Envafolimab Immunotherapy After ctDNA EGFR Clearance by Treatment With Almonertinib in EGFR-Mutant, PD-LI Positive NSCLC

NCT05534113 | Unknown Phase 2

• 1 other identifier: 2022-SR-439
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, single-arm, open-label, interventional clinical study, aimed at exploring the efficacy and safety of sequential Envafolimab immunotherapy after patients with ctDNA EGFR mutation clearance and achieved stable radiographically deep esponse after first line treatment with Almonertinib in EGFR-Mutant, PD-LI positive non-small-cell lung cancer.

Conditions

Non-small Cell Lung Cancer

Keywords

EGFR; ctDNA; PD-L1; NSCLC

Outcome Measures

Primary Outcomes (2)

• PFS

  The progression-free survival is defined as the time from date of baseline until the the date of first documented progression or date of death from any cause, whichever came first.

  24 months.

• TRP

  Time to retest positive is defined as the time from date of sequential Envafolimab treatment until blood sample ctDNA detected for EGFR mutation recurrence or disease progression assessed by radiological imaging，assessed up to 24 months.

  24 months.

Secondary Outcomes (3)

• ORR

  From baseline, then every 6 weeks, until disease progression or discontinuation from study. ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression assessed up to 24 months.

• DCR

  24 months.

• OS

  24 months after the last subject participating in.

Study Arms (1)

sequential Envafolimab therapy after Almonertinib treatment

EXPERIMENTAL

Sequential Envafolimab therapy after patients with ctDNA EGFR mutation clearance and achieve stable radiographically deep response after treatment with Almonertinib

Drug: Almonertinib Envafolimab

Interventions

Almonertinib Envafolimab DRUG

Subjects will receive Almonertinib treatment for 6-8 weeks after enrollment, and receive ctDNA detection and radiography assessment again. If the EGFR mutation is positive, according to the patient's condition and clinical actual situation, subjects will receive combination therapy scheme, follow-up once every 6 weeks. The treatment will continue until the disease progress assessed by radiography. If the EGFR mutation turns negative and stable radiographically deep response, stop Almonertinib treatment and receive the relevant assessment before immunotherapy and receive Envafolimab treatment，and follow-up once every 6 weeks. The treatment of Envafolimab will continue until the EGFR mutation is positive again or disease progress assessed by radiography.

sequential Envafolimab therapy after Almonertinib treatment

Eligibility Criteria

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

You may qualify if:

• Over 18 years old (including 18 years old) .
• The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 to 1, and it has not deteriorated in the previous 2 weeks, and the minimum expected survival is 12 weeks.
• Unresectable advanced or metastatic non-squamous cell non-small cell lung cancer.
• Blood samples were confirmed to contain EGFR-sensitive mutations by ctDNA testing(including exon 19 deletion or L858R, both alone or coexist with other EGFR mutations.Patients with EGFR20 exon insertion mutations could not be enrolled).
• No systematic antitumor treatment before enrollment.
• PD-L1 expression is positive, defined as TPS (tumor proportion score) ≥10%.
• The patient has at least one tumor lesion that can be accurately measured at baseline, and the longest diameter at baseline is ≥10 mm (if it is a lymph node, the short diameter is required to be ≥15 mm). The selected measurement method is suitable for accurate repeat measurement, which can be computed tomography (CT) or magnetic resonance scan (MRI). If there is only one measurable lesion, it can be accepted as the target lesion, and a baseline assessment of the tumor lesion should be performed at least 14 days after the diagnostic biopsy.
• Women of childbearing age should take appropriate contraceptive measures from screening to 3 months after stopping the study treatment and should not breastfeed. Before starting the administration, the pregnancy test is negative, or meeting one of the following criteria proves that there is no risk of pregnancy:
• Postmenopausal is defined as age greater than 50 years，and amenorrhea for at least 12 months after stopping all exogenous hormone replacement therapy.
• For women younger than 50 years old, if the amenorrhea is 12 months or more after stopping all exogenous hormone treatments, and the luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels are within the laboratory postmenopausal reference value range, also It can be considered postmenopausal.
• Have received irreversible sterilization, including hysterectomy, bilateral ovariectomy or bilateral fallopian tube resection, except for bilateral fallopian tube ligation.
• Male subjects should use barrier contraception (ie, condoms) from screening to 3 months after the study treatment is stopped.
• The subjects themselves participated voluntarily and signed a written informed consent form.

You may not qualify if:

• Subjects who meet any of the following criteria cannot be included in this study:
• Have received any of the following treatments:
• Previously received antitumor treatment for lung cancer in the past;
• Previously received Chinese patent medicine with anti-tumor effect. If Chinese patent medicine with anti-tumor effect has been received for no more than 7 days, and the medicine has been stopped for 2 weeks or more before the drug treatment of this study, it can be included in the group.
• Patients who had received open surgery on other parts except lungs within 14 days before using the study drug ≤ 14 days.
• Refractory nausea, vomiting or chronic gastrointestinal diseases, inability to swallow the study drug or having undergone extensive intestinal resection may affect the full absorption of Almonertinib.
• Patients with other malignant tumors in recent 5 years (excluding completely resected basal cell carcinoma, bladder cancer in situ and cervical carcinoma in situ).
• Have a history of interstitial lung disease, a history of drug-induced interstitial lung disease, a history of interstitial pneumonia requiring steroid treatment, or any evidence of clinically active interstitial lung disease.
• As judged by the investigator, there are any serious or poorly controlled systemic disease, such as poorly controlled hypertension, active bleeding or active infection (including active fungal, bacterial and / or viral infections requiring systemic treatment or full-body anti infective drugs used within one week before the first administration).
• At the beginning of the study treatment, there were unresponsive residual toxicity from previous treatment that was greater than CTCAE grade 3, except for hair loss.
• Meet any of the following cardiac examination results:
• The average value of QT interval (QTcF) corrected by Fridericia's formula obtained from 3 ECG examinations at rest\> 470 msec;
• Resting ECG suggests that there are various clinically significant rhythms, conduction or ECG morphological abnormalities that are judged by the investigator (such as complete left bundle branch block, 3 degree atrioventricular block, 2 degree atrium Ventricular block and PR interval\> 250 msec, etc.);
• There are any factors that increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death or prolonged QT of immediate family members under 40 Any concomitant drugs in the interval;
• Left ventricular ejection fraction (LVEF) \<50%.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

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

• Yong Qian Shu

  Jiangsu Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• Wen Gao

  Jiangsu Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• Pei Ma

  Jiangsu Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongqian Shu, PhD

CONTACT

0086-025-68306428; shuyongqian@csco.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: September 9, 2022
• Study Start: December 1, 2022
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: September 14, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share