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

NCT05768139
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
880
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Lead sponsor
Eli Lilly and Company
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Start date
2023-04-17
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Number of sites
65
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Summary
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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Acronym
PIKALO-1
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Short title
First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
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Official 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
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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/Phase 2
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Study type
Interventional
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Completion date
2030-07-01
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First posted
2023-03-14
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Registry last updated
2026-07-07
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Primary completion date
2030-07-01
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Start date
2023-04-17
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Participants
880
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Participant count basis
Estimated
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Planned participants
880
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Protocol amendments
9
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Number of sites
65
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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
NCT05768139
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ClinicalTrials.gov ID
NCT05768139
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Masking description
In Part 1, Part 2 B0, B2, and B3, and Part 3 C0, D0, E0, F and A8, participants are assigned to intervention. In Part 2 B1 and Part 3 C1, D1, and E1, participants are randomized to doses
Sources for study design
clinicaltrials.gov

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

    Timeframe: First 28 days of treatment

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

    Timeframe: 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

    Timeframe: 12 months

  4. Incidence of TEAEs/SAEs ≥ grade 2

    Timeframe: 12 months

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

    Timeframe: 12 months

  1. Cmax of STX-478

    Timeframe: 12 months

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

    Timeframe: 12 months

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

    Timeframe: 12 months

  4. AUC(0-τ) of STX-478

    Timeframe: 12 months

  5. Change from baseline in ctDNA levels

    Timeframe: 12 months

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

    Timeframe: 12 months

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

    Timeframe: 12 months

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

    Timeframe: 12 months

  9. Change in ECOG performance status

    Timeframe: 12 months

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

    Timeframe: 12 months

Sources for outcomes
clinicaltrials.gov

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

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
Sources for eligibility
clinicaltrials.gov

  • Ellison Clinic at Saint John'sLos Angeles, United StatesRecruiting
  • UCSF Medical Center at Mission BaySan Francisco, United StatesRecruiting
  • University of Colorado Cancer CenterAurora, United StatesRecruiting
  • Yale-New Haven HospitalNew Haven, United StatesCompleted
  • Florida Cancer Specialists ORLANDO/DDULake Mary, United StatesCompleted
  • Moffitt Cancer CenterTampa, United StatesRecruiting
  • Winship Cancer Institute, Emory UniversityAtlanta, United StatesRecruiting
  • University of IowaIowa City, United StatesRecruiting
  • Louisiana State University Health Sciences CenterNew Orleans, United StatesRecruiting
  • Massachusetts General HospitalBoston, United StatesRecruiting
  • Dana-Farber Cancer InstituteBoston, United StatesRecruiting
  • Barbara Ann Karmanos Cancer InstituteDetroit, United StatesTerminated
  • START MidwestGrand Rapids, United StatesRecruiting
  • Saint Luke's Cancer InstituteKansas City, United StatesRecruiting
  • Washington UniversitySt Louis, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • UH Cleveland Medical CenterCleveland, United StatesRecruiting
  • Stefanie Spielman Comprehensive Breast CenterColumbus, United StatesRecruiting
  • Providence Cancer Institute Franz ClinicPortland, United StatesRecruiting
  • The West Clinic, PLLC dba West Cancer CenterGermantown, United StatesRecruiting
  • Sarah Cannon Research InstituteNashville, United StatesRecruiting
  • Mary Crowley Cancer Research CenterDallas, United StatesCompleted
  • Texas Oncology-Baylor Charles A. Sammons Cancer CenterDallas, United StatesRecruiting
  • University of Texas SouthwesternDallas, United StatesRecruiting
  • University of Texas MD Anderson Cancer CenterHouston, United StatesRecruiting

And 40 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-504807-94-00
  • 2023-000442-41
  • J6M-OX-JSGA
  • STX-478-101
Sources for references
clinicaltrials.gov

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