Informations générales (source: ClinicalTrials.gov)
Phase I/II First-In-Human Open-label Trial to Assess Safety and Efficacy of STX-241 in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Resistant to EGFR Tyrosine Kinase Inhibitors (TKIs).
Interventional
Phase 1/Phase 2
Pierre Fabre Medicament (Voir sur ClinicalTrials)
septembre 2024
juillet 2030
15 septembre 2025
The goal of this First-In-Human (FIH) Phase I/II trial is to establish the safety
profile, determine the Recommended Phase II Dose (RP2D), explore the pharmacokinetic (PK)
exposure and pharmacodynamic (PD) properties as well as assess the efficacy of
STX-241/PFL-241, a mutant selective Central Nervous System (CNS)-penetrant fourth
generation EGFR TKI, in participants with locally advanced or metastatic NSCLC that
progressed during or following third generation EGFR TKI such as osimertinib due to C797X
double acquired (secondary) mutations.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Léon Bérard - 69008 - Lyon - France | Contact (sur clinicalTrials) | ||||
| CHU Hôpital de la Timone - 13385 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de l'Ouest (ICO) - René Gauducheau - 44800 - Saint-Herblain - France | Contact (sur clinicalTrials) | ||||
| Institut Universitaire du Cancer de Toulouse - Oncopole - 31059 - Toulouse - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
1. Signed and dated informed consent for participation in the trial obtained according
to International Council for Harmonisation of Technical Requirements of
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP), and national/local
regulations.
2. Male or female ≥ 18 years of age at the time of signing informed consent.
3. 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.
4. Part 1&2 Disease progression on a 3rd generation EGFR TKI-based therapy (monotherapy
or in combination) received at any prior line of treatment.
5. 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.
6. Part 1 (Backfilling component), Part 2: At least one measurable target lesion
according to RECIST v1.1.
7. Eastern cooperative oncology group (ECOG) performance status 0-1.
8. Adequate organ function as defined below:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelets ≥ 75 x 10^9/L
- Hemoglobin ≥ 90 g/L.
- Serum total bilirubin ≤ 1.5 x ULN or ≤ 3.0 × ULN for participants with
documented Gilbert's syndrome.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x
ULN. If the participant has liver metastases, AST and ALT ≤5 × ULN.
- Estimated glomerular filtration rate (GFR) ≥ 50 mL/min by CKD-EPI equation
9. Adequate cardiac function as defined below:
- Mean QT interval corrected for heart rate according to Fridericia's formula
(QTcF) value ≤ 470 msec for women and ≤ 450 msec for men and no history of long
QT syndrome or risk factors for torsade de pointe.
- Left ventricular ejection fraction (LVEF) ≥ 50% .
- Systolic blood pressure < 150 mmHg and diastolic blood pressure < 100 mmHg
10. Female participants of childbearing potential:
- Negative highly sensitive serum β-HCG test performed within 7 days prior to
first dose of STX-241 (C1D1) and a negative urine pregnancy test performed
prior to C1D1.
- Agreement to use one highly effective contraceptive method (as defined in
protocol and according to local regulations), starting at screening period,
throughout the trial and until at least 182 days (i.e. more than 5 estimated
STX- 241 half-lives (2 days) plus 6 months (180 days)) after the last dose of
STX-241. If the highly effective method of contraception is a hormonal
contraceptive method, it must be supplemented by one additional effective
(barrier) method of contraception.
- Agreement to not donate eggs (ova, oocytes) for the purpose of assisted
reproduction during the trial and for a period of 182 days after the last dose
of STX-241.
Note: a female participant of childbearing potential is a woman who is not
permanently sterilized or not postmenopausal (postmenopausal is defined as 12 months
with no menses without an alternative medical cause).
11. Male participants/partners with female spouse/partners of childbearing potential
must agree to take appropriate precautions to avoid fathering a child, i.e.:
- Consistently use a barrier method [e.g., condom with spermicidal foam / gel /
film /cream/suppository], and his female partner use a highly effective method
of contraception as defined in protocol and according to local regulations),
starting at screening and continuing throughout the trial period and for 92
days (ie. more than 5 estimated STX-241 half-lives (2 days) plus 3 months (90
days)) after the last dose of STX-241.
- Not donate sperm from Day 1 (first administration of STX-241) until at least 92
days after the last dose of STX-241.
NOTE: Other protocol defined inclusion criteria may apply.
1. Signed and dated informed consent for participation in the trial obtained according
to International Council for Harmonisation of Technical Requirements of
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP), and national/local
regulations.
2. Male or female ≥ 18 years of age at the time of signing informed consent.
3. 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.
4. Part 1&2 Disease progression on a 3rd generation EGFR TKI-based therapy (monotherapy
or in combination) received at any prior line of treatment.
5. 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.
6. Part 1 (Backfilling component), Part 2: At least one measurable target lesion
according to RECIST v1.1.
7. Eastern cooperative oncology group (ECOG) performance status 0-1.
8. Adequate organ function as defined below:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelets ≥ 75 x 10^9/L
- Hemoglobin ≥ 90 g/L.
- Serum total bilirubin ≤ 1.5 x ULN or ≤ 3.0 × ULN for participants with
documented Gilbert's syndrome.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x
ULN. If the participant has liver metastases, AST and ALT ≤5 × ULN.
- Estimated glomerular filtration rate (GFR) ≥ 50 mL/min by CKD-EPI equation
9. Adequate cardiac function as defined below:
- Mean QT interval corrected for heart rate according to Fridericia's formula
(QTcF) value ≤ 470 msec for women and ≤ 450 msec for men and no history of long
QT syndrome or risk factors for torsade de pointe.
- Left ventricular ejection fraction (LVEF) ≥ 50% .
