EGFR/HER2 Exon 20 Insertion Mutation, Non-Small Cell Lung Cancer, NSCLC
Conditions
Keywords
Exon 20, EGFR, HER2, NSCLC, TKI
Brief summary
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.
Interventions
DRUGSTX-721/PFL-721 (Escalated)
STX-721/PFL-721 dose will be escalated per cBLRM-design.
DRUGSTX-721/PFL-721 (3 dose levels)
Participants will receive STX-721/PFL-721 at one of three dose levels.
DRUGSTX-721/PFL-721 (RP2D)
Participants will receive the RP2D of STX-721/PFL-721.
Sponsors
Pierre Fabre Medicament
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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/PFL-721 | 1 year |
| Part 2 RP2D Selection: AUC(0-inf) of STX-721/PFL-721 | 1 year |
| Part 2 RP2D Selection: AUC(0-t) of STX-721/PFL-721 | 1 year |
| Part 2 RP2D Selection: AUC(0-τ) of STX-721/PFL-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 CR based on RECIST v1.1 per investigator assessment. | 1 year |
Countries
France, Germany, Netherlands, South Korea, Spain, Taiwan, United States
Contacts
CONTACTAdele De MASSON, clinical devlopment director, MD, PhD
Outcome results
None listed