A Prospective, Single-arm, Multicenter, Phase II Clinical Study on Envafolimab Combined With Disitamab Vedotin And Carboplatin for Resectable, Stage II-III, HER2-Mutant Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Envafolimab injections+intravenous Disitamab Vedotin+carboplatin
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Guangdong Provincial People's Hospital
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- MPR rate
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a prospective, single-arm, multi-center, phase II clinical study to evaluate the efficacy and safety of Envafolimab injection (PD-L1) combined with Disitamab Vedotin (HER2 ADC) and Carboplatin for resectable, HER2-Mutant, stage II-IIIB, NSCLC.
Detailed Description
The eligible patients will receive 4 cycles of subcutaneous Envafolimab injections (300mg, d1, Q3W) in combination with intravenous Disitamab Vedotin (2.5mg/kg, d1, Q3W) and carboplatin (AUC5, d1, Q3W), followed by surgical resection 4-6 weeks after the last dose of neoadjuvant therapy. The tumor tissue samples collected from subjects during the study will be submitted to the authorized central laboratory for evaluation of pathological response and translational research. Dynamic blood samples will be collected at baseline, after neoadjuvant treatment and after surgery for tumor-informed minimal residual disease (MRD) testing. After surgery, patients will be provided with or without adjuvant therapy according to MRD results. Patients with postoperative positive MRD result will be provided with adjuvant treatment after multidisciplinary discussion. The primary endpoint of this study is major pathologic response (MPR) rate. All the subjects will be followed up for overall survival, until death, withdrawal of informed consent or end of study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Having sufficient understanding of this study and being willing to sign the informed consent form (ICF);
- •Aged 18-75 years, male or female;
- •Treatment-naive, histologically confirmed resectable, stage II, IIIA, IIIB (AJCC staging system, version 9) NSCLC; cTNM stage can be confirmed through PET-CT or pathological biopsy; N2 should be confirmed by mediastinoscopy or EBUS.
- •PET-CT or CT plus MRI should be completed before enrollment;
- •HER2 mutations identified by histological specimens;
- •Measurable lesions based on the response evaluation criteria in solid tumors version 1.1 (RECIST v1.1);
- •Tumor tissue specimens and blood sample available for detection of MRD and biomarkers (the tumor tissue specimens must be freshly obtained or archived samples within 3 months prior to enrollment);
- •ECOG score 0-1;
- •No contraindications to immunotherapy;
- •Adequate organ function:
Exclusion Criteria
- •Presence of locally advanced, unresectable or metastatic disease; unresectable includes the unresectable defined in the Chinese expert consensus on the multidisciplinary diagnosis and treatment for stage III non-small cell lung cancer (2019), including partial stage IIIA and IIIB and all the stage IIIC;
- •Participants with known EGFR sensitive mutations or ALK translocation, KRAS sensitive mutations, BRAF V600E, ROS1 fusions, RET fusions, MET exon 14 alterations and MET amplification, NTRK fusions;
- •Previous treatment with systemic antitumor therapy for early NSCLC, including investigational product;
- •History of (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or ongoing pneumonitis/interstitial lung disease requiring steroid treatment;
- •Active tuberculosis;
- •Active infection requiring systemic treatment;
- •Subjects with any known or suspected autoimmune disorder or immunodeficiency, with the following exceptions: hypothyroidism, hormone therapy is not needed, or well controlled at physiological dose; controlled type I diabetes;
- •Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen \[HBsAg\] in screening period with HBV-DNA detected higher than the upper limit of normal at the clinical laboratory of the study center); (the subjects with HBV-DNA assay \<500 IU/mL within 28 days prior to randomization who have received local standard antiviral therapy for at least 14 days and are willing to receive antiviral therapy continuously during the study can be enrolled); active hepatitis C (defined as positive hepatitis C surface antibody \[HCsAb\] in screening period and positive HCV-RNA);
- •Known human immunodeficiency virus (HIV) infection (known positive HIV antibody);
- •Vaccination of live vaccine within 30 days prior to the first dose. Including but not limited to the following: parotitis, rubella, measles, varicella/ herpes zoster (varicella), yellow fever, Rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine (inactivated virus vaccine allowed);
Arms & Interventions
Intervention/Treatment
Patients were treated with subcutaneous Envafolimab injections (300mg, d1, Q3W) combined with intravenous Disitamab Vedotin (2.5mg/kg, d1, Q3W) and carboplatin (AUC5, d1, Q3W) Participants receive totally 4 cycles of Envafolimab combined with Disitamab Vedotin and carboplatin during perioperative period
Intervention: Envafolimab injections+intravenous Disitamab Vedotin+carboplatin
Outcomes
Primary Outcomes
MPR rate
Time Frame: up to 7 weeks after neoadjuvant
Major Pathological Response (MPR) Rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes in neoadjuvant therapy.
Secondary Outcomes
- pCR rate(pCR:up to 7 weeks after neoadjuvant;)
- ORR(ORR:up to 7 weeks after neoadjuvant;)
- EFS(EFS up to 3 years)
- OS(OS up to 3 years)
- Safety evaluation of subjects(Safety: 90 days after the last administration)
- Molecular progression of ctDNA based on MRD monitoring(up to 3 years)