STX-241 for Non-small cell lung cancer (NSCLC) — locally advanced or metastatic, resistant to EGFR tyrosine kinase inhibitors (TKIs)

Inclusion criteria

• {"criterion_text":"- Histological confirmation of locally advanced or metastatic, EGFR-mutant (ex19del or L858R mutations) non-small cell lung cancer (NSCLC) Stage IIIB/C or IV (AJCC 8th edition) not eligible for curative intent surgery or chemoradiation.\n- Part 1 and 2: Disease progression after a 3rd generation EGFR TKI-based therapy (monotherapy or in combination) received at any prior line of treatment.\n- Tumor mutation profile: Part 1 (backfilling component) and Part 2: Presence of C797X and absence of T790M mutations documented locally (as part of clinical practice) on a sample (blood or tissue) collected after progression on treatment with 3rd generation EGFR TKI.\n- Part 1 (backfilling component) and Parts 2: At least one measurable target lesion according to RECIST v1.1.\n- Eastern cooperative oncology group (ECOG) performance status 0-1.\n- Adequate hematologic function as defined by the laboratory parameters specified in the protocol\n- Adequate cardiac function as specified in the protocol"}

Exclusion criteria

• {"criterion_text":"- History of a primary malignancy other than NSCLC with the exception of: - Participants with a previous malignancy that completed all anticancer treatment at least 2 years before signing informed consent and with no evidence of residual disease from the prior malignancy at screening. - Malignancies with a negligible risk of metastasis or death (i.e. 5-year overall survival rate > 90%) that are adequately treated as specified in the protocol.\n- Spinal cord compression or CNS metastases that are associated with progressive neurological symptoms or require increasing doses of corticosteroids to control the CNS disease. If a participant requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks preceding enrollment in the trial.\n- Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD\n- Past medical history of Stevens-Jonhson Syndrome (SJS) or Toxic epidermal necrolysis (TEN) or any evidence of clinically active SJS/TEN\n- Treatment with a prohibited medication or herbal remedy known to be strong CYP1A2 or CYP3A4 inducers, strong CYP1A2 or CYP3A4 inhibitors, sensitive CYP1A2, CYP2B6 and CYP3A4 substrates, sensitive MATE1 and OATP1B1 substratesand proton pump inhibitors (PPI) and H2 antagonists unless discontinued prior to the first administration of STX-241 within the following timeframe: - At least 5 half-lives plus 14 days for strong CYP inducers. - At least 5 half-lives for CYP inhibitors, CYP/transporter substrates, proton pump inhibitor (PPI) and H2 antagonists.\n- Participants candidate for targeted therapies available to them such as, but not limited to, therapies targeting ALK, BRAF, MET, NTRK, ROS1) as identified by local testing performed after progression to the last line of systemic therapy.\n- Participant with rapid progressive disease eligible to receive a platinum-based chemotherapy"}

Primary endpoints

• {"endpoint_text":"- Part 1: Safety: Incidence and severity of TEAEs/SAEs including changes in physical examination, vital signs, laboratory values, LVEFs and ECGs, according to NCI-CTCAE v5.0 criteria.\n- Part 1: Tolerability: TEAEs/SAEs leading to STX-241 dose reductions, interruptions or discontinuations.\n- Part 1: OBD: Incidence of DLTs during Cycle 1, PK exposure, tumor shrinkage, TEAEs/SAEs ≥ Grade 2. Type, frequency, and severity of TEAEs/SAEs according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria.\n- Part 1: MTD: Incidence of Dose-Limiting Toxicities (DLTs) during Cycle 1 (i.e. the first 28 days of treatment per dose level).\n- Part 2: Overall safety, PK exposure, PD, confirmed ORR (cORR)by IR\n- Part 2: Safety: incidence and severity of TEAEs/SAEs including changes in laboratory values, physical examination, vital signs, LVEFs and ECGs according to NCI-CTCAE v5.0 criteria\n- Part 2: Tolerability: STX-241 dose reductions, interruptions or discontinuations.","definition_or_measurement_approach":"Measures and definitions provided in the protocol text: safety and tolerability assessed by incidence and severity of TEAEs/SAEs and changes in physical exam/vitals/labs/LVEF/ECG per NCI-CTCAE v5.0; OBD and MTD determined by incidence of DLTs during Cycle 1 (first 28 days); PK exposure measured by standard PK parameters; tumor response assessed by RECIST v1.1 and confirmed ORR by investigator review."}

Secondary endpoints

• {"endpoint_text":"- Part 1: PK exposure parameters (e.g. Cmax, Tmax, AUC0-tau, AUC0-t, AUC0-∞, t½, λz, CL/F, Vz/F, Rac for Cmax and AUC, and Ctrough).\n- Part 1: cORR, DCR, TTR and DOR by Investigator Review (IR) in accordance to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).\n- Part 2: DCR, TTR, DOR, and PFS by RECIST v1.1 by IR.\n- Part 2: Overall Survival (OS).\n- Part 2: PK exposure parameters (e.g. Cmax, Tmax, AUC0-tau, AUC0-t, AUC0-∞, t½, λz, CL/F, Vz/F, Rac for Cmax and AUC, and Ctrough).","definition_or_measurement_approach":"PK parameters defined by standard PK metrics (Cmax, Tmax, AUC variants, t½, λz, CL/F, Vz/F, Rac, Ctrough); tumor efficacy endpoints (cORR, DCR, TTR, DOR, PFS) assessed per RECIST v1.1 by Investigator Review; OS measured as overall survival."}

France

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

13-02-2026

Processing Time Days

598

Number Of Sites

5

Number Of Participants

27

Germany

Earliest CTIS Part Ii Submission Date

02-08-2024

Latest Decision Or Authorization Date

12-02-2026

Processing Time Days

559

Number Of Sites

1

Number Of Participants

5

Netherlands

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

540

Number Of Sites

1

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

549

Number Of Sites

5

Number Of Participants

16

Primary sponsor

Full Name

Pierre Fabre Medicament

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Labcorp Central Laboratory Services SARL

Responsibilities

Listed as third party; contact amy.walton2@labcorp.com; sponsorDuties codes: ["4"]

Name

Fortrea France S.A.R.L.

Responsibilities

Listed as third party; contact submissions@fortrea.com; sponsorDuties codes: ["1","10","11","12","2","3","5","6","7"]

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: [\"4\"], contact amy.walton2@labcorp.com","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Fortrea France S.A.R.L.","duties_or_roles":"sponsorDuties codes: [\"1\",\"10\",\"11\",\"12\",\"2\",\"3\",\"5\",\"6\",\"7\"], contact submissions@fortrea.com","organisation_type":"Pharmaceutical company"}