Clinical trial NCT06043817: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer
NSCLC
EGFR/HER2 Exon 20 Insertion Mutation
Lead sponsor: Antares Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 185
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-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.


Eligibility criteria: Key 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

Primary outcomes:
measure: Part 1 Dose Escalation (MTD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
timeFrame: 28 days
measure: Part 1 Dose Escalation (OBD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
timeFrame: 28 days
measure: Part 2 RP2D Selection: C(max) of STX-721
timeFrame: 1 year
measure: Part 2 RP2D Selection: AUC(0-inf) of STX-721
timeFrame: 1 year
measure: Part 2 RP2D Selection: AUC(0-t) of STX-721
timeFrame: 1 year
measure: Part 2 RP2D Selection: AUC(0-τ) of STX-721
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Huntington Beach
country: United States
facility: City of Hope
state: California
city: Irvine
country: United States
facility: City of Hope
state: California
city: Charlotte
country: United States
facility: Levine Cancer Institute - Charlotte
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University Research Facility
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners - PPDS
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Institute - PPDS
state: Utah
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Saint-Herblain
country: France
facility: EDOG Institut de Cancerologie de l'Ouest - PPDS
state: Loire-Atlantique
city: Toulouse
country: France
facility: Institut Claudius Regaud - PPDS
city: Villejuif
country: France
facility: Gustave Roussy
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin (CBF) - Hindenburgdamm 30
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital General
state: Malaga
city: Barcelona
country: Spain
facility: Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
References: