Clinical trial NCT03770494: A Study of LY3405105 in Participants With Advanced Cancer
Official title: A Phase 1a/1b Study of LY3405105 Administered to Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2018-12-10
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Baseline through Cycle 1 (28 Day Cycle)
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of LY3405105
timeFrame: Predose Lead in Day 1 through Predose Cycle 2 Day 1 (28 Day Cycles)
measure: Objective Response Rate (ORR): Percentage of Participants with a Confirmed Complete Response (CR) or Partial Response (PR)
timeFrame: Baseline through Measured Progressive Disease (Estimated up to 6 Months)
measure: Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), Confirmed CR or PR
timeFrame: Baseline through Measured Progressive Disease (Estimated up to 6 Months)
measure: Duration of Response (DOR)
timeFrame: Date of Confirmed CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)
measure: Time to Response (TTR)
timeFrame: Baseline to Date of Confirmed CR or PR (Estimated up to 6 Months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)
measure: Overall Survival (OS)
timeFrame: Baseline to Date of Death from Any Cause (Estimated up to 12 Months)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Bordeaux
country: France
facility: Institut Bergonie
city: Paris
country: France
facility: Institut Curie
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Madrid Norte Sanchinarro
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng-Kung Uni. Hosp.
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Eli Lilly and Company
name: 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
References:
citation: 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.