The main purpose of this study is to find out whether the study drug, LY4050784, is safe, tolerable and effective in participants alone or in combination with other anticancer agents. In addition, with locally advanced or metastatic solid tumors with a BRG1 (Brahma-related gene 1, also known as SMARCA4) alteration who have previously received, do not qualify for, or are refusing standard of care treatments, or there is no standard therapy available for the disease. The study is conducted in two parts - phase Ia (dose-escalation) and phase Ib (dose-optimization, dose-expansion). The study will last up to approximately 4 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
340
Oral
Administered IV.
Administered IV.
Administered IV.
Administered IV.
Administered IV.
Administered IV.
UCLA
Santa Monica, California, United States
RECRUITINGUniversity of Colorado Health Hospital
Aurora, Colorado, United States
RECRUITINGSarah Cannon Research Institute at HealthOne
Denver, Colorado, United States
RECRUITINGFlorida Cancer Specialists ORLANDO/DDU
Lake Mary, Florida, United States
Phase Ia: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs), and Adverse Event(s) (AEs)
A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module
Time frame: Up to Approximately 48 Months or 4 Years
Phase 1a: To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of LY4050784
Number of participants with dose-limiting toxicities (DLTs)
Time frame: Up to Approximately 48 Months or 4 Years
Phase 1b: To assess the antitumor activity of LY4050784 Monotherapy: Overall response rate (ORR)
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Time frame: Up to Approximately 48 Months or 4 Years
Phase 1b (Dose optimization only): To confirm the RP2D/optimal dose based on safety and efficacy of LY4050784
A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module, ORR and Duration of Response (DOR) per Investigator
Time frame: Up to Approximately 48 Months or 4 Years
Phase 1b (Combination cohorts/Part C): To assess the safety and tolerability of LY4050784 when administered in combination with other anticancer agents
A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module
Time frame: Up to Approximately 48 Months or 4 Years
To characterize the pharmacokinetics (PK) properties of LY4050784: Maximum Concentration (Cmax)
PK: Cmax of LY4050784
Time frame: Cycle 1 (Day 8)
To characterize the PK properties of LY4050784: Time to Maximum Concentration (Tmax)
PK: Tmax of LY4050784
Time frame: Cycle 1 (Day 8)
To characterize the PK properties of LY4050784: Area under the concentration versus time curve (AUC)
PK: AUC of LY4050784
Time frame: Cycle 1 (Day 8)
Phase Ia: To evaluate the preliminary antitumor activity of LY4050784: Overall response rate (ORR)
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Duration of response (DOR)
DOR per investigator assessed RECIST 1.1
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Time to response (TTR)
TTR per investigator assessed RECIST 1.1
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Disease control rate (DCR)
DCR per investigator assessed RECIST 1.1
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Progression free survival (PFS)
PFS per investigator assessed RECIST 1.1
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the PK properties of LY4050784 in combination cohorts: Maximum Concentration (Cmax) PK: Cmax of LY4050784
Time frame: Cycle 1 (Day 8)
To evaluate the PK properties of LY4050784 in combination cohorts: Time to Maximum Concentration (Tmax) PK: Tmax of LY4050784
Time frame: Cycle 1 (Day 8)
To evaluate the PK properties of LY4050784 in combination cohorts: Area under the concentration versus time curve (AUC)
Time frame: Cycle 1 (Day 8)
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACT
Physicians interested in becoming principal investigators please contact
CONTACT
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University of Miami
Miami, Florida, United States
RECRUITINGUniversity of Chicago
New Lenox, Illinois, United States
RECRUITINGMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGColumbia University Medical Center
New York, New York, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITING...and 21 more locations