A Study of LY3435151 in Participants With Solid Tumors

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04099277
• Collaborator: (none)
• Enrollment: 2
• Locations: 2
• Arms: 4
• Actual Duration (Months): 4.2
• Patient Per Site: 1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The reason for this study is to see if the study drug LY3435151 is safe in participants with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor; Triple-negative Breast Cancer; Gastric Adenocarcinoma; Head and Neck Squamous Cell Carcinoma; Cervical Carcinoma; High Grade Serous Ovarian Carcinoma; Hepatocellular Carcinoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma	Drug: LY3435151; Drug: Pembrolizumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1a/1b Study of LY3435151 Administered to Patients With Advanced Solid Tumors
• Actual Study Start Date: Oct 28, 2019
• Actual Primary Completion Date: Mar 5, 2020
• Actual Study Completion Date: Mar 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: 10 milligrams (mg) LY3435151 Participants received intravenous (IV) push or IV bolus infusion of 10 mg LY3435151.	Drug: LY3435151; Administered IV
Experimental: Part B: LY3435151 + Pembrolizumab Dose Escalation Pembrolizumab was not administered as study was terminated before completion of Part A of the dose escalation period.	Drug: LY3435151; Administered IV; Drug: Pembrolizumab; Administered IV
Experimental: Part C: LY3435151 Dose Expansion Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.	Drug: LY3435151; Administered IV
Experimental: Part D: LY3435151 + Pembrolizumab Dose Expansion Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.	Drug: LY3435151; Administered IV; Drug: Pembrolizumab; Administered IV

Outcome Measures

Primary Outcome Measures

1. Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs) [Baseline through Cycle 2 (21 Day Cycles)]

   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: Any death not clearly due to the underlying disease or extraneous causes Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity Grade ≥4 neutropenia or thrombocytopenia >7 days Grade ≥3 thrombocytopenia with bleeding Grade ≥3 nausea/vomiting or diarrhea>72 hours with adequate antiemetic and other supportive care Grade ≥3 fatigue ≥1 week 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 Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151 [Cycle 1 Day 1 (C1D1) (Predose, 1, 3 hour (hr), C1D2 (24 hr), C1D4 (72hr), C1D8 (168hr), C1D15 (336hr)]

   Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151.

2. PK: Cmax of LY3435151 in Combination With Pembrolizumab [Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles)]

   PK: Cmax of LY3435151 in Combination with Pembrolizumab.

3. Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Baseline through Disease Progression or Death (Up to 4 Months)]

   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.

4. Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease [Baseline through Measured Progressive Disease (Up to 4 Months)]

   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.

5. Duration of Response (DoR) [Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 4 Months)]

   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.

6. Time to Response (TTR) [Baseline to Date of CR or PR (Up to 4 Months)]

   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.

7. Progression Free Survival (PFS) [Baseline to Objective Progression or Death Due to Any Cause (Up to 4 Months)]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participant must have certain types of cancer, which your study doctor will discuss with you

• Participant must have stopped other forms of treatment for cancer, which your study doctor will discuss with you

• Participant must be able and willing to provide a sample of your tumor before beginning treatment and once while on treatment. For certain tumor types, the outcome of the biopsy may exclude you from the study treatment (for Phase 1b)

• Participant must agree to use birth control

• Participant must have progressed through or are intolerant to therapies with known clinical benefit, which your study doctor will discuss with you

Exclusion Criteria:

• Participant must not have a history of tuberculosis, uncontrolled HIV or uncontrolled hepatitis B or C virus infection

• Participant must not have an autoimmune disease, which your study doctor will discuss with you

• Participant must not use corticosteroids, which your study doctor will discuss with you

• Participant must not have heart disease, Crohn's disease or brain cancer

• Participant must not be pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
2	National Cancer Center Hospital	Chuo-Ku	Tokyo	Japan	104-0045

Sponsors and Collaborators

• Eli Lilly and Company

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 - Jan 28, 2020
• Statistical Analysis Plan - Oct 4, 2019

