First-In-Human Study of STX-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations

Phase 1

Recruiting

• Conditions: EGFR/HER2 Exon 20 Insertion Mutation; Non-Small Cell Lung Cancer; NSCLC
• Interventions: Drug: STX-721 (RP2D); Drug: STX-721 (Escalated); Drug: STX-721 (3 dose levels)

• Registration Number: NCT06043817
• Lead Sponsor: Antares Therapeutics, Inc

Brief Summary

Study STX-721-101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721 in participants with non-small cell lung cancer (NSCLC) carrying EGFR/HER2 exon 20 insertion (ex20ins) mutations.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-01
• Study First Submitted QC: 2023-09-18
• Study First Posted: 2023-09-21
• Study Start: 2023-09-26
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-18
• Last Update Posted: 2025-04-23
• Primary Completion: 2027-06-01
• Study Completion: 2028-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 185

Inclusion Criteria

1. Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IV not eligible for curative intent surgery or chemoradiation
2. Part 1: Tumor tissue EGFR or HER2 exon 20 insertion mutations confirmed by qualified local laboratories. Parts 2 and 3: EGFR exon 20 insertion mutations confirmed by qualified local laboratories
3. Part 1: Has received all approved therapies for advanced or metastatic NSCLC or is ineligible. Part 2 and Part 3: Has received at least 1, but not more than 2, prior lines of treatment for advanced or metastatic NSCLC, 1 of which must be platinum-based chemotherapy unless contraindicated
4. Has documented tumor progression (based on radiological imaging)
5. Has new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen collected in the past 10 years available for genomic profiling
6. Has at least one measurable tumor lesion per RECIST v1.1
7. Is ≥18 years of age at the time of signing the ICF
8. Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Key

Exclusion Criteria

1. Has a tumor that is known to harbor EGFR ex20ins p.H773_V774insH variant, or any EGFR kinase domain activating mutation concurrent with either a T790M and/or C797S resistance mutations
2. Has history (within ≤2 years before screening) of solid tumor or hematological malignancy that is histologically distinct from NSCLC
3. Has symptomatic brain or spinal metastases
4. Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, except for alopecia and peripheral neuropathy
5. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., could compromise the participant's well-being) or would prevent, limit, or confound the protocol-specified assessments

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 3: Dose Expansion	STX-721 (RP2D)	-
Part 1: Dose Escalation	STX-721 (Escalated)	-
Part 2: RP2D Selection	STX-721 (3 dose levels)	-

Primary Outcome Measures

Name	Time	Method
Part 1 Dose Escalation (OBD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment	28 days
Part 2 RP2D Selection: C(max) of STX-721	1 year
Part 2 RP2D Selection: AUC(0-inf) of STX-721	1 year
Part 2 RP2D Selection: AUC(0-t) of STX-721	1 year
Part 2 RP2D Selection: AUC(0-τ) of STX-721	1 year
Part 2 RP2D Selection: Number of participants with confirmed objective response rate (ORR) defined as the percentage of participants with partial response (PR) or complete response (CR) based on RECIST v1.1 per investigator assessment.	1 year
Part 3 Dose Expansion: Number of participants with confirmed ORR defined as the percentage of participants with PR or complete response CR based on RECIST v1.1 per investigator assessment.	1 year
Part 1 Dose Escalation (MTD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment	28 days

Trial Locations

Locations (18)

Institut Claudius Regaud - PPDS; 🇫🇷 Toulouse, France

Gustave Roussy; 🇫🇷 Villejuif, France

EDOG Institut de Cancerologie de l'Ouest - PPDS; 🇫🇷 Saint-Herblain, Loire-Atlantique, France

Hospital Regional Universitario de Malaga - Hospital General; 🇪🇸 Málaga, Malaga, Spain

City of Hope; 🇺🇸 Irvine, California, United States

Levine Cancer Institute - Charlotte; 🇺🇸 Charlotte, North Carolina, United States

Thomas Jefferson University Research Facility; 🇺🇸 Philadelphia, Pennsylvania, United States

SCRI Oncology Partners - PPDS; 🇺🇸 Nashville, Tennessee, United States

University of Utah - Huntsman Cancer Institute - PPDS; 🇺🇸 Salt Lake City, Utah, United States

NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States

Charité - Universitätsmedizin Berlin (CBF) - Hindenburgdamm 30; 🇩🇪 Berlin, Germany

Chungbuk National University Hospital; 🇰🇷 Cheongju-si, Korea, Republic of

Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis; 🇳🇱 Amsterdam, Netherlands

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON; 🇪🇸 Barcelona, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan