Durvalumab; Administered IV
Experimental: 30 mg LY2510924 + 1500 mg Durvalumab 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	Drug: LY2510924; Administered SQ; Drug: Durvalumab; Administered IV
Experimental: 40 mg LY2510924 + 1500 mg Durvalumab 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	Drug: LY2510924; Administered SQ; Drug: Durvalumab; Administered IV

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [Cycle 1 (28 Days)]

   DLT is defined as 1 of the following adverse events(AE) reported during the Phase 1a DLT observation period,if considered to be definitely,probably,or possibly related to either study regimen by the investigator;and fulfills any 1 of the following criterion using(NCI)CTCAE version(v)4.03:Grade4 immune-related AE,Grade4 non-laboratory AE,any CTCAE Grade ≥3 QT prolongation AE,≥Grade3 colitis or noninfectious pneumonitis irrespective of duration,Grade3 immune-related AE(excluding colitis,QT prolongation,or pneumonitis) that does not downgrade to Grade2 within 3 days after onset of event despite optimal medical management including systemic corticosteroids,or does not downgrade to ≤Grade 1 or baseline within 14 days,Grade2 pneumonitis that does not resolve to ≤Grade 1 within 3 days of the initiation of maximal supportive care,including corticosteroid therapy,Grade3 toxicity lasting an extended time despite optimal supportive care and there were also laboratory abnormalities criterion.

2. Maximum Tolerated Dose (MTD) of LY2510924 [Cycle 1 (28 Days)]

   MTD was determined after the evaluation of Phase 1a portion of the trial. For Phase 1a, any DLT-equivalent toxicities observed in Cycle 2 and beyond were also be considered in dose escalation and determining MTD/recommended Phase 2 dose. See outcome measure number 1 for the DLT criterion.

Secondary Outcome Measures

1. Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 When Co-Administered With Durvalumab [Cycle 1 Day 1: Predose, 0.5, 2, 4, 6, 8, 24-30 hours; Day 15: Predose, 0.5, 2, 4, 6, 8 hours]

   Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 when Co-Administered with Durvalumab

2. Number of Participants With Anti-Durvalumab Antibodies When Administered in Combination With LY2510924 [Predose Cycle 1 Day 1 through 90 Day Post Treatment Follow Up (Up To 12 Months)]

   Number of participants with treatment-emergent positive Anti-Durvalumab antibodies was summarized by treatment group.

3. Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] [Baseline through Measured Progressive Disease or Death (Up To 12 Months)]

   Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in sum of diameter(SOD) of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100.

4. Percentage of Participants With CR, PR, or Stable Disease (SD) (Disease Control Rate [DCR]) [Baseline through Measured Progressive Disease (Up To 12 Months)]

   DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in sum of diameter (SOD) of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)*100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Phase 1a: Have histologic or cytologic confirmation of advanced solid tumor

• Have at least 1 measurable lesion assessable using standard techniques by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

• Have adequate organ function

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have provided tissue from a newly obtained core or excisional biopsy of a tumor lesion or a recent biopsy defined by ≤3 years since last documented progression of disease

• Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator

Exclusion Criteria:

• Have a serious concomitant systemic disorder including human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active HCV, active autoimmune disorder or disease requiring high dose of steroids

• Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection or chronic diarrhea

• Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis

• Have an active infection requiring systemic therapy

• Have had prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-PD-L2, or anticytotoxic T lymphocyte-associated antigen-4 antibody

• Moderate or severe cardiovascular disease

• Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment

• Have received a live vaccine within 30 days before the first dose of study treatment

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Eli Lilly and Company
• AstraZeneca

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Oct 12, 2016
• Statistical Analysis Plan - Jun 2, 2017

More Information

Additional Information:

• Click here for more information about this study: A Study of LY2510924 and Durvalumab in Participants With Solid Tumors

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02737072
• Other Study ID Numbers: 16387; I2V-MC-CXAD
• First Posted: Apr 13, 2016
• Last Update Posted: Aug 12, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Eli Lilly and Company: immuno-oncology
• Additional relevant MeSH terms: Neoplasms; Durvalumab

Study Results

Participant Flow

Pre-assignment Detail	This study was conducted in 2 parts. Phase 1a of the study consisted of a dose-escalation assessment and Phase 1b of the study included 2 expansion arms. The study was terminated after the Phase 1a part was complete. A participant completed the study if they completed at least 1 cycle.

