Breast Cancer, Solid Tumors, Adult
Conditions
Keywords
Breast Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, HER2-negative breast cancer, HR-positive breast cancer, Gynecologic cancer, Endometrial cancer, Ovarian cancer, Cervical cancer, Head and neck cancer, Head and neck squamous cell carcinoma, Fulvestrant, Antineoplastic Agents, PI3Kα, PI3K alpha, PI3Kα mutation, Alpelisib, STX-478, PI3Kα inhibitor, Estrogen Receptor Antagonists, Estrogen Antagonists, Hormone Receptor Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Palbociclib, Ribociclib, PIK3CA, PIK3CA mutation, Aromatase inhibitor, Letrozole, Anastrozole, Exemestane, Imlunestrant, Inavolisib, Capivasertib, Abemaciclib
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, 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.
Interventions
DRUGSTX-478
STX-478 is a mutant-selective PI3Kα inhibitor
DRUGFulvestrant
Fulvestrant
DRUGRibociclib
Ribociclib
DRUGPalbociclib
Palbociclib
DRUGLetrozole
Letrozole
DRUGAnastrozole
Anastrozole
DRUGExemestane
Exemestane
DRUGTamoxifen
Tamoxifen
DRUGAbemaciclib
Abemaciclib
DRUGImlunestrant
Imlunestrant
DRUGMetformin
Metformin
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Change in ECOG performance status | 12 months |
| Disease Control Rate (DCR) per RECIST v1.1, measured as percentage of participants with Complete Response | 12 months |
Countries
Belgium, France, Germany, Ireland, Italy, Japan, Netherlands, Spain, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed