First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
- Conditions
- Breast CancerGynecologic CancerHNSCCSolid Tumors, Adult
- Interventions
- Registration Number
- NCT05768139
- Lead Sponsor
- Scorpion Therapeutics, Inc.
- Brief Summary
Study STX-478-101 is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 in participants with advanced solid tumors with certain mutations.
Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors and breast cancer; Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with 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
- 400
- 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 archival tumor specimen within 10 years prior to screening
- Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types) obtained either from tumor or plasma samples, determined by PCR or NGS-based assay as an FDA-approved test in US, CE marked in EU, or obtained as part of normal clinical care in a CLIA certified or similarly certified laboratory.
- Is ≥18 years of age at the time of signing the ICF
- Has an ECOG performance status score of 0 or 1 at screening
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 a tumor with known mutations/deletions in PTEN and activating mutations in AKT (E17K) confirmed by a CLIA-certified or similarly certified laboratory
- Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2 (based on FPG and HbA1c thresholds defined in the inclusion criteria) requiring antihyperglycemic medication
- Cohorts A0, A1, A2, A3, A4, A5 and B: 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
- 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 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 + fulvestrant + CDK4/6 inhibitor STX-478 Cohort C/D: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination STX-478 + fulvestrant + CDK4/6 inhibitor Fulvestrant Cohort C/D: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination STX-478 + fulvestrant + CDK4/6 inhibitor Ribociclib Cohort C/D: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations Dose Selection/Expansion Combination STX-478 + fulvestrant + CDK4/6 inhibitor Palbociclib Cohort C/D: 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 (33)
START Barcelona_HM Nou Delfos
🇪🇸Barcelona, Spain
Instituto de Investigacion Oncologica Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Yale University
🇺🇸New Haven, Connecticut, United States
Florida Cancer Specialists & Research Institute
🇺🇸Lake Mary, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Center
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
START - Midwest
🇺🇸Grand Rapids, Michigan, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Stefanie Spielman Comprehensive Breast Cancer
🇺🇸Columbus, Ohio, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
START - San Antonio
🇺🇸San Antonio, Texas, United States
START Mountain Region
🇺🇸West Valley City, Utah, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States
Institut Bergonie City: Bordeaux
🇫🇷Bordeaux, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif, France
NEXT Oncology - Hospital Quironsalud Madrid
🇪🇸Pozuelo De Alarcón, Madrid, Spain
Fondazione Policlinico Universitario A Gemelli-Rome
🇮🇹Roma, Lazio, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Lombardia, Italy
START Madrid_Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Providence Cancer Institute
🇺🇸Portland, Oregon, United States
Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
University of Colorado Anschutz Medical Center
🇺🇸Aurora, Colorado, United States
START Madrid_Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain