First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
- Conditions
- Breast CancerSolid Tumors, Adult
- Interventions
- Registration Number
- NCT05768139
- Lead Sponsor
- Eli Lilly and Company
- Brief 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 720
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation (Advanced Solid Tumors) STX-478 * Cohort A0: Advanced Solid tumors expressing PI3Kα mutations * Cohort A1: HR+ breast cancer expressing PI3Kα mutations Dose Expansion STX-478 * Cohort A1: HR+/HER2- breast cancer expressing PI3Ka mutations * Cohort A2: Gynecologic cancers * Cohort A3: Head and Neck Squamous Cell Carcinoma * Cohorts A4/A5: Other solid tumors not included in Cohorts A1, A2, or A3 expressing PI3Kα mutations * Cohort A6: Endometrial cancer Dose Selection/Expansion: Combination STX-478 + fulvestrant STX-478 Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations Dose Selection/Expansion: Combination STX-478 + fulvestrant Fulvestrant Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations Dose Selection/Expansion Combination STX-478 STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination Fulvestrant STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination Ribociclib STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination Palbociclib STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination Letrozole STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination Anastrozole STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination Exemestane STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations
- Primary Outcome Measures
Name Time Method Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) First 28 days of treatment Proportion of participants who experience at least 1 DLT during the first 28 days of treatment First 28 days of treatment Cmax of STX-478 12 months AUC(0-inf) of STX-478 12 months AUC(0-t) of STX-478 12 months AUC(0-τ) of STX-478 12 months Change from baseline in ctDNA levels 12 months Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin (HbA1c) 12 months Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose 12 months Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide 12 months Objective response rate (ORR) defined as the percentage of participants with partial response or complete response based on RECIST 1.1 12 months Incidence of TEAEs/SAEs ≥ grade 2 12 months Frequency of TEAEs according to CTCAE v5.0 criteria 12 months Change in ECOG performance status 12 months
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (59)
Centre Antoine-Lacassagne
🇫🇷Nice, France
Universitätsmedizin Mannheim
🇩🇪Mannheim, Germany
Instituto Oncologico Dr Rosell (IOR)
🇪🇸Barcelona, Spain
Hospital Universitari Sant Joan de Reus
🇪🇸Reus, Spain
Hospital Universitario Virgen Macarena
🇪🇸Seville, Spain
UCSF Medical Center at Mission Bay
🇺🇸San Francisco, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Florida Cancer Specialists ORLANDO/DDU
🇺🇸Lake Mary, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Scroll for more (49 remaining)Centre Antoine-Lacassagne🇫🇷Nice, FrancePhilippe FollanaPrincipal Investigator