STX-241 for Lung Cancer

(STX-241 FIH Trial)

Recruiting at 15 trial locations

Overseen By Angela Cadou

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pierre Fabre Medicament

Must be taking: Third generation EGFR TKI

Must not be taking: CYP inducers, CYP inhibitors

Disqualifiers: Other targeted therapies, Rapid progressive disease, CNS metastases, Active infection, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

171 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, including EGFR-targeted TKIs within 7 days before starting STX-241 and other systemic anticancer therapies within 28 days or 5 half-lives before starting, whichever is shorter. Additionally, medications that are strong CYP1A2 or CYP3A4 inducers or inhibitors, and certain other drugs, must be stopped at least 5 half-lives before starting STX-241.

What data supports the effectiveness of the drug STX-241 for lung cancer?

The research suggests that chemotherapy, including drugs like paclitaxel, can improve survival and quality of life for patients with advanced non-small cell lung cancer, even those with poor performance status. Paclitaxel poliglumex, a related drug, has shown potential benefits by reducing toxicity and increasing drug concentration in tumors. ^{1 2 3 4 5}

What makes the drug STX-241 unique for treating lung cancer?

The research does not provide specific information about STX-241 (PFL-241) for lung cancer, so its unique features compared to existing treatments are not detailed. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that has stopped responding to third-generation EGFR TKI treatments due to specific mutations. Participants must have measurable disease and be able to perform daily activities without significant assistance.

Inclusion Criteria

My cancer has worsened despite treatment with a specific lung cancer medication.

At least one measurable target lesion according to RECIST v1.1

My tumor's genetic testing meets the study's requirements.

Exclusion Criteria

I am currently breastfeeding.

My side effects from previous treatments are not severe.

I have not had major surgery in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Backfilling (Phase Ia)

Participants receive oral STX-241 twice daily at fixed doses: 10 mg, 20 mg, 40 mg, 80 mg, 120 mg, 180 mg on a continuous dosing schedule

8-12 weeks

Dose Range Optimization (Phase Ib)

Participants receive oral STX-241 twice daily at fixed doses selected from Part 1 within the OBD-MTD range on a continuous dosing schedule

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• STX-241

Trial Overview The study tests STX-241, a new drug designed for NSCLC resistant to previous treatments. It's a first-in-human trial aiming to find the safest dose, understand how the body processes it, and see if it works against certain lung cancers.

Participant Groups

Group I: STX-241/PFL-241 Experimental Treatment 1 Intervention

Part 1: Dose Escalation and Backfilling components (Phase Ia) Participants will receive oral (PO) STX-241/PFL-241 twice daily (BID) at fixed doses: 10 mg, 20 mg, 40 mg, 80 mg, 120 mg, 180 mg on a continuous dosing schedule Part 2: Dose Range Optimization (Phase Ib). Participants will receive oral (PO) STX-241/PFL-241 twice daily (BID) at fixed doses selected from Part 1 within the OBD-MTD range for Part 2 on a continuous dosing schedule.

Who Is Running the Clinical Trial?

Pierre Fabre Medicament

Lead Sponsor

Trials

83

Recruited

90,400+

Marie-Andrée Gamache

Pierre Fabre Medicament

Chief Executive Officer

MBA from HEC Montréal

Dr. Núria Perez-Cullell

Pierre Fabre Medicament

Chief Medical Officer since 2022

PhD in Pharmacy from the University of Barcelona

Findings from Research

In a study involving chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) and impaired performance status, single-agent paclitaxel poliglumex (PPX) showed similar overall survival compared to standard treatments like vinorelbine or gemcitabine, with a median survival of 7.3 months for PPX versus 6.6 months for controls.

PPX was associated with fewer severe adverse events such as neutropenia and anemia, indicating a better safety profile, while also requiring less supportive care, making it a potentially more tolerable option for patients with limited life expectancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. O'Brien, ME., Socinski, MA., Popovich, AY., et al.[2022]

Chemotherapy has been shown to improve survival and quality of life in patients with advanced non-small cell lung cancer, including those with poor performance status (PS2), who historically have been underrepresented in clinical trials.

Recent studies indicate that PS2 patients can benefit from chemotherapy, with combination treatments like carboplatin and paclitaxel potentially offering better outcomes than single-agent therapies, without significantly increased toxicity compared to fitter patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer. Langer, C., Lilenbaum, R.[2019]

Patients with performance status (PS) 2, who make up 30%-40% of advanced non-small-cell lung cancer (NSCLC) cases, have historically been excluded from clinical trials, limiting treatment options.

