A Study of LY3435151 in Participants With Solid Tumors

NCT04099277 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 17364J1Q-MC-JZIA
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

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

Keywords

immunotherapy; CD226 agonist

Outcome Measures

Primary Outcomes (1)

• Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs)

  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.

  Baseline through Cycle 2 (21 Day Cycles)

Secondary Outcomes (7)

• 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)

• PK: Cmax of LY3435151 in Combination With Pembrolizumab

  Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles)

• 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)

• 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)

• 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)

Study Arms (4)

Part A: 10 milligrams (mg) LY3435151

EXPERIMENTAL

Participants received intravenous (IV) push or IV bolus infusion of 10 mg LY3435151.

Drug: LY3435151

Part B: LY3435151 + Pembrolizumab Dose Escalation

EXPERIMENTAL

Pembrolizumab was not administered as study was terminated before completion of Part A of the dose escalation period.

Drug: LY3435151; Drug: Pembrolizumab

Part C: LY3435151 Dose Expansion

EXPERIMENTAL

Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.

Drug: LY3435151

Part D: LY3435151 + Pembrolizumab Dose Expansion

EXPERIMENTAL

Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.

Drug: LY3435151; Drug: Pembrolizumab

Interventions

LY3435151 DRUG

Administered IV

Part A: 10 milligrams (mg) LY3435151; Part B: LY3435151 + Pembrolizumab Dose Escalation; Part C: LY3435151 Dose Expansion; Part D: LY3435151 + Pembrolizumab Dose Expansion

Pembrolizumab DRUG

Administered IV

Part B: LY3435151 + Pembrolizumab Dose Escalation; Part D: LY3435151 + Pembrolizumab Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan

Location

Related Links

• A Study of LY3435151 in Participants With Solid Tumors

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Uterine Cervical Neoplasms; Carcinoma, Hepatocellular; Histiocytoma, Malignant Fibrous; Leiomyosarcoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Neoplasms, Muscle Tissue

Limitations and Caveats

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: September 23, 2019
• Study Start: October 28, 2019
• Primary Completion: March 5, 2020
• Study Completion: March 5, 2020
• Last Updated: August 31, 2021
• Results First Posted: August 31, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); JP (1)