Efficacy and Safety Evaluation of PLB1004 in Patients With Non-squamous NSCLC Harboring EGFR Exon 20 Insertion.

Non-Small-Cell Lung Cancer Clinical Trial

Official title:

Randomized, Controlled, Open Label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of PLB1004 Versus Platinum-based Chemotherapy With or Without Sintilimab of Advanced NSCLC With EGFR Exon 20 Ins Mutations

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06281964
• Other study ID #: PLB1004-III-01
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 30, 2024
• Est. completion date: December 30, 2026

Study information

• Verified date: January 2024
• Source: Avistone Biotechnology Co., Ltd.
• Contact: Weizhe Xue
• Phone: +86-10-84148931
• Email: xueweizhe[@]avistonebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Efficacy and safety evaluation of PLB1004 in patients with locally advanced/metastatic non-squamous NSCLCharboring EGFR exon 20 insertion.

Description:

Randomized, controlled, open label, multicenter phase III study to evaluate the efficacy and safety of PLB1004 Versus platinum-based chemotherapy with or without Sintilimab in the first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) Exon 20 insertion(ex 20) mutations.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 327
• Est. completion date: December 30, 2026
• Est. primary completion date: January 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent document.

2. Aged at least 18 years old.

3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC (stage IIIB~IV).

4. Tumor tissue has written confirmation of EGFR by second generation sequencing (NGS) testing by a local laboratory or sponsor designated central laboratory accredited by the Clinical Laboratory Improvement Act Amendments (CLIA), International Organization for Standardization/Independent Ethics Committee (ISO/IEC), College of American Pathologists (CAP) (or other equivalent accreditation) Ex20ins is positive. Note: Considering that there are multiple subtypes of EGFR Ex20ins, the mutant subtypes to be included in the subjects should be representative and reflect the epidemiological distribution characteristics?Participants with EGFR ex20ins mutation.

5. At least one measurable lesion as defined by RECISTV1.1(Brain lesions were not included in measurable target lesions)

6. ECOG performance status 0 to 1.

7. Life expectancy is not less than 12 weeks.

8. No previous systemic treatment for locally advanced or metastatic non-squamous cell cancer NSCLC. Note: Subjects are allowed to receive neoadjuvant/adjuvant therapy as long as the relevant therapy has ended at least 6 months before the disease is diagnosed as locally progressive or metastatic tumors -

Exclusion Criteria:

1. Have one of the following previous anti-tumor treatments: prior to the first dose of PLB1004 a) Any anti-EGFR TKI for the EGFR ex20ins mutation.. b) Received Chinese patent drugs with anti-tumor indications within 1 week before administration of the first study drugReceived Chinese patent drugs with anti-tumor indications within 1 week before administration of the first study drug c) required administration of the multidrug and toxin efflux protein (MATE) transporter substrate metformin within 1 week before and during the first study drug administration d)Strong inhibitors or strong inducers of the cytochrome P450 3A4 enzyme (CYP3A4) were required within 1 week before and during the study e) required immunosuppressive medication within 2 weeks before or during the first dose of study drug f) Major surgery within 4 weeks prior to starting PLB1004 or who have not recovered from side effects of such procedure except for the biopsy of Thoracoscopy and the clinical test of Mediastinoscopy could = 7 days prior to starting PLB1004 g) Radiotherapy to lung fields and whole-brain fields =4 weeks prior to starting PLB1004. For all other anatomic sites, radiotherapy =2 weeks prior to starting PLB1004 or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions is not included.

2. Patients with spinal cord compression ,brain membrane metastasis and symptomatic central nervous system (CNS), who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study manage CNS symptoms.