Recent studies suggest that systemic chemotherapy may benefit PS 2 patients, but advancements in biologic agents have not yet translated into improved outcomes for this group, as they often remain underrepresented in research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New treatment strategies in patients with advanced non-small-cell lung cancer and performance status 2. Rodriguez, E., Lilenbaum, RC.[2018]

In a study involving 400 chemotherapy-naive patients with performance status 2 non-small cell lung cancer, the combination of paclitaxel poliglumex (PPX) and carboplatin showed similar overall survival rates compared to the standard paclitaxel and carboplatin regimen, with a median survival of approximately 8 months for both treatments.

PPX/carboplatin resulted in fewer side effects such as alopecia and cardiac events, although it did show a trend towards increased grade 3 neuropathy, indicating a potentially safer profile despite not improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. Langer, CJ., O'Byrne, KJ., Socinski, MA., et al.[2022]

Preoperative chemotherapy with the MVP regimen (mitomycin, vindesine or vinblastine, and high-dose cisplatin) resulted in a high major response rate of 77% in patients with stage IIIa (N2) non-small cell lung cancer, leading to significant tumor reduction before surgery.

Patients who achieved a complete resection after chemotherapy had a median survival of 27 months, with 41% surviving at 3 years, highlighting the importance of surgical intervention following a major response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative chemotherapy for stage IIIa (N2) lung cancer: the Sloan-Kettering experience with 136 patients. Martini, N., Kris, MG., Flehinger, BJ., et al.[2019]

Oral administration of the cytostatic drugs etoposide and ifosfamide has shown modest efficacy in treating non-small cell lung cancer, with response rates of 17% and 18% respectively, indicating that oral routes can be a viable alternative to intravenous administration.

Among 26 new investigational drugs, several, including campthothecin-11, gemcitabine, and vinorelbine, have demonstrated promising response rates above 20% in previously untreated patients, suggesting potential new treatment options for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of non-small cell lung cancer: new cytostatic agents. Sorensen, JB.[2019]

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and 2-year survival rates of about 15%.

Preliminary studies indicate that triplet therapy may enhance survival rates compared to double therapy, with toxicity rates being low enough to support the development of these three-drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. Bunn, PA.[2005]

Over the past two decades, the addition of cisplatin-based regimens has led to modest improvements in chemotherapy for non-small cell lung cancer, with several new agents like navelbine and taxanes showing significant activity in Phase II and III testing.

Future treatments may involve combining these new drugs with targeted therapies that specifically attack unique characteristics of non-small cell lung cancer cells, potentially enhancing efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New chemotherapy agents in the treatment of advanced non-small cell lung cancer: an update including data from the Seventh World Conference on Lung Cancer. Comis, RL., Friedland, DM.[2019]

Lung cancer is the leading cause of cancer-related deaths in Europe and North America, with non-small cell lung cancer (NSCLC) making up 70-80% of cases, and current chemotherapy treatments show limited effectiveness with overall response rates below 20%.

The Southern Italy Cooperative Oncology Group is exploring new triplet chemotherapy combinations involving cisplatin and two additional agents, aiming to improve patient outcomes in advanced NSCLC, with ongoing phase I, II, and III trials evaluating the safety and efficacy of these new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. Frasci, G., Panza, N., Comella, G., et al.[2022]

The combination chemotherapy regimen PPM (cisplatin, peplomycin, mitomycin C) achieved a 44% overall response rate in patients with inoperable non-small cell lung cancer (NSCLC) and a median survival time of over 23.3 months for those who responded.

In comparison, the PFM regimen (cisplatin, 5FU, mitomycin C) resulted in a 35% response rate and a median survival time of 18.7 months for adenocarcinoma responders, indicating significant advancements in NSCLC treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current status in the treatment of inoperable non-small cell lung cancer (NSCLC)]. Nishimura, M., Sugiura, T., Urata, A., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

New treatment strategies in patients with advanced non-small-cell lung cancer and performance status 2. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Preoperative chemotherapy for stage IIIa (N2) lung cancer: the Sloan-Kettering experience with 136 patients. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Treatment of non-small cell lung cancer: new cytostatic agents. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. [2005]

8. Ireland pubmed.ncbi.nlm.nih.gov

New chemotherapy agents in the treatment of advanced non-small cell lung cancer: an update including data from the Seventh World Conference on Lung Cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Current status in the treatment of inoperable non-small cell lung cancer (NSCLC)]. [2013]