A Study of LY3405105 in Participants With Advanced Cancer

NCT ID: NCT03770494

Last Updated: 2025-11-04

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-31

Study Completion Date

2021-02-04

Brief Summary

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The main purpose of this study is to investigate the safety of LY3405105 in participants with advanced cancer. The study has two parts phase 1a and phase 1b. Participants will only enroll in one part.

Detailed Description

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Conditions

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Solid Tumor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LY3405105

This study was designed to be conducted in two phases:

Phase 1a: This is a dose-escalation phase with a starting dose of LY3405105 1 milligram (mg) once daily (Part A1) or 2 mg three times per week (Part A2) on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Each dose-level will be determined and will have participants enrolled to it based on dose-limiting toxicity rate observed at previous dose-level. Intermediate, alternate, or higher dose levels will be explored if deemed necessary.

Phase 1b: This is a dose-expansion phase designed to explore the anti-tumor activity of recommended LY3405105 dose and dosing schedule determined in phase 1a, in participants with multiple tumor types.

\[Phase 1b was planned but not initiated based on the sponsor's decision and limited efficacy observed in phase 1a\]

Group Type EXPERIMENTAL

LY3405105

Intervention Type DRUG

Administered orally.

Interventions

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LY3405105

Administered orally.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Phase 1 a:

* Have histological or cytological evidence of a diagnosis of a solid tumor cancer that is advanced and/or metastatic
* Have available archived tissue for exploratory biomarker analysis
* Have adequate organ function
* Have discontinued all previous treatments for cancer and recovered from their side effects
* Are able to swallow capsules/tablets

Phase 1 b:

* Cohort 1: Triple-negative breast cancer (TNBC).
* Cohort 2: Clear cell ovarian cancer, endometrioid ovarian cancer, or endometrioid endometrial carcinoma with a LOF mutation in one or more of the following genes: ARID1A, KMT2C (MLL3), KMT2D (MLL2), or KDM6A (UTX).
* Cohort 3: Soft tissue sarcoma or sarcomatoid/rhabdoid malignancy with loss of expression of INI1, BRG1, or BRM by immunohistochemistry or a LOF mutation in one or more of the following genes: ARID1A, SMARCA2, SMARCA4, or SMARCB1. Participants aged ≥ 12 years with a body weight of ≥ 40 kilogram (kg) are acceptable for Cohorts 3. Participants with synovial sarcoma and a confirmed SS18-SSX gene fusion are also eligible.
* Cohort 4: Epithelioid sarcoma with INI1 loss of expression by immunohistochemistry or SMARCB1 LOF mutation. Participants aged ≥ 12 years with a body weight of ≥ 40 kilogram (kg) are acceptable for Cohorts 4.
* Cohort 5: Bladder cancer with a LOF mutation in one or more of the following genes: ARID1A, KMT2C (MLL3), KMT2D (MLL2), or KDM6A (UTX).

Exclusion Criteria

* Have symptomatic central nervous system (CNS) malignancy or metastasis
* Have symptomatic human immunodeficiency virus (HIV), Hepatitis A, B, or C
* Have congestive heart failure
* Are breastfeeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Institut Curie

Paris, , France

Site Status

Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Madrid Norte Sanchinarro

Madrid, , Spain

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Cheng-Kung Uni. Hosp.

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Countries

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United States Canada France Spain Taiwan

References

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Garralda E, Schram AM, Bedard PL, Schwartz GK, Yuen E, McNeely SC, Ribeiro S, Cunningham J, Wang Y, Urunuela A, Xu X, LoRusso P. A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors. Oncologist. 2024 Jan 5;29(1):e131-e140. doi: 10.1093/oncolo/oyad215.

Reference Type DERIVED
PMID: 37531083 (View on PubMed)

Sava GP, Fan H, Coombes RC, Buluwela L, Ali S. CDK7 inhibitors as anticancer drugs. Cancer Metastasis Rev. 2020 Sep;39(3):805-823. doi: 10.1007/s10555-020-09885-8.

Reference Type DERIVED
PMID: 32385714 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://trials.lillytrialguide.com/en-US/trial/ISkx1UpFmMIUiQYaemQSE

A Study of LY3405105 in Participants With Advanced Cancer

Other Identifiers

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J1F-MC-JZFA

Identifier Type: OTHER

Identifier Source: secondary_id

2018-002668-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17125

Identifier Type: -

Identifier Source: org_study_id

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