3. Before randomization, patients did not recover from any toxicity and/or complications of previous chemotherapy, surgery, radiotherapy and other anti-cancer treatments, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for hair loss and irrecoverable permanent radiation damage

4. Did not recover from any toxicity and/or complications of previous anti-cancer treatments such as chemotherapy, surgery, and radiotherapy, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for alopecia and irrecoverable permanent radiation damage

5. A tendency to coagulopathy or bleeding, including an arterial or venous thromboembolic event (including a history of myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other major thromboembolism) within 6 months before randomization; Any life-threatening bleeding event (including the need for blood transfusion, surgical or local treatment, or continued medical therapy) or major vascular invasion was considered by the investigator to be bleeding prone

6. Severe cardiac disease, such as any serious arrhythmia (including ventricular arrhythmia, drug-refractory supraventricular and other arrhythmias), grade III or higher cardiac dysfunction (New York Heart Association [NYHA], see Appendix 4 for details), and left ventricular ejection fraction (LVEF) <50% on echocardiography;

7. Mean corrected QT intervals (QTcF) of three electrocardiograms during screening, calculated according to Fridericia's formula at rest, were >470 ms;

8. Presence of uncontrolled hypertension (treated systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg)

9. Dysphagia, or active digestive disease or major gastrointestinal surgery that may affect the administration or absorption of the study drug (e.g., ulcerative lesions, uncontrolled nausea, vomiting, diarrhea, and malabsorption syndromes);

10. Allergy or intolerance to the drug class and excipient components of the study drug

11. pregnant or nursing women.

12. Received live vaccine within 4 weeks before randomization; -

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Cancer

Intervention

Drug:
• PLB1004
Participants received oral PLB1004 240mg on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive oral PLB1004 240mg and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
• Pemetrexed+(carboplatin or Cisplatin)with or without Sintilimab
Participants received IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Sintilimab 200mg intravenously administered on day 1 q3w per investigator's decision. Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive oral PLB1004 and 500 mg/m^2 of pemetrexed on Day 1 q3w and Sintilimab 200mg intravenously administered on day 1 q3w per investigator's decision. until disease progression in the maintenance period.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Avistone Biotechnology Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	intracranial Progression-Free Survival(PFS)	Reference RECIST v1.1, intracranial PFS assessed by BICR and investigator	3 years
Other	second progression-free survival (PFS2)	Investigator-assessed second progression-free survival (PFS2)	3 years
Other	Assess the Quality of Healthy Living About Patients	Use the EQ-5D-5L scale to measure patients' quality of healthy living. It has 5 items (Mobility, Self-care, Usual activities, Pain/discomfort, Depression/anxiety). Each item contains 5 levels: 1= no difficulty, 2= slight difficulty, 3= moderate difficulty, 4= serious difficulty, 5= extremely serious difficulty. The higher the score has the worse the health. Then, the score calculation of the European Five-Dimensional Health Scale is based on the calculation formula published by the EuroQol Group. Based on 5 combinations of different severity levels, a score of 0 to 1 is obtained. 0 is the least healthy and 1 is the most healthy.	3 years
Other	EGFR Ex20ins status in tumor tissues and its relevance to the clinical efficacy of drugs	EGFR Ex20ins status in tumor tissues and its relevance to the clinical efficacy of drugs	3 years
Other	Gene mutation status in plasma ctDNA before and after medication, and its correlation with clinical efficacy	To assess the expression of circulating tumor DNA in ascites and blood, ctDNA was mesured at screen, cycle 3 and end of the study	3 years
Primary	Progression-Free Survival (PFS) by BICR	Progression-free survival (PFS) as assessed by a Blind Independent Center Review Committee (BICR) with reference to RECIST v1.1 for Solid tumors	3 years
Secondary	Progression-Free Survival (PFS) by the investigator	Refer to RECIST v1.1, PFS assessed by the investigator	2 years
Secondary	Intracranial Overall Response Rate(ORR)	To evaluate the intracranial Overall Response Rate(ORR)which is defined by investigator as the proportion of subjects with Intracranial disease confirmed best overall response of complete response or partial response per RECIST v 1.1.	3 years
Secondary	Duration of Response (DOR)	DOR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first.	3 years
Secondary	Disease Control Rate (DCR)	DCR is defined as the percentage of participants achieving complete or partial response or stable disease as defined per RECIST v 1.1	3 years
Secondary	Overall Survival (OS)	OS is defined as the time from the date of the first dose until the date of death due to any cause.	3 years
Secondary	Incidence of Treatment-Emergent Adverse Events (TEAEs)	A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug assessed by CTCAE v5.0	3 years
Secondary	Plasma concentrations of PLB1004 and metabolites may be combined with data from other clinical studies	Plasma concentrations of PLB1004 and metabolites may be combined with data from other clinical studies	3 years