A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors

NCT06561685
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
340
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Lead sponsor
Eli Lilly and Company
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Start date
2024-09-19
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Number of sites
33
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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.
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Short title
A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors
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Official title
An Open-label, Multicenter Study of LY4050784, a Selective SMARCA2/BRM Inhibitor, in Advanced Solid Tumor Malignancies With SMARCA4/BRG1 Alterations
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-10-01
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First posted
2024-08-20
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Registry last updated
2026-08-07
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Primary completion date
2027-10-01
clinicaltrials.gov
Start date
2024-09-19
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Participants
340
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Participant count basis
Estimated
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Planned participants
340
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Protocol amendments
3
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Number of sites
33
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Eli Lilly and Company
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06561685
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ClinicalTrials.gov ID
NCT06561685
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Registry record
Open registry record
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Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. 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

    A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module

  2. 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

    Number of participants with dose-limiting toxicities (DLTs)

  3. Phase 1b: To assess the antitumor activity of LY4050784 Monotherapy: Overall response rate (ORR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)

  4. 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

    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

  5. 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

    A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module

  1. To characterize the pharmacokinetics (PK) properties of LY4050784: Maximum Concentration (Cmax)

    Timeframe: Cycle 1 (Day 8)

    PK: Cmax of LY4050784

  2. To characterize the PK properties of LY4050784: Time to Maximum Concentration (Tmax)

    Timeframe: Cycle 1 (Day 8)

    PK: Tmax of LY4050784

  3. To characterize the PK properties of LY4050784: Area under the concentration versus time curve (AUC)

    Timeframe: Cycle 1 (Day 8)

    PK: AUC of LY4050784

  4. Phase Ia: To evaluate the preliminary antitumor activity of LY4050784: Overall response rate (ORR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)

  5. To evaluate the preliminary antitumor activity of LY4050784: Duration of response (DOR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    DOR per investigator assessed RECIST 1.1

  6. To evaluate the preliminary antitumor activity of LY4050784: Time to response (TTR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    TTR per investigator assessed RECIST 1.1

  7. To evaluate the preliminary antitumor activity of LY4050784: Disease control rate (DCR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    DCR per investigator assessed RECIST 1.1

  8. To evaluate the preliminary antitumor activity of LY4050784: Progression free survival (PFS)

    Timeframe: Up to Approximately 48 Months or 4 Years

    PFS per investigator assessed RECIST 1.1

  9. To evaluate the PK properties of LY4050784 in combination cohorts: Maximum Concentration (Cmax) PK: Cmax of LY4050784

    Timeframe: Cycle 1 (Day 8)

  10. To evaluate the PK properties of LY4050784 in combination cohorts: Time to Maximum Concentration (Tmax) PK: Tmax of LY4050784

    Timeframe: Cycle 1 (Day 8)

  11. To evaluate the PK properties of LY4050784 in combination cohorts: Area under the concentration versus time curve (AUC)

    Timeframe: Cycle 1 (Day 8)

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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)
Sources for eligibility
clinicaltrials.gov

  • UCLASanta Monica, United StatesRecruiting
  • University of Colorado Health HospitalAurora, United StatesRecruiting
  • Sarah Cannon Research Institute at HealthOneDenver, United StatesRecruiting
  • Florida Cancer Specialists ORLANDO/DDULake Mary, United StatesActive, not recruiting
  • University of MiamiMiami, United StatesRecruiting
  • University of ChicagoNew Lenox, United StatesRecruiting
  • Massachusetts General HospitalBoston, United StatesRecruiting
  • Dana-Farber Cancer InstituteBoston, United StatesRecruiting
  • Columbia University Medical CenterNew York, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • Ohio State University HospitalColumbus, United StatesRecruiting
  • Sarah Cannon Research InstituteNashville, United StatesRecruiting
  • SCRI Oncology PartnersNashville, United StatesRecruiting
  • Vanderbilt-Ingram Cancer CenterNashville, United StatesRecruiting
  • MD Anderson Cancer CenterHouston, United StatesRecruiting
  • USO-Virginia Cancer Specialists, PCFairfax, United StatesRecruiting
  • Medical College of WisconsinMilwaukee, United StatesRecruiting
  • Institut BergonieBordeaux, FranceNot yet recruiting
  • Institut CurieParis, FranceRecruiting
  • Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEPVillejuif, FranceRecruiting
  • Charite-Universitatsmedizin BerlinBerlin, GermanyRecruiting
  • Universitaetsklinikum EssenEssen, GermanyNot yet recruiting
  • Krankenhaus NordwestFrankfurt am Main, GermanyNot yet recruiting
  • National Cancer Center HospitalChūōku, JapanRecruiting
  • National Cancer Center Hospital EastKashiwa, JapanRecruiting

And 8 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • J5M-OX-JOXA
Sources for references
clinicaltrials.gov

Related records

Drugs (5)

Lead sponsors (1)

Conditions (4)

Targets (19)