Clinical trial NCT05768139: First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Solid Tumors, Adult
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
Lead sponsor: Scorpion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-14
Enrollment: 720
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 (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.


Eligibility criteria: Key Inclusion Criteria:

1. Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
2. Has a new or recent tumor biopsy (collected at screening, if feasible) or will provide an adequate tissue sample prior to screening
3. Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types)
4. Is ≥18 years of age at the time of signing the ICF
5. Has an ECOG performance status score of 0 or 1 at screening
6. Has adequate organ function as defined per protocol

Key Exclusion Criteria:

1. Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
2. Has symptomatic brain or spinal metastases
3. 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).
4. Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
5. 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.
6. 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.
7. Has had radiotherapy within 14 days before the initiation of study treatment

Primary outcomes:
measure: Number of participants who experience at least 1 Dose Limiting Toxicity (DLT)
timeFrame: First 28 days of treatment
measure: Proportion of participants who experience at least 1 DLT during the first 28 days of treatment
timeFrame: First 28 days of treatment
measure: Cmax of STX-478
timeFrame: 12 months
measure: AUC(0-inf) of STX-478
timeFrame: 12 months
measure: AUC(0-t) of STX-478
timeFrame: 12 months
measure: AUC(0-τ) of STX-478
timeFrame: 12 months
measure: Change from baseline in ctDNA levels
timeFrame: 12 months
measure: Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin (HbA1c)
timeFrame: 12 months
measure: Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose
timeFrame: 12 months
measure: Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide
timeFrame: 12 months
measure: Objective response rate (ORR) defined as the percentage of participants with partial response or complete response based on RECIST 1.1
timeFrame: 12 months
measure: Incidence of TEAEs/SAEs ≥ grade 2
timeFrame: 12 months
measure: Frequency of TEAEs according to CTCAE v5.0 criteria
timeFrame: 12 months
measure: Change in ECOG performance status
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Angeles Clinic and Research Institute
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Center
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Lake Mary
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: START - Midwest
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Stefanie Spielman Comprehensive Breast Cancer
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: START - San Antonio
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Bordeaux
country: France
facility: Institut Bergonie City: Bordeaux
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli-Rome
state: Lazio
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Lombardia
city: Pozuelo De Alarcón
country: Spain
facility: NEXT Oncology - Hospital Quironsalud Madrid
state: Madrid
city: Barcelona
country: Spain
facility: START Barcelona_HM Nou Delfos
city: Barcelona
country: Spain
facility: Instituto de Investigacion Oncologica Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: START Madrid_Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: START Madrid_Hospital Universitario HM Sanchinarro
Study officials:
References: