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

NCT05768139

RecruitingPhase 1, Phase 2

Sponsor: Eli Lilly and Company

Conditions: Breast Cancer, Solid Tumors, Adult

Interventions: STX-478, Fulvestrant, Ribociclib, Palbociclib, Letrozole

Countries: United States, Belgium, France, Germany, Ireland, Italy, Japan, Netherlands

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.

Eligibility overview

Sex: ALL

Age: 18 Years to

Healthy volunteers: No

Study type: INTERVENTIONAL

Eligibility criteria
Key Inclusion Criteria:

* Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
* Has a new or recent tumor biopsy (collected at screening, if feasible) or will provide an adequate tissue sample prior to screening
* Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types)
* Is ≥18 years of age at the time of signing the ICF
* Has an ECOG performance status score of 0 or 1 at screening
* Has adequate organ function as defined per protocol

Key Exclusion Criteria:

* Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
* Has symptomatic brain or spinal metastases
* Has an established diagnosis of uncontrolled diabetes mellitus (defined as HbA1c ≥8% and/or FBG ≥140 mg/dL \[7.7 mmol/L\] and/or requiring or required insulin).
* Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
* Has had treatment with any local or systemic antineoplastic therapy or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, prior to the initiation of study treatment up to a maximum washout period of 28 days. Endocrine therapy does not require a washout period if the patient is enrolling in a cohort with the same combination endocrine therapy.
* Has toxicities from previous anticancer therapies that have not resolved to baseline levels or CTCAE grade ≤1, with the exception of alopecia and peripheral neuropathy.
* Has had radiotherapy within 14 days before the initiation of study treatment
Locations (65)
  • Los Angeles, California, United States
  • San Francisco, California, United States
  • Aurora, Colorado, United States
  • New Haven, Connecticut, United States
  • Lake Mary, Florida, United States
  • Tampa, Florida, United States
  • Atlanta, Georgia, United States
  • Iowa City, Iowa, United States
  • New Orleans, Louisiana, United States
  • Boston, Massachusetts, United States
  • Boston, Massachusetts, United States
  • Detroit, Michigan, United States
  • Grand Rapids, Michigan, United States
  • Kansas City, Missouri, United States
  • St Louis, Missouri, United States
  • New York, New York, United States
  • Cleveland, Ohio, United States
  • Columbus, Ohio, United States
  • Portland, Oregon, United States
  • Germantown, Tennessee, United States
  • Nashville, Tennessee, United States
  • Dallas, Texas, United States
  • Dallas, Texas, United States
  • Dallas, Texas, United States
  • Houston, Texas, United States
  • San Antonio, Texas, United States
  • West Valley City, Utah, United States
  • Fairfax, Virginia, United States
  • Anderlecht, Belgium
  • Leuven, Belgium
  • + 35 more on CT.gov