First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05768139
• Other study ID #: STX-478-101
• Secondary ID: 2023-000442-4120
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 17, 2023
• Est. completion date: February 28, 2029

Study information

• Verified date: April 2024
• Source: Scorpion Therapeutics, Inc.
• Contact: For questions concerning enrollment
• Phone: Please email:
• Email: clinicaltrials[@]scorpiontx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: February 28, 2029
• Est. primary completion date: February 28, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 archival tumor specimen within 10 years prior to screening

3. Has a tumor that harbors a documented PI3Ka 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.

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

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 a tumor with inactivating mutations/deletions in PTEN, activating mutations in AKT (E17K), or a RAS mutation, RAF mutation, or other mutation(s) expected to confer resistance to PI3Ka inhibition, reported by and/or confirmed by a CLIA-certified or similarly certified laboratory; used in a single hospital or institution in EU only

4. 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

5. Cohorts A0, A1, A2, A3, A4, A5 and B: Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances

6. 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

7. 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

8. Has had radiotherapy within 14 days before the initiation of study treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Gynecologic Cancer
• HNSCC
• Solid Tumors, Adult

Intervention

Drug:
• STX-478
STX-478 is a second generation, mutant-selective, oral PI3Ka small molecule allosteric inhibitor.
• Fulvestrant
Fulvestrant will be administered according to local labeling.

Locations

Country	Name	City	State
Spain	Instituto de Investigacion Oncologica Vall d'Hebron	Barcelona
Spain	START Barcelona_HM Nou Delfos	Barcelona
Spain	Hospital Cli´nico San Carlos	Madrid
Spain	START Madrid_Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	START Madrid_Hospital Universitario HM Sanchinarro	Madrid
Spain	NEXT Oncology - Hospital Quironsalud Madrid	Pozuelo De Alarcón	Madrid
United States	University of Colorado Anschutz Medical Center	Aurora	Colorado
United States	Dana Farber Cancer Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Stefanie Spielman Comprehensive Breast Cancer	Columbus	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	NEXT Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Angeles Clinic and Research Institute	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	University of California, San Francisco	San Francisco	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Scorpion Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1.1 (Dose Escalation): Number of participants who experience at least 1 Dose Limiting Toxicity (DLT)		First 28 days of treatment
Primary	Part 1.1 (Dose Escalation): Proportion of participants who experience at least 1 DLT during the first 28 days of treatment.		First 28 days of treatment
Primary	Part 1.1 (Dose Escalation): Cmax of STX-478		12 months
Primary	Part 1.1 (Dose Escalation): AUC(0-inf) of STX-478		12 months
Primary	Part 1.1 (Dose Escalation): AUC(0-t) of STX-478		12 months
Primary	Part 1.1 (Dose Escalation): AUC(0-t) of STX-478		12 months
Primary	Part 1.1 (Dose Escalation): Change from baseline in ctDNA levels.		12 months
Primary	Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c]		12 months
Primary	Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose.		12 months
Primary	Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide.		12 months
Primary	Part 1.1 (Dose Escalation): Objective response rate (ORR).		12 months
Primary	Part 1.1 (Dose Escalation): Incidence of TEAEs/SAEs = grade 2.		12 months
Primary	Part 1.1 (Dose Escalation): Frequency of TEAEs according to CTCAE v5.0 criteria.		12 months
Primary	RP2D Selection (Parts 1.2-DS and 2.1): Cmax of STX-478		12 months
Primary	RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-inf) of STX-478		12 months
Primary	RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-t) of STX-478		12 months
Primary	RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-t) of STX-478		12 months
Primary	RP2D Selection (Parts 1.2-DS and 2.1): Change from baseline in ctDNA levels.		12 months
Primary	RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c]		12 months
Primary	RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose.		12 months
Primary	RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide		12 months
Primary	Parts 1.2-DS and 2.1 (RP2D Selection): ORR		12 months
Primary	Parts 1.2-DS and 2.1 (RP2D Selection): Frequency counts and percentages of AEs based on MedDRA and CTCAE v5.0		12 months
Primary	Parts 1.2-DS and 2.1 (RP2D Selection): Proportion of participants with DLTs.		12 months
Primary	Parts 1.2-DS and 2.1 (RP2D Selection): Change in ECOG performance status.		12 months
Primary	Parts 1.2-DE, 1.3, and 2.2 (Dose Expansion): ORR defined as the percentage of participants with partial response or complete response based on RECIST 1.1.		12 months