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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

ConditionsBreast CancerSolid Tumors, Adult
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorEli Lilly and Company

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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

Treatment groups

880 Participants
are divided into 5 treatment groups
Group A: Dose Escalation (Advanced Solid Tumors)Experimental treatment 1 intervention
Group B: Dose ExpansionExperimental treatment 1 intervention
Group C: Dose Selection/Expansion: Combination STX-478 + fulvestrantExperimental treatment 2 interventions
Group D: Dose Selection/Expansion CombinationExperimental treatment 10 interventions
Group E: Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]Experimental treatment 9 interventions

Trial outcomes

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

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Eli Lilly and Company

Lead sponsor

Source ClinicalTrials.gov
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