More Information

Additional Information:

• A Study of LY3435151 in Participants With Solid Tumors

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04099277
• Other Study ID Numbers: 17364; J1Q-MC-JZIA
• First Posted: Sep 23, 2019
• Last Update Posted: Aug 31, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: immunotherapy; CD226 agonist
• Additional relevant MeSH terms: Carcinoma; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Leiomyosarcoma; Histiocytoma, Malignant Fibrous; Pembrolizumab

Study Results

Participant Flow

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 milligrams (mg) dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Period Title: Overall Study
STARTED	2
Received at Least 1 Dose of Study Drug	2
COMPLETED	0
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 50%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	1 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 50%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 50%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	1 50%
Japan	1 50%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs)
Description	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: Any death not clearly due to the underlying disease or extraneous causes Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity Grade ≥4 neutropenia or thrombocytopenia >7 days Grade ≥3 thrombocytopenia with bleeding Grade ≥3 nausea/vomiting or diarrhea>72 hours with adequate antiemetic and other supportive care Grade ≥3 fatigue ≥1 week 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 Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.
Time Frame	Baseline through Cycle 2 (21 Day Cycles)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. This outcome was not determined because the study terminated before completion of Part A of the dose escalation period.

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Measure Participants	0

2. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151
Description	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151.
Time Frame	Cycle 1 Day 1 (C1D1) (Predose, 1, 3 hour (hr), C1D2 (24 hr), C1D4 (72hr), C1D8 (168hr), C1D15 (336hr)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Measure Participants	2
Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter (µg/mL)]	NA (NA)

3. Secondary Outcome

Title	PK: Cmax of LY3435151 in Combination With Pembrolizumab
Description	PK: Cmax of LY3435151 in Combination with Pembrolizumab.
Time Frame	Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. The study was terminated early and no data was collected.

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Measure Participants	0

4. Secondary Outcome

Title	Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)
Description	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.
Time Frame	Baseline through Disease Progression or Death (Up to 4 Months)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. The study was terminated early and no data was collected.

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Measure Participants	0

5. Secondary Outcome

Title	Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease
Description	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.
Time Frame	Baseline through Measured Progressive Disease (Up to 4 Months)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. The study was terminated early and no data was collected.

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Measure Participants	0

6. Secondary Outcome

Title	Duration of Response (DoR)
Description	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.
Time Frame	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 4 Months)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. The study was terminated early and no data was collected.

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Measure Participants	0

7. Secondary Outcome

Title	Time to Response (TTR)
Description	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.
Time Frame	Baseline to Date of CR or PR (Up to 4 Months)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. The study was terminated early and no data was collected.

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Measure Participants	0

8. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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.
Time Frame	Baseline to Objective Progression or Death Due to Any Cause (Up to 4 Months)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. The study was terminated early and no data was collected.

Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
Measure Participants	0

Adverse Events

Time Frame	Up to 4 Months
Adverse Event Reporting Description	All randomized participants.
Arm/Group Title	10 mg LY3435151
Arm/Group Description	Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.
All Cause Mortality
	10 mg LY3435151
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	10 mg LY3435151
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Metabolism and nutrition disorders
Dehydration	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	10 mg LY3435151
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
Vomiting	1/2 (50%)	2
Injury, poisoning and procedural complications
Thoracic vertebral fracture	1/2 (50%)	1
Investigations
Electrocardiogram qt prolonged	1/2 (50%)	1
Troponin i increased	1/2 (50%)	1
Metabolism and nutrition disorders
Hyperkalaemia	1/2 (50%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/2 (50%)	1
Nervous system disorders
Dizziness	1/2 (50%)	1
Psychiatric disorders
Anxiety	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/2 (50%)	1
Vascular disorders
Orthostatic hypotension	1/2 (50%)	1

Limitations/Caveats

This study was terminated before completion of the dose escalation phase (Part A), due to strategic business decision made by the company.

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.