First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

Conditions

• Breast Cancer
• Solid Tumors, Adult

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• STX-478 — DRUG
  STX-478 is a mutant-selective PI3Kα inhibitor
• Fulvestrant — DRUG
  Fulvestrant
• Ribociclib — DRUG
  Ribociclib
• Palbociclib — DRUG
  Palbociclib
• Letrozole — DRUG
  Letrozole
• Anastrozole — DRUG
  Anastrozole
• Exemestane — DRUG
  Exemestane
• Tamoxifen — DRUG
  Tamoxifen
• Abemaciclib — DRUG
  Abemaciclib
• Imlunestrant — DRUG
  Imlunestrant
• Metformin — DRUG
  Metformin

Study Details

Study STX-478-101 (LY4064809) is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 (LY4064809) in participants with advanced solid tumors with P13Ka mutations. Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors. Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with hormone receptor positive (HR+) breast cancer. Part 3 will evaluate STX-478 as combination therapy with endocrine therapy (aromatase inhibitors, fulvestrant, tamoxifen, or imlunestrant) and a CDK4/6 Inhibitor (either Ribociclib, Palbociclib or Abemaciclib) in participants with HR+ breast cancer. Each study part will include a 28-day screening period, followed by treatment with STX-478 monotherapy or combination therapy.

Key Dates

Start date

Apr 17, 2023

Status verified

Jun 2026

Primary completion

Jul 31, 2030

Completion

Jul 31, 2030

Study Design

Enrollment

880 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Dose Escalation (Advanced Solid Tumors)
  * Cohort A0: Advanced Solid tumors expressing PI3Kα mutations * Cohort A1: HR+ breast cancer expressing PI3Kα mutations
• Experimental: Dose Expansion
  * Cohort A2: Gynecologic cancers * Cohort A3: Head and Neck Squamous Cell Carcinoma * Cohorts A4/A5: Other solid tumors not included in Cohorts A1, A2, A3 expressing PI3Kα mutations * Cohort A6: Endometrial cancer * Cohort A7: Non-gastrointestinal solid tumors
• Experimental: Dose Selection/Expansion: Combination STX-478 + fulvestrant
  Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations
• Experimental: Dose Selection/Expansion Combination
  STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations
• Experimental: Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]
  CDK4/6 inhibitor therapy in Cohort A8: all solid tumors Cohort B2 and Cohort F: HR+/HER2- or HR+/HER2 low breast cancer expressing PI3Kα mutations

Primary Outcome Measure

Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) [ Time Frame: First 28 days of treatment ]

Central Contacts

• Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
  1-317-615-4559
  [email protected]
• Physicians interested in becoming principal investigators please contact
  [email protected]

Locations (28)

Find similar trials in Los Angeles, CA

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