Arm/Group Title	20 mg LY2510924 + 1500 mg Durvalumab	30 mg LY2510924 + 1500 mg Durvalumab	40 mg LY2510924 + 1500 mg Durvalumab
Arm/Group Description	20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Period Title: Overall Study
STARTED	3	3	3
Received at Least One Dose of Drug	3	3	3
COMPLETED	3	3	3
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	20 mg LY2510924 + 1500 mg Durvalumab	30 mg LY2510924 + 1500 mg Durvalumab	40 mg LY2510924 + 1500 mg Durvalumab	Total
Arm/Group Description	20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	Total of all reporting groups
Overall Participants	3	3	3	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.33 (22.12)	60.00 (7.55)	48.33 (3.21)	54.89 (12.88)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	2 66.7%	3 33.3%
Male	2 66.7%	3 100%	1 33.3%	6 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	3 100%	3 100%	9 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	3 100%	3 100%	3 100%	9 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	3 100%	3 100%	3 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Description	DLT is defined as 1 of the following adverse events(AE) reported during the Phase 1a DLT observation period,if considered to be definitely,probably,or possibly related to either study regimen by the investigator;and fulfills any 1 of the following criterion using(NCI)CTCAE version(v)4.03:Grade4 immune-related AE,Grade4 non-laboratory AE,any CTCAE Grade ≥3 QT prolongation AE,≥Grade3 colitis or noninfectious pneumonitis irrespective of duration,Grade3 immune-related AE(excluding colitis,QT prolongation,or pneumonitis) that does not downgrade to Grade2 within 3 days after onset of event despite optimal medical management including systemic corticosteroids,or does not downgrade to ≤Grade 1 or baseline within 14 days,Grade2 pneumonitis that does not resolve to ≤Grade 1 within 3 days of the initiation of maximal supportive care,including corticosteroid therapy,Grade3 toxicity lasting an extended time despite optimal supportive care and there were also laboratory abnormalities criterion.
Time Frame	Cycle 1 (28 Days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	20 mg LY2510924 + 1500 mg Durvalumab	30 mg LY2510924 + 1500 mg Durvalumab	40 mg LY2510924 + 1500 mg Durvalumab
Arm/Group Description	20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Measure Participants	3	3	3
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of LY2510924
Description	MTD was determined after the evaluation of Phase 1a portion of the trial. For Phase 1a, any DLT-equivalent toxicities observed in Cycle 2 and beyond were also be considered in dose escalation and determining MTD/recommended Phase 2 dose. See outcome measure number 1 for the DLT criterion.
Time Frame	Cycle 1 (28 Days)

Outcome Measure Data

Analysis Population Description

All phase 1a participants who received at least one dose of study drug.

Arm/Group Title	All Phase 1a Participants
Arm/Group Description	20 mg LY2510924 + 1500 mg Durvalumab: 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days). 30 mg LY2510924 + 1500 mg Durvalumab: 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days). 40 mg LY2510924 + 1500 mg Durvalumab: 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Measure Participants	3
Number [milligram (mg)]	40

3. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 When Co-Administered With Durvalumab
Description	Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 when Co-Administered with Durvalumab
Time Frame	Cycle 1 Day 1: Predose, 0.5, 2, 4, 6, 8, 24-30 hours; Day 15: Predose, 0.5, 2, 4, 6, 8 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	20 mg LY2510924 + 1500 mg Durvalumab	30 mg LY2510924 + 1500 mg Durvalumab	40 mg LY2510924 + 1500 mg Durvalumab
Arm/Group Description	20 milligrams (mg) LY2510924 given subcutaneously (SQ) in combination with 1500 mg durvalumab given intravenously (IV).	30 mg LY2510924 given SQ in combination with 1500 mg durvalumab given IV.	40 mg LY2510924 given SQ in combination with 1500 mg durvalumab given IV.
Measure Participants	3	3	3
Day 1	3390 (33)	3430 (17)	7490 (57)
Day 15	1960 (258)	4320 (11)	NA (NA)

4. Secondary Outcome

Title	Number of Participants With Anti-Durvalumab Antibodies When Administered in Combination With LY2510924
Description	Number of participants with treatment-emergent positive Anti-Durvalumab antibodies was summarized by treatment group.
Time Frame	Predose Cycle 1 Day 1 through 90 Day Post Treatment Follow Up (Up To 12 Months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	20 mg LY2510924 + 1500 mg Durvalumab	30 mg LY2510924 + 1500 mg Durvalumab	40 mg LY2510924 + 1500 mg Durvalumab
Arm/Group Description	20 milligrams (mg) LY2510924 given subcutaneously (SQ) in combination with 1500 mg durvalumab given intravenously (IV).	30 mg LY2510924 given SQ in combination with 1500 mg durvalumab given IV.	40 mg LY2510924 given SQ in combination with 1500 mg durvalumab given IV.
Measure Participants	3	3	3
Count of Participants [Participants]	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Description	Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in sum of diameter(SOD) of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100.
Time Frame	Baseline through Measured Progressive Disease or Death (Up To 12 Months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	20 mg LY2510924 + 1500 mg Durvalumab	30 mg LY2510924 + 1500 mg Durvalumab	40 mg LY2510924 + 1500 mg Durvalumab
Arm/Group Description	20 milligrams (mg) LY2510924 given subcutaneously (SQ) in combination with 1500 mg durvalumab given intravenously (IV).	30 mg LY2510924 given SQ in combination with 1500 mg durvalumab given IV.	40 mg LY2510924 given SQ in combination with 1500 mg durvalumab given IV.
Measure Participants	3	3	3
Number [percentage of participants]	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With CR, PR, or Stable Disease (SD) (Disease Control Rate [DCR])
Description	DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in sum of diameter (SOD) of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)*100.
Time Frame	Baseline through Measured Progressive Disease (Up To 12 Months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	20 mg LY2510924 + 1500 mg Durvalumab	30 mg LY2510924 + 1500 mg Durvalumab	40 mg LY2510924 + 1500 mg Durvalumab
Arm/Group Description	20 milligrams (mg) LY2510924 given subcutaneously (SQ) in combination with 1500 mg durvalumab given intravenously (IV).	30 mg LY2510924 given SQ in combination with 1500 mg durvalumab given IV.	40 mg LY2510924 given SQ in combination with 1500 mg durvalumab given IV.
Measure Participants	3	3	3
Number [percentage of participants]	100 3333.3%	33.3 1110%	0 0%

