Trial Outcomes & Findings for A Study of LY2510924 and Sunitinib in Patients With Metastatic Renal Cell Carcinoma (NCT NCT01391130)

Last Updated: 2019-07-23

Results Overview

PFS is defined as the time from date of study Randomization to the first date of objectively determined progressive disease(PD) or death from any cause defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0).PD was defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study(including the baseline sum if that is the smallest).In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions was also considered PD.For participants still alive at the time of analysis and without evidence of tumor progression,PFS would be censored at the date of the most recent objective progression-free observation.For participants who receive subsequent anticancer therapy prior to objective disease progression or death,PFS was censored at the date of the last objective progression-free observation prior to the date of subsequent therapy.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

110 participants

Primary outcome timeframe

Randomization to Measured Progressive Disease or Date of Death From Any Cause (Up to 67 Months)

Results posted on

2019-07-23

Participant Flow

Participants who died (any cause) or had disease progression at the time the primary analysis were considered to be study completers.

Participant milestones

Participant milestones
Measure	LY2510924 + Sunitinib LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Overall Study STARTED	73	37
Overall Study Received At Least One Dose of Study Drug	72	36
Overall Study COMPLETED	67	31
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Reasons for withdrawal
Measure	LY2510924 + Sunitinib LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Overall Study Withdrawal by Subject	3	2
Overall Study Physician Decision	2	3
Overall Study Did not Receive Drug	1	1

Baseline Characteristics

A Study of LY2510924 and Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY2510924 + Sunitinib n=72 Participants LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib n=36 Participants 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Total n=108 Participants Total of all reporting groups
Age, Continuous	64.51 years STANDARD_DEVIATION 11.332 • n=5 Participants	64.21 years STANDARD_DEVIATION 9.474 • n=7 Participants	64.41 years STANDARD_DEVIATION 10.705 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	12 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	24 Participants n=7 Participants	72 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	71 Participants n=5 Participants	34 Participants n=7 Participants	105 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	68 Participants n=5 Participants	34 Participants n=7 Participants	102 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	72 Participants n=5 Participants	36 Participants n=7 Participants	108 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to Measured Progressive Disease or Date of Death From Any Cause (Up to 67 Months)

Population: All participants who received at least one dose of study drug. Participants censored were LY2510924 + Sunitinib = 16 and Sunitinib=12.

Outcome measures

Outcome measures
Measure	LY2510924 + Sunitinib n=72 Participants LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib n=36 Participants 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Progression Free Survival (PFS)	8.08 Months Interval 5.52 to 10.64	12.25 Months Interval 2.66 to 20.01

SECONDARY outcome

Timeframe: Baseline to Date of Tumor Response or Measured Progressive Disease or Date of Death from any Cause ((Up to 67 Months)

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

ORR is defined as the number of participants with a best response of CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.

Outcome measures

Outcome measures
Measure	LY2510924 + Sunitinib n=72 Participants LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib n=36 Participants 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])	31.9 percentage of participants Interval 21.17 to 42.71	38.9 percentage of participants Interval 22.96 to 54.81

SECONDARY outcome

Timeframe: Randomization to Date of Death from Any Cause (Up to 67 Months)

Population: All participants who received at least one dose of study drug. Participants censored were LY2510924 + Sunitinib=19 and Sunitinib=10.

OS is defined as the time from the date of study randomization to the date of death from any cause. For participants who were still alive as of the data cut-off date, OS time will be censored on the date of the participant's last contact (last contact for participants in post-discontinuation = last known alive date in mortality status).

Outcome measures

Outcome measures
Measure	LY2510924 + Sunitinib n=72 Participants LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib n=36 Participants 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Overall Survival (OS)	24.18 months Interval 13.9 to 35.19	23.82 months Interval 11.6 to 43.86

SECONDARY outcome

Timeframe: Date of First Response to Date of Progressive Disease (Up to 67 Months)

Population: All participants who received at least one dose of study drug. Participants censored were LY2510924 + Sunitinib=7 and Sunitinib=7.

DOR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Outcome measures

Outcome measures
Measure	LY2510924 + Sunitinib n=72 Participants LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib n=36 Participants 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Duration of Overall Response (DOR)	11.30 Months Interval 5.36 to 16.99	12.42 Months Interval 3.15 to The data were not evaluable for the upper confidence interval.

SECONDARY outcome

Timeframe: Date of Complete Response to the Date of Progressive Disease (Up to 67 Months)

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

Duration of complete response is defined as the time from the date when the measurement criteria are met for complete response until the date of first observation of objective disease progression (taking as reference for PD the smallest measurements recorded since the treatment started). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Outcome measures

Outcome measures
Measure	LY2510924 + Sunitinib LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib n=1 Participants 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Duration of Complete Response	—	10 months Only one participant had CR.

Adverse Events

LY2510924 + Sunitinib

Serious events: 31 serious events

Other events: 70 other events

Deaths: 0 deaths

Sunitinib

Serious events: 10 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	LY2510924 + Sunitinib n=72 participants at risk LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Sunitinib n=36 participants at risk 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Idiopathic thrombocytopenic purpura	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Cardiac disorders Cardiac arrest	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure congestive	2.8% 2/72 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Cardiac disorders Pericardial effusion	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
General disorders Asthenia	2.8% 2/72 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
General disorders Disease progression	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
General disorders Fatigue	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
General disorders Pain	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
General disorders Pyrexia	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Hepatobiliary disorders Bile duct stone	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Infections and infestations Bacteraemia	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Infections and infestations Cellulitis	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Infections and infestations Clostridial infection	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Infections and infestations Pancreas infection	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Infections and infestations Peridiverticular abscess	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Infections and infestations Pneumonia	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Post procedural infection	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	1.4% 1/72 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	2.8% 2/72 • Number of events 3 All participants who received at least one dose of study drug.	5.6% 2/36 • Number of events 2 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Haemarthrosis	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intracranial tumour haemorrhage	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic renal cell carcinoma	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Brain oedema	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Nervous system disorders Central nervous system lesion	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Nervous system disorders Convulsion	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Nervous system disorders Syncope	2.8% 2/72 • Number of events 2 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 2 All participants who received at least one dose of study drug.
Psychiatric disorders Delirium	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Psychiatric disorders Mental status changes	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Renal and urinary disorders Cystitis haemorrhagic	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Renal and urinary disorders Haematuria	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure acute	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.2% 3/72 • Number of events 3 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Surgical and medical procedures Spinal operation	0.00% 0/72 All participants who received at least one dose of study drug.	2.8% 1/36 • Number of events 1 All participants who received at least one dose of study drug.
Vascular disorders Deep vein thrombosis	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.
Vascular disorders Embolism	1.4% 1/72 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/36 All participants who received at least one dose of study drug.