A Study of LY3405105 in Participants With Advanced Cancer

NCT03770494 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: 17125J1F-MC-JZFA2018-002668-23
• Study Type: interventional
• Target: 54
• Locations: 5 countries
• Sites: 17

Brief Summary

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs)

  A DLT is a clinically significant adverse event that is possibly related to the study drug and fulfils any one of the following criteria using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.0: 1\) Nonhematologic Grade ≥3 toxicity, except nausea, constipation, diarrhoea, vomiting or electrolyte disturbance lasting for \<72 hours and can be controlled with treatment, fatigue/anorexia lasting for \<5 days, transient grade 3 elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), without evidence of other hepatic injury; 2) Total bilirubin \>2×upper limit of normal (ULN) with ALT/AST \>3×ULN in the absence of cholestasis (alkaline phosphatase \<2×ULN); 3) Grade 4 neutropenia \>5 days duration, Any febrile neutropenia, Grade 4 thrombocytopenia of any duration, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 3/4 anemia or any other significant toxicity deemed to be dose limiting by investigators.

  Cycle 1 (Up To 28 Days)

• Phase 1b: Objective Response Rate (ORR): Percentage of Participants With a Confirmed Complete Response (CR) or Partial Response (PR)

  ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.

  Baseline through Measured Progressive Disease (Estimated up to 6 Months)

Secondary Outcomes (10)

• Phase 1a (Part A1): Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY3405105

  Cycle 1 Day 1 (Predose, 1, 2, 4, 6, 8, 24 hours post-dose)

• Phase 1a (Part A1): PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC(Tau)] of LY3405105

  Cycle 1 Day 15 (Predose, 1, 2, 4, 6, 8, 24 hours post-dose)

• Phase 1a (Part A2): PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3405105

  Cycle 1 Day 1 (Predose, 1, 2, 4, 6, 8, 24, 48 hours post-dose)

• Phase 1a (Part A2): PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC(Tau)] of LY3405105

  Cycle 1 Day 15 (Predose, 1, 2, 4, 6, 8, 24, 48 hours post-dose)

• Phase 1a: Objective Response Rate (ORR): Percentage of Participants With a Confirmed Complete Response (CR) or Partial Response (PR)

  Baseline through Measured Progressive Disease (Up To 349 Days)

Study Arms (1)

LY3405105

EXPERIMENTAL

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

Drug: LY3405105

Interventions

LY3405105 DRUG

Administered orally.

LY3405105

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (17)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06511, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5TY 2M9, Canada

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Institut Curie

Paris, 75248, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Madrid Norte Sanchinarro

Madrid, 28050, Spain

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng-Kung Uni. Hosp.

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 37531083 DERIVED

• 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.

  PMID: 32385714 DERIVED

Related Links

• A Study of LY3405105 in Participants With Advanced Cancer

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: December 10, 2018
• Study Start: January 31, 2019
• Primary Completion: February 4, 2021
• Study Completion: February 4, 2021
• Last Updated: November 4, 2025
• Results First Posted: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); CA (1); US (7); ES (2); TW (4)