Adverse Events

Time Frame	Up To 14 months
Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	20 mg LY2510924 + 1500 mg Durvalumab		30 mg LY2510924 + 1500 mg Durvalumab		40 mg LY2510924 + 1500 mg Durvalumab
Arm/Group Description	20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).		30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).		40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
All Cause Mortality
	20 mg LY2510924 + 1500 mg Durvalumab		30 mg LY2510924 + 1500 mg Durvalumab		40 mg LY2510924 + 1500 mg Durvalumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		3/3 (100%)		1/3 (33.3%)
Serious Adverse Events
	20 mg LY2510924 + 1500 mg Durvalumab		30 mg LY2510924 + 1500 mg Durvalumab		40 mg LY2510924 + 1500 mg Durvalumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)
Blood and lymphatic system disorders
Neutropenia	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Nervous system disorders
Metabolic encephalopathy	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Vascular disorders
Vena cava thrombosis	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	20 mg LY2510924 + 1500 mg Durvalumab		30 mg LY2510924 + 1500 mg Durvalumab		40 mg LY2510924 + 1500 mg Durvalumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Leukocytosis	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Cardiac disorders
Sinus tachycardia	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Tachycardia	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Endocrine disorders
Hyperthyroidism	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Hypothyroidism	0/3 (0%)	0	1/3 (33.3%)	2	1/3 (33.3%)	1
Eye disorders
Vision blurred	0/3 (0%)	0	0/3 (0%)	0	2/3 (66.7%)	2
Gastrointestinal disorders
Abdominal distension	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0
Abdominal pain	0/3 (0%)	0	2/3 (66.7%)	2	1/3 (33.3%)	1
Abdominal pain lower	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Ascites	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Constipation	0/3 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0
Diarrhoea	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0
Gastrointestinal pain	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Nausea	0/3 (0%)	0	3/3 (100%)	4	0/3 (0%)	0
Vomiting	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0
General disorders
Chills	1/3 (33.3%)	2	1/3 (33.3%)	1	0/3 (0%)	0
Fatigue	0/3 (0%)	0	2/3 (66.7%)	2	1/3 (33.3%)	1
Injection site pain	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Injection site reaction	1/3 (33.3%)	1	1/3 (33.3%)	1	2/3 (66.7%)	2
Localised oedema	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Oedema peripheral	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	2
Pyrexia	1/3 (33.3%)	2	1/3 (33.3%)	2	0/3 (0%)	0
Infections and infestations
Bronchitis	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Tooth infection	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Urinary tract infection	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0
Investigations
Blood alkaline phosphatase increased	1/3 (33.3%)	2	1/3 (33.3%)	1	0/3 (0%)	0
Blood bilirubin increased	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0
Blood creatinine increased	2/3 (66.7%)	2	0/3 (0%)	0	0/3 (0%)	0
Weight decreased	0/3 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0
White blood cell count increased	2/3 (66.7%)	2	1/3 (33.3%)	1	0/3 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/3 (33.3%)	1	2/3 (66.7%)	2	1/3 (33.3%)	1
Dehydration	1/3 (33.3%)	1	1/3 (33.3%)	2	0/3 (0%)	0
Hypoalbuminaemia	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	2
Muscular weakness	0/3 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0
Nervous system disorders
Disturbance in attention	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Dizziness	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1
Tremor	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Psychiatric disorders
Anxiety	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Confusional state	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Insomnia	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1
Renal and urinary disorders
Pollakiuria	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)	2	0/3 (0%)	0	0/3 (0%)	0
Dyspnoea	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Rash maculo-papular	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Vascular disorders
Flushing	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Hot flush	1/3 (33.3%)	2	0/3 (0%)	0	0/3 (0%)	0
Hypertension	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0

Limitations/Caveats

The study was terminated after the Phase 1a part was complete.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.