A Phase I Study of CFT8919 in Patients With Advanced NSCLC

NCT06641609 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: BTP-662212
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer With EGFR Mutation

Keywords

Non-small cell lung cancer; EGFR mutation

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR)

  The percentage of participants who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.

  up to 104 weeks

• Maximum Tolerated Dose (MTD)

  The highest dose at which no more than one of six participants experiences dose-limiting toxicity (DLT).

  Determined at the end of the dose-escalation phase，an average of 1 year

• Recommended Phase II Dose (RP2D)

  The dose selected for Phase II studies based on safety, tolerability, and efficacy data.

  Determined at the end of the dose-expansion，an average of 2 years

Secondary Outcomes (5)

• Dose-Limiting Toxicities (DLTs)

  At the end of Cycle 1 (each cycle is 28 days)

• Safety and Tolerability

  From the start of treatment until 28 days after the last dose

• Peak Plasma Concentration (Cmax)

  Up to approximately 30 months

• Time to Reach Maximum Concentration (Tmax)

  Up to approximately 30 months.

• Half-Life (t1/2)

  Up to approximately 30 months

Study Arms (3)

Dose-Escalation (Phase Ia)

EXPERIMENTAL

Intervention Name: CFT8919 capsule Intervention Type: Drug Intervention Description: Participants will receive CFT8919 at different dose levels in a "3+3" dose-escalation design, starting from 150 mg BID, increasing to 300 mg, 600 mg, and up to 900 mg BID.

Drug: Dose-Escalation (Phase Ia) CFT8919 capsule

Dose-Expansion (Phase Ib)

EXPERIMENTAL

After the MTD is determined in Phase Ia, participants will receive CFT8919 at the recommended Phase II dose (RP2D). The primary objective is to further evaluate the safety and preliminary antitumor activity of the drug at the RP2D

Drug: Dose-Expansion (Phase Ib) CFT8919 capsule

Cohort-Expansion (Phase Ic)

EXPERIMENTAL

Participants will be enrolled based on their EGFR mutation status into separate cohorts. Each cohort will receive CFT8919 at the RP2D to evaluate its efficacy, safety, and pharmacokinetic profile in specific EGFR mutation populations, including those with L858R and other EGFR-resistant mutations after EGFR-TKI treatment.

Drug: Cohort-Expansion (Phase Ic) CFT8919 capsule

Interventions

Dose-Escalation (Phase Ia) CFT8919 capsule DRUG

Phase 1a，enrolled, eligible patients receive CFT8919 150-900mg twice daily.

Also known as: CFT8919

Dose-Escalation (Phase Ia)

Dose-Expansion (Phase Ib) CFT8919 capsule DRUG

Phase 1b，enrolled, eligible patients receive CFT8919 RP2D twice daily.

Also known as: CFT8919

Dose-Expansion (Phase Ib)

Cohort-Expansion (Phase Ic) CFT8919 capsule DRUG

Phase 1c，enrolled, eligible patients receive CFT8919 RP2D twice daily.

Also known as: CFT8919

Cohort-Expansion (Phase Ic)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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-Expansion Phase: In addition to the above criteria, the following must also be met:
• 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.
• Age ≥18 years, no gender restrictions.
• Expected survival ≥12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ function, meeting the following criteria:
• Hematologic: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (1500/mm³), platelets ≥100 × 10⁹/L, hemoglobin ≥9 g/dL (90 g/L) without transfusion or hematopoietic growth factors within 14 days prior to screening.
• Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 × the upper limit of normal (ULN).
• Liver: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or ≤5.0 × ULN in the presence of liver metastases; total bilirubin (TBIL) ≤1.5 × ULN, or ≤3.0 × ULN in the presence of liver metastases or known Gilbert\'s syndrome (unconjugated hyperbilirubinemia).
• Kidney: Serum creatinine (Scr) ≤1.5 × ULN, or for patients with Scr \>1.5 × ULN, creatinine clearance (Ccr) ≥50 mL/min (calculated using the Cockcroft-Gault formula); urine protein ≤1+, or if ≥2+, 24-hour urine protein quantification showing \<1 g.
• Toxicity from prior anti-tumor treatments must have resolved to CTCAE grade ≤1 (except for toxicities that, in the investigator\'s judgment, are long-lasting and non-recoverable but pose no safety risk and are ≤2 in grade).
• Patients must have been previously diagnosed with the EGFR-L858R mutation via local testing. In the Dose-Escalation and Dose-Expansion Phases, patients who progressed on prior EGFR-TKI treatment must provide the genetic mutation results from their most recent EGFR-TKI treatment. For Cohort A patients, progression on third-generation EGFR-TKI treatment must have confirmed the presence of secondary EGFR mutations (e.g., C797S, L718Q, G724S, S768I) via tissue or blood tests.

You may not qualify if:

• 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.
• History of other primary malignancies within the past 3 years, except for malignancies that have been treated curatively with no known active disease and a low risk of recurrence, or adequately treated non-melanoma skin cancers, cervical carcinoma in situ, or papillary thyroid carcinoma.
• Clinically significant cardiovascular diseases, including but not limited to:
• a) Unstable angina, acute myocardial infarction, or New York Heart Association (NYHA) class II-IV heart failure;
• b) Ventricular arrhythmias or conduction disorders requiring clinical intervention (e.g., complete left bundle branch block, third-degree atrioventricular \[AV\] block, or second-degree AV block);
• c) Uncontrolled atrial fibrillation or atrial flutter;
• d) Prolonged QTcF interval (resting mean QTcF \>450 msec for men or \>470 msec for women);
• e) Left ventricular ejection fraction (LVEF) \<50% on echocardiography;
• f) Hypertension not controlled with medication.
• History of interstitial lung disease (ILD) or non-infectious pneumonitis.
• Adrenal insufficiency.
• Use of proton pump inhibitors, strong CYP3A4 inhibitors or inducers, or P-glycoprotein inhibitors or inducers within 7 days before the first dose.
• History of chronic diarrhea or diseases causing chronic diarrhea, such as Crohn\'s disease or irritable bowel syndrome, or any condition that might affect drug absorption (e.g., continuous diarrhea \>CTCAE grade 1 within 1 week prior to the first dose).
• Known severe hypersensitivity to the study drug or any of its excipients.

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (1)

浙江省杭州市拱墅区半山东路1号的英文翻译为： No. 1 Banshan East Road, Gongshu District, Hangzhou, Zhejiang Province, China

Hangzhou, Zhejiang, 310022, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• yun fan, PHD

  Zhejiang Cancer Hospital

  STUDY DIRECTOR

Central Study Contacts

yun fan, PHD

CONTACT

86-0571-88122092; fanyun@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: October 15, 2024
• Study Start: December 13, 2024
• Primary Completion: December 9, 2025
• Study Completion: April 3, 2026
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)