About this trial
The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of CFT8919 capsules in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying EGFR mutations. The main questions it aims to answer are:
* What is the maximum tolerated dose (MTD) of CFT8919? * Does CFT8919 demonstrate antitumor activity in these patients?
Participants will:
* Take CFT8919 capsules at different doses. * Undergo regular assessments for safety, pharmacokinetics, and tumor response. Researchers will compare different dose levels to determine the best balance between safety and efficacy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Dose-Escalation and Dose-Expansion Phases: Patients with histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the EGFR-L858R mutation, who have failed standard treatment (disease progression or intolerance), lack standard treatment options, or are deemed unsuitable for standard treatment by the investigator, or have refused standard treatment.
Cohort A: Patients with locally advanced or metastatic NSCLC harboring the EGFR-L858R mutation who have experienced disease progression after third-generation EGFR-TKI treatment and carry secondary EGFR mutations (such as C797S, L718Q, G724S, S768I, etc.).
Cohort B: Patients with locally advanced or metastatic NSCLC harboring the EGFR-L858R mutation who have failed standard treatment or are unsuitable for or have refused standard treatment (patients with secondary EGFR mutations are prioritized for Cohort A).
• Dose-Escalation Phase requires evaluable lesions, while Dose-Expansion and Cohort-Expansion Phases require measurable lesions as defined by RECIST V1.1.
Disqualifiers
Prior or ongoing treatment with EGFR-L858R-targeted PROTAC therapies.
Less than 5 half-lives or 4 weeks (whichever is shorter) since the last anti-tumor treatment before the first dose of study drug; less than 6 weeks since the last treatment with nitrosoureas or mitomycin C; less than 1 week since the last anti-tumor herbal treatment.
Patients who underwent major surgery (as defined by the investigator) or experienced significant trauma within 4 weeks before the first dose of study drug; patients who received radiation therapy within 4 weeks prior to the first dose, except for palliative radiation (e.g., for bone metastases to control pain) that is unlikely to affect bone marrow function, which may allow inclusion 2 weeks post-radiation.
Patients with unstable central nervous system (CNS) metastases (those who have received treatment for brain metastases, have stable brain lesions, and have discontinued corticosteroids, anticonvulsants, or mannitol treatment for ≥2 weeks before the first dose may be considered for inclusion); patients with leptomeningeal metastases or spinal cord compression.
Trial design
Single group
Treatments tested in this trial
Dose-Escalation (Phase Ia) CFT8919 capsule
DrugPhase 1a,enrolled, eligible patients receive CFT8919 150-900mg twice daily.
Dose-Expansion (Phase Ib) CFT8919 capsule
DrugPhase 1b,enrolled, eligible patients receive CFT8919 RP2D twice daily.
Cohort-Expansion (Phase Ic) CFT8919 capsule
DrugPhase 1c,enrolled, eligible patients receive CFT8919 RP2D twice daily.
Treatment groups
Trial outcomes
Primary outcomes
Objective Response Rate (ORR)
The percentage of participants who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.
Maximum Tolerated Dose (MTD)
The highest dose at which no more than one of six participants experiences dose-limiting toxicity (DLT).
Recommended Phase II Dose (RP2D)
The dose selected for Phase II studies based on safety, tolerability, and efficacy data.
Secondary outcomes
Dose-Limiting Toxicities (DLTs)
The occurrence of adverse events that prevent further dose escalation.
Safety and Tolerability
Assessed by the frequency, type, and severity of adverse events (AEs) and serious adverse events (SAEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Peak Plasma Concentration (Cmax)
The maximum observed concentration of the drug in plasma.
Time to Reach Maximum Concentration (Tmax)
The time at which Cmax is observed
Sponsors and contacts
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