Neoadjuvant Envafolimab Plus Disitamab Vedotin and Carboplatin in Resectable HER2-Mutant Non-Small-Cell Lung Cancer

NCT06734182 | Recruiting Phase 2

• 1 other identifier: SMA-NSCLC-013
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Stage II-IIIB; HER2-Mutant; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• MPR rate

  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.

  up to 7 weeks after neoadjuvant

Secondary Outcomes (6)

• 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

Other Outcomes (1)

• Exploratory analysis of potential biomarkers related with the outcome

  up to 3 years

Study Arms (1)

Intervention/Treatment

EXPERIMENTAL

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

Drug: Envafolimab injections+intravenous Disitamab Vedotin+carboplatin

Interventions

Envafolimab injections+intravenous Disitamab Vedotin+carboplatin DRUG

Biological: Envafolimab 300 mg by subcutaneous injections every 3 weeks (Q3W), given on cycle day 1; Biological: Disitamab Vedotin 2.5mg/kg by IV infusion Q3W, given on cycle day 1;Drug: Corboplatin AUC 5 by IV infusion Q3W, given on cycle day 1;

Intervention/Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study;
• Pulmonary function being able to withstand the planned surgery evaluated by surgeons;
• Women of childbearing potential must undergo a serum pregnancy test within 3 days prior to the first dose and the result must be negative. Female patients of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug

You may not qualify if:

• 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);
• Previous use of PD-1/PD-L1 agent or the drug acting on another targeted T cell receptor (e.g., CTLA-4, OX-40);
• Severe allergic reaction to other monoclonal antibodies;
• Known serious or uncontrolled pre-existing diseases; including but not limited to cardiovascular events with hemodynamic instability, symptomatic cerebrovascular events, and hepatic cirrhosis above Child-Pugh A within 6 months;
• Other malignant tumors within 5 years prior to the first dose, except non-small cell lung cancer. The malignant tumors with negligible risk of metastasis or death (e.g., expected disease-free survival \> 5 years) and expected to achieve radical outcomes after treatment (e.g., sufficiently treated carcinoma in situ of cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated for radical surgery) can be excluded

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Study Sites (1)

Guangdong Provincial People's Hospital

Guangzhou, China

RECRUITING

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

Central Study Contacts

Wenzhao Zhong

CONTACT

020-83525975; syzhongwenzhao@scut.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No Masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single group assignment

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: December 16, 2024
• Study Start: June 22, 2024
• Primary Completion (Estimated): June 22, 2027
• Study Completion (Estimated): June 22, 2028
• Last Updated: December 16, 2024

Record last verified: