Trials Today

First-In-Human Study of STX-721/PFL-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR or HER2 Exon 20 Insertion Mutations

Purpose

Study STX-721-101/PFL-721CI101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721/PFL-721 in participants with non-small cell lung cancer (NSCLC) carrying EGFR or HER2 exon 20 insertion (ex20ins) mutations.

Conditions

Non-Small Cell Lung Cancer
NSCLC
EGFR/HER2 Exon 20 Insertion Mutation

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

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/HER2 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 approved 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

Exclusion Criteria

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

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Part 1: Dose Escalation		Drug: STX-721/PFL-721 (Escalated) STX-721/PFL-721 dose will be escalated per cBLRM-design.
Experimental Part 2: RP2D Selection		Drug: STX-721/PFL-721 (3 dose levels) Participants will receive STX-721/PFL-721 at one of three dose levels.
Experimental Part 3: Dose Expansion		Drug: STX-721/PFL-721 (RP2D) Participants will receive the RP2D of STX-721/PFL-721.

Recruiting Locations

City of Hope
Duarte, California 91010

City of Hope
Huntington Beach, California 92648

City of Hope
Irvine, California 92618

Levine Cancer Institute - Charlotte
Charlotte, North Carolina 28204-2990

Thomas Jefferson University Research Facility
Philadelphia, Pennsylvania 19107

SCRI Oncology Partners - PPDS
Nashville, Tennessee 37203

University of Texas MD Anderson Cancer Center
Houston, Texas 77030-4009

University of Utah - Huntsman Cancer Institute - PPDS
Salt Lake City, Utah 84112-5550

NEXT Virginia
Fairfax, Virginia 22031-2171

More Details

NCT ID: NCT06043817
Status: Recruiting
Sponsor: Pierre Fabre Medicament

Study Contact

Adele De MASSON, clinical devlopment director, MD, PhD
33 772344916
PFL721_medical.team@pierre-fabre.com