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NCT Number: NCT05768139

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

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.

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Key information

Conditions

Breast Cancer Adnexal Diseases Breast Diseases Breast Neoplasms Carcinoma Carcinoma, Squamous Cell Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Hereditary Sensory and Autonomic Neuropathies Heredodegenerative Disorders, Nervous System Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuromuscular Diseases Ovarian Diseases Ovarian Neoplasms Peripheral Nervous System Diseases Polyneuropathies Skin Diseases Skin and Connective Tissue Diseases Solid Tumors, Adult Squamous Cell Carcinoma of Head and Neck Urogenital Diseases Urogenital Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Institut Jules Bordet, Anderlecht, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

STX-478

Drug

STX-478 is a mutant-selective PI3Kα inhibitor

Other names: LY4064809, Tersolisib

Fulvestrant

Drug

Fulvestrant

Other names: Faslodex

Ribociclib

Drug

Ribociclib

Other names: Kisqali

Palbociclib

Drug

Palbociclib

Other names: Ibrance

letrozole

Drug

Letrozole

Other names: Femara

Anastrozole

Drug

Anastrozole

Other names: Arimidex

Exemestane

Drug

Exemestane

Other names: Aromasin

Tamoxifen

Drug

Tamoxifen

Other names: Nolvadex, Soltamox

Abemaciclib

Drug

Abemaciclib

Other names: Verzenio

Imlunestrant

Drug

Imlunestrant

Other names: Inluriyo

metformin

Drug

Metformin

Primary outcomes

  1. Number of participants who experience at least 1 Dose Limiting Toxicity (DLT)

    Time frame: First 28 days of treatment

  2. Proportion of participants who experience at least 1 DLT during the first 28 days of treatment

    Time frame: First 28 days of treatment

  3. Objective response rate (ORR) defined as the percentage of participants with partial response or complete response based on RECIST 1.1

    Time frame: 12 months

  4. Incidence of TEAEs/SAEs ≥ grade 2

    Time frame: 12 months

  5. Frequency of TEAEs according to CTCAE v5.0 criteria

    Time frame: 12 months

Secondary outcomes

  1. Cmax of STX-478

    Time frame: 12 months

  2. AUC(0-inf) of STX-478

    Time frame: 12 months

  3. AUC(0-t) of STX-478

    Time frame: 12 months

  4. AUC(0-τ) of STX-478

    Time frame: 12 months

  5. Change from baseline in ctDNA levels

    Time frame: 12 months

  6. Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin (HbA1c)

    Time frame: 12 months

  7. Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose

    Time frame: 12 months

  8. Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide

    Time frame: 12 months

  9. Change in ECOG performance status

    Time frame: 12 months

  10. Disease Control Rate (DCR) per RECIST v1.1, measured as percentage of participants with Complete Response

    Time frame: 12 months

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

Acronym: PIKALO-1

Important dates

Study start
2023
Primary completion
2030
Study completion
2030
First posted
Mar 14, 2023
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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