Clinical trial NCT06561685: A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors
Official title: An Open-label, Multicenter Study of LY4050784, a Selective SMARCA2/BRM Inhibitor, in Advanced Solid Tumor Malignancies With SMARCA4/BRG1 Alterations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Solid Tumor
Advanced Solid Tumor
Non-small Cell Lung Cancer
SMARCA4-Deficient Tumor
Keywords: SMARCA2
SMARCA4
Lung cancer
BRM
BRG1
Adenocarcinoma
Squamous cell carcinoma
Targeted therapy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-08-20
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Have one of the following locally advanced or metastatic solid tumor malignancy with SMARCA4 (BRG1) alteration:

  * Phase 1a dose escalation: Presence of any alteration in SMARCA4 (BRG1)
  * Phase 1b expansion: Part A: Non-small Cell Lung Cancer (NSCLC) that is locally advanced and not suitable for definitive locoregional therapy, or metastatic with presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
  * Phase 1b expansion: Part B: Any tumor type (other than NSCLC) that has the presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
  * Phase 1b expansion: Part C: Non-small Cell Lung Cancer (NSCLC) that is locally advanced and not suitable for definitive locoregional therapy, or metastatic with presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
* Prior Systemic Therapy Criteria:

  * Phase 1a dose escalation and Phase 1b (Part B): Participants who received all standard therapies for which the individual was deemed to be an appropriate candidate by the treating Investigator; or the individual is refusing the remaining most appropriate standard of care treatment; or there is no standard therapy available for the disease.
  * Phase 1b expansion (Part A): Participants must have received at least one line of therapy for advanced or metastatic disease.
  * Phase 1b expansion (Part C): Participants may be treatment naïve or have received therapy for advanced or metastatic disease
* Measurability of disease

  * Phase 1a dose escalation (excluding backfill): measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
  * Phase 1a backfill and Phase 1b expansion: Measurable disease required as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Exclusion Criteria:

* Participants with known or likely loss of function alteration of SMARCA2 (BRM) or malignancy with known association with SMARCA2 (BRM) alterations
* Prior exposure to SMARCA2 (BRM) inhibitor(s) and/or degrader(s) (prior exposure may be permitted for dose escalation)
* Participants with known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement
* Participants with history of increased risk of prolonged QT or significant arrythmia
* Significant cardiovascular disease
* Participants with active and/or treated for an additional primary malignancy within 2 years prior to enrolment
* Participants who are pregnant, breastfeeding or plan to breastfeed or expecting to conceive or father children during study or within 6 months after the last dose of study intervention
* Participants with history of active autoimmune diseases, history of allogenic stem cell/organ transplant or compromised immune system within past 2 years (Part C only)

Primary outcomes:
measure: Phase Ia: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs), and Adverse Event(s) (AEs)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: Phase 1a: To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of LY4050784
timeFrame: Up to Approximately 48 Months or 4 Years
measure: Phase 1b: To assess the antitumor activity of LY4050784 Monotherapy: Overall response rate (ORR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: Phase 1b (Dose optimization only): To confirm the RP2D/optimal dose based on safety and efficacy of LY4050784
timeFrame: Up to Approximately 48 Months or 4 Years
measure: Phase 1b (Combination cohorts/Part C): To assess the safety and tolerability of LY4050784 when administered in combination with other anticancer agents
timeFrame: Up to Approximately 48 Months or 4 Years
Secondary outcomes:
measure: To characterize the pharmacokinetics (PK) properties of LY4050784: Maximum Concentration (Cmax)
timeFrame: Cycle 1 (Day 8)
measure: To characterize the PK properties of LY4050784: Time to Maximum Concentration (Tmax)
timeFrame: Cycle 1 (Day 8)
measure: To characterize the PK properties of LY4050784: Area under the concentration versus time curve (AUC)
timeFrame: Cycle 1 (Day 8)
measure: Phase Ia: To evaluate the preliminary antitumor activity of LY4050784: Overall response rate (ORR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4050784: Duration of response (DOR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4050784: Time to response (TTR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4050784: Disease control rate (DCR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4050784: Progression free survival (PFS)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the PK properties of LY4050784 in combination cohorts: Maximum Concentration (Cmax) PK: Cmax of LY4050784
timeFrame: Cycle 1 (Day 8)
measure: To evaluate the PK properties of LY4050784 in combination cohorts: Time to Maximum Concentration (Tmax) PK: Tmax of LY4050784
timeFrame: Cycle 1 (Day 8)
measure: To evaluate the PK properties of LY4050784 in combination cohorts: Area under the concentration versus time curve (AUC)
timeFrame: Cycle 1 (Day 8)
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA
state: California
city: Aurora
country: United States
facility: University of Colorado Health Hospital
state: Colorado
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthOne
state: Colorado
city: Lake Mary
country: United States
facility: Florida Cancer Specialists ORLANDO/DDU
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: The University of Illinois at Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
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: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: USO-Virginia Cancer Specialists, PC
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Nagaizumi-cho,Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto City
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-Call 1-87) or 1-317-615-4559 Cal Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: