Trial Outcomes & Findings for A Study of LY3435151 in Participants With Solid Tumors (NCT NCT04099277)
NCT ID: NCT04099277
Last Updated: 2021-08-31
Results Overview
A DLT is defined as an Adverse Event that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0: 1. Any death not clearly due to the underlying disease or extraneous causes 2. Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity 3. Grade ≥4 neutropenia or thrombocytopenia \>7 days 4. Grade ≥3 thrombocytopenia with bleeding 5. Grade ≥3 nausea/vomiting or diarrhea\>72 hours with adequate antiemetic and other supportive care 6. Grade ≥3 fatigue ≥1 week 7. Grade ≥3 electrolyte abnormality that lasts\>72 hours, unless the Participant has clinical symptoms, in which case all Grade 3+electrolyte abnormality regardless of duration should count as a DLT 8. Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.
TERMINATED
PHASE1
2 participants
Baseline through Cycle 2 (21 Day Cycles)
2021-08-31
Participant Flow
Participant milestones
| Measure |
10 mg LY3435151
Participants received 10 milligrams (mg) dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
|
|---|---|
|
Overall Study
STARTED
|
2
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
2
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
10 mg LY3435151
Participants received 10 milligrams (mg) dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
|
|---|---|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Study of LY3435151 in Participants With Solid Tumors
Baseline characteristics by cohort
| Measure |
10 mg LY3435151
n=2 Participants
Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline through Cycle 2 (21 Day Cycles)Population: Zero participants were analyzed. This outcome was not determined because the study terminated before completion of Part A of the dose escalation period.
A DLT is defined as an Adverse Event that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0: 1. Any death not clearly due to the underlying disease or extraneous causes 2. Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity 3. Grade ≥4 neutropenia or thrombocytopenia \>7 days 4. Grade ≥3 thrombocytopenia with bleeding 5. Grade ≥3 nausea/vomiting or diarrhea\>72 hours with adequate antiemetic and other supportive care 6. Grade ≥3 fatigue ≥1 week 7. Grade ≥3 electrolyte abnormality that lasts\>72 hours, unless the Participant has clinical symptoms, in which case all Grade 3+electrolyte abnormality regardless of duration should count as a DLT 8. Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 1 Day 1 (C1D1) (Predose, 1, 3 hour (hr), C1D2 (24 hr), C1D4 (72hr), C1D8 (168hr), C1D15 (336hr)Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151.
Outcome measures
| Measure |
10 mg LY3435151
n=2 Participants
Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
|
|---|---|
|
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151
|
NA microgram per milliliter (µg/mL)
Geometric Coefficient of Variation NA
2.07, 7.16 (Individual values reported as there were only two participants)
|
SECONDARY outcome
Timeframe: Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles)Population: Zero participants were analyzed. The study was terminated early and no data was collected.
PK: Cmax of LY3435151 in Combination with Pembrolizumab.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline through Disease Progression or Death (Up to 4 Months)Population: Zero participants were analyzed. The study was terminated early and no data was collected.
Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline through Measured Progressive Disease (Up to 4 Months)Population: Zero participants were analyzed. The study was terminated early and no data was collected.
Disease Control Rate (DCR) is the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 4 Months)Population: Zero participants were analyzed. The study was terminated early and no data was collected.
DOR is the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Date of CR or PR (Up to 4 Months)Population: Zero participants were analyzed. The study was terminated early and no data was collected.
Time to response (TTR) is defined as the time from the date of start of treatment to the date measurement criteria for confirmed CR or PR (whichever is first recorded) are first met. For participants who are not known to have achieved CR or PR as of the data inclusion cut-off date, TTR will be censored at the date of the last objective disease assessment prior the date of any subsequent systematic anticancer therapy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Objective Progression or Death Due to Any Cause (Up to 4 Months)Population: Zero participants were analyzed. The study was terminated early and no data was collected.
PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Outcome measures
Outcome data not reported
Adverse Events
10 mg LY3435151
Serious adverse events
| Measure |
10 mg LY3435151
n=2 participants at risk
Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
|
|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
Other adverse events
| Measure |
10 mg LY3435151
n=2 participants at risk
Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
|
|---|---|
|
Gastrointestinal disorders
Vomiting
|
50.0%
1/2 • Number of events 2 • Up to 4 Months
All randomized participants.
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
|
Investigations
Electrocardiogram qt prolonged
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
|
Investigations
Troponin i increased
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
50.0%
1/2 • Number of events 2 • Up to 4 Months
All randomized participants.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
|
Nervous system disorders
Dizziness
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
|
Psychiatric disorders
Anxiety
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
|
Vascular disorders
Orthostatic hypotension
|
50.0%
1/2 • Number of events 1 • Up to 4 Months
All randomized participants.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60