- Systolic blood pressure < 150 mmHg and diastolic blood pressure < 100 mmHg
10. Female participants of childbearing potential:
- Negative highly sensitive serum β-HCG test performed within 7 days prior to
first dose of STX-241 (C1D1) and a negative urine pregnancy test performed
prior to C1D1.
- Agreement to use one highly effective contraceptive method (as defined in
protocol and according to local regulations), starting at screening period,
throughout the trial and until at least 182 days (i.e. more than 5 estimated
STX- 241 half-lives (2 days) plus 6 months (180 days)) after the last dose of
STX-241. If the highly effective method of contraception is a hormonal
contraceptive method, it must be supplemented by one additional effective
(barrier) method of contraception.
- Agreement to not donate eggs (ova, oocytes) for the purpose of assisted
reproduction during the trial and for a period of 182 days after the last dose
of STX-241.
Note: a female participant of childbearing potential is a woman who is not
permanently sterilized or not postmenopausal (postmenopausal is defined as 12 months
with no menses without an alternative medical cause).
11. Male participants/partners with female spouse/partners of childbearing potential
must agree to take appropriate precautions to avoid fathering a child, i.e.:
- Consistently use a barrier method [e.g., condom with spermicidal foam / gel /
film /cream/suppository], and his female partner use a highly effective method
of contraception as defined in protocol and according to local regulations),
starting at screening and continuing throughout the trial period and for 92
days (ie. more than 5 estimated STX-241 half-lives (2 days) plus 3 months (90
days)) after the last dose of STX-241.
- Not donate sperm from Day 1 (first administration of STX-241) until at least 92
days after the last dose of STX-241.
NOTE: Other protocol defined inclusion criteria may apply.
1. Participant 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.
2. Participant with rapid progressive disease eligible to receive a platinum-based
chemotherapy.
3. Participant unable ingest or digest tablets. This can be caused by any impaired
gastrointestinal function or disease, such as for example: ulcerative diseases,
malabsorption syndrome, small bowel resection, ileus, etc. or any condition causing
uncontrolled nausea, vomiting or diarrhea.
4. 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 - Examples include, but are
not limited to, completely resected basal cell carcinoma and squamous cell
carcinoma of skin, melanoma in situ, curatively treated prostate cancer, breast
cancer and early gastric cancer cured by endoscopic mucosal resection or
endoscopic submucosal dissection.
5. 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 2 weeks prior to enrollment in the
trial.
6. History of hypersensitivity to active or inactive ingredients of STX-241, or drugs
with a similar chemical structure or from the same class.
7. Active, bacterial, fungal, or viral infection, including, but not limited to:
Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and known Human Immunodeficiency
Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS)-related illness,
tuberculosis or an infection requiring systemic therapeutic treatment within 2 weeks
prior to Day 1 (first administration of STX-241).
Note: Participants with known HIV infection are permitted if they have controlled
infection (undetectable viral load [HIV ribonucleic acid polymerase chain reaction
(PCR)] and CD4 count >350 either spontaneously or on a stable antiviral regimen).
For participants with controlled HIV infection, monitoring will be performed per
local standards.
8. Positive SARs-CoV-2 or variants of SARs-CoV2 RT-PCR test or suspected to be infected
with SARs-CoV2 or variants of SARsCoV2 with confirmation pending within 2 weeks of
first dose of STX-241.
9. Impaired cardiovascular function or clinically significant cardiovascular disease
(either active or within 6 months prior to signing informed consent), including any
of the following:
- Myocardial infarction, acute coronary syndromes including unstable angina,
coronary/peripheral artery bypass graft, coronary angioplasty or stenting.
- Symptomatic congestive heart failure (New York Heart Association Classification
Class ≥ II).
- Cerebrovascular accident or transient ischemic attack.
- Symptomatic bradycardia, requirement for anti-arrhythmic medication.
- Ongoing cardiac dysrhythmias of NCI-CTCAE Grade ≥2.
10. Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection or psychiatric illness/social situation that would limit compliance with
trial requirements.
11. Past medical history of Interstitial Lung Disease (ILD), drug-induced ILD, radiation
pneumonitis that required steroid treatment, or any evidence of clinically active
ILD.
12. Past medical history of Stevens-Jonhson Syndrome (SJS) or Toxic epidermal necrolysis
(TEN) or any evidence of clinically active SJS/TEN.
13. Women who are breast feeding.
14. Prior anticancer therapy:
- EGFR-targeted TKI within 7 days prior to the first dose of STX-241.
- Any other systemic anticancer therapy within 28 days or 5 half-lives prior to
the first dose of STX-241, whichever is the shortest, but with a minimum of 14
days in all circumstances.
- Radiotherapy to a large field or including a vital organ (including whole brain
radiotherapy or stereotactic radiosurgery to brain) within 14 days before the
first dose of STX-241.
15. Live attenuated vaccine received within 30 days prior to the first dose of STX-241.
16. Any toxicities from prior therapy with a NCI-CTCAE Grade ≥1 at the time of the first
dose of STX-241 (C1D1). Exceptions include alopecia (any grade), fatigue with a
Grade ≤2, and peripheral neuropathy with a Grade ≤2.
17. Major surgical procedure within 14 days of the first dose of STX-241 (procedures
such as central venous catheter placement, tumor needle biopsy, and feeding tube
placement are not considered major surgical procedures). Sequelae of surgical
procedures must have resolved, including adequate wound healing, prior to the first
dose of STX-241.
18. 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 substrates and 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.
19. Participation in a clinical trial with administration of an investigational drug
within 5 half-lives plus 14 days of the investigational drug, before the first dose
of STX-241.
20. 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.
21. Employee or family member of the investigator or site staff.
NOTE: Other protocol defined exclusion criteria may apply.