Trial Title:
Study of FIH of STX-241 in Locally Advanced or Metastatic NSCLC Resistant to EGFR TKIs
NCT ID:
NCT06567015
Condition:
Non-small Cell Lung Cancer (NSCLC)
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Conditions: Keywords:
non-small cell lung cancer
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
STX-241
Description:
Film-coated tablet
Route of administration: Oral
Arm group label:
STX-241
Summary:
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, 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.
Criteria for eligibility:
Criteria:
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. Part 3 Disease
progression after a 3rd generation EGFR TKI-based therapy (1st line or 2nd line as
monotherapy or in combination) received as last therapy (see molecular
prescreening).
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.
- Part 3:
- Presence of C797X and absence of T790M mutations confirmed centrally on a
sample (blood or tissue) collected at molecular prescreening prior to
enrollment.
- Able to provide a blood sample for central molecular pre-screening and
agreeing for providing archival tissue or a fresh biopsy in case of
discordance between local and central molecular testings.
6. Part 1 (Backfilling component), Parts 2 & 3: 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.
9. Adequate cardiac function.
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.
Exclusion Criteria:
1. 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.
2. 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.
3. Uncontrolled CNS metastases or spinal cord compression 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.
4. History of hypersensitivity to active or inactive ingredients of STX-241, or drugs
with a similar chemical structure or from the same class.
5. 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.
6. 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.
7. 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.
8. Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection or psychiatric illness/social situation that would limit compliance with
trial requirements.
9. Past medical history of Interstitial Lung Disease (ILD), drug-induced ILD, radiation
pneumonitis that required steroid treatment, or any evidence of clinically active
ILD
10. Past medical history of Stevens-Jonhson Syndrome (SJS) or Toxic epidermal necrolysis
(TEN) or any evidence of clinically active SJS/TEN
11. Woman who are breast feeding.
12. 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.
13. Live attenuated vaccine received within 30 days prior to the first dose of STX-241.
14. Any toxicities from prior therapy greater than NCI-CTCAE Grade ≤1 at the time of the
first dose of STX-241. Exceptions include any grade alopecia, fatigue, and Grade ≤2
peripheral neuropathy.
15. 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.
16. 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.
17. 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.
18. 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.
19. Employee or family member of the investigator or site staff.
NOTE: Other protocol defined exclusion criteria may apply.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Melissa Johnson, Dr.
Facility:
Name:
Shanghai East Hospital, Tongji University
Address:
City:
Shanghai
Zip:
200120
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Caicun Zhou, Prof.
Facility:
Name:
Tianjin Medical University Cancer Institute and Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Huang Dingzhi, Prof.
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Aurelie Swalduz, Dr.
Facility:
Name:
CHU Hôpital de la Timone
Address:
City:
Marseille
Zip:
13385
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Pascale Tomasini, Dr.
Facility:
Name:
Institut de Cancérologie de l'Ouest (ICO) - René Gauducheau
Address:
City:
Saint-Herblain
Zip:
44800
Country:
France
Status:
Recruiting
Contact:
Last name:
Sandrine Hiret, Dr.
Facility:
Name:
Institut Universitaire du Cancer de Toulouse - Oncopole
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Julien Mazieres, Prof.
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94800
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
David Planchard, Prof.
Facility:
Name:
Universitätsklinikum Carl Gustav Carus Dresden
Address:
City:
Dresden
Zip:
1307
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Martin Wermke, Prof.
Facility:
Name:
Netherlands Cancer Institute
Address:
City:
Amsterdam
Zip:
1066 CX
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Gerrina Ruiter, MD PhD.
Facility:
Name:
Vall d'Hebron Institut d'Oncologia
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Enriqueta Felip Font, MD PhD.
Facility:
Name:
Hospital Universitario La Paz
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Javier de Castro Carpeno, Dr.
Facility:
Name:
Centro Integral Oncológico Clara Campal (CIOCC)
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Maria-Jose de Miguel-Luken, MD PhD.
Facility:
Name:
Taipei Veterans General Hospital
Address:
City:
Taipei
Zip:
11217
Country:
Taiwan
Status:
Not yet recruiting
Contact:
Last name:
Yung-Hung Luo, Dr.
Start date:
September 17, 2024
Completion date:
July 2030
Lead sponsor:
Agency:
Pierre Fabre Medicament
Agency class:
Industry
Source:
Pierre Fabre Medicament
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06567015
https://clinicaltrials.pierre-fabre.com/en/our-commitments
