A clinical trial to learn about the safety and effects of STX-241, a new oral anticancer drug for the treatment of patients with advanced lung cancer- “STX-241 FIH study"

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pierre Fabre Medicament

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Sep 2024 → ongoing

Decision date (initial)

2024-09-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pierre Fabre Médicament

External identifiers

EU CT number

2023-510203-21-00

ClinicalTrials.gov

NCT06567015

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Pharmacokinetic, Therapy, Pharmacodynamic, Pharmacogenomic, Efficacy

Part 1: Characterize the safety and tolerability of STX-241.
Part 1: To determine the range of doses for Part 2, the optimal biologically active dose (OBD) and the maximum tolerated dose (MTD), of STX-241.
Part 2: Determine the Recommended Phase II Dose (RP2D) of STX-241.
Part 2: Further characterize the overall safety and tolerability of STX-241.

Secondary objectives 4

1. Part 1: Characterize the pharmacokinetic (PK) exposure profile of STX-241 and its metabolite M30.
2. Part 1: Evaluate preliminary anti-tumor activity of increasing dose levels of STX-241.
3. Part 2: Assess the anti-tumor activity of STX-241 at the selected dose levels in Part 1 within the range of OBD and MTD.
4. Part 2: Characterize the pharmacokinetic (PK) exposure profile of STX-241 and M30 (or its main metabolite(s) based on the exploratory metabolite identification performed in Part 1).

Conditions and MedDRA coding

locally advanced or metastatic non-small cell lung cancer (NSCLC) resistant to EGFR tyrosine kinase inhibitors (TKIs)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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.
2. Part 1: Disease progression after a 3rd generation EGFR TKI-based therapy (administered as monotherapy or in combination) received at any prior line of treatment. Part 2: Disease progression after a 3rd generation EGFR TKI-based therapy (administered as monotherapy or in combination) given as first or second line of prior systemic anti-cancer therapy and no more than 2 prior lines of systemic anti-cancer therapy.
3. Tumor mutation profile: Part 1 (backfilling component): 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 2: Presence of C797X mutation documented locally (as part of clinical practice) on a sample (blood or tissue) collected after progression on treatment with a 3rd generation EGFR TKI.
4. Part 1 (backfilling component) and Parts 2: At least one measurable target lesion according to RECIST v1.1.
5. Eastern cooperative oncology group (ECOG) performance status 0-1.
6. Adequate hematologic function as defined by the laboratory parameters specified in the protocol
7. Adequate cardiac function as specified in the protocol

Exclusion criteria 8

1. History of a primary malignancy other than NSCLC with the exception of: - Participants with a previous malignancy that completed all curative 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.
2. 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.
3. Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD
4. Past medical history of Stevens-Jonhson Syndrome (SJS) or Toxic epidermal necrolysis (TEN) or any evidence of clinically active SJS/TEN
5. 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.
6. Part 1: 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. Part 2: Participants candidate for targeted therapies available to them, such as but not limited to therapies targeting ALK, BRAF, MET (ex14 mutations or amplification), NTRK, ROS1, HER2 (mutation or amplification), as identified by local testing performed after progression to the 3rd generation EGFR TKI-based therapy.
7. Participant with rapid progressive disease eligible to receive a platinum-based chemotherapy
8. Part 2: Participants who received 1st or 2nd generation EGFR TKIs.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. 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.
2. Part 1: Tolerability: TEAEs/SAEs leading to STX-241 dose reductions, interruptions or discontinuations.
3. 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.
4. Part 1: MTD: Incidence of Dose-Limiting Toxicities (DLTs) during Cycle 1 (i.e. the first 28 days of treatment per dose level).
5. Part 2: Overall safety, PK exposure, PD, confirmed ORR (cORR)by IR
6. 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
7. Part 2: Tolerability: STX-241 dose reductions, interruptions or discontinuations.

Secondary endpoints 5

1. 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).
2. Part 1: cORR, DCR, TTR and DOR by Investigator Review (IR) in accordance to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
3. Part 2: DCR, TTR, DOR, and PFS by RECIST v1.1 by IR.
4. Part 2: Overall Survival (OS).
5. 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).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pierre Fabre Medicament

Sponsor organisation

Pierre Fabre Medicament

Address

Les Cauquillous

City

Lavaur

Postcode

81500

Country

France

Scientific contact point

Organisation

Pierre Fabre Medicament

Contact name

Medical Team

Public contact point

Organisation

Pierre Fabre Medicament

Contact name

Clinical Trial Information

Third parties 3

Locations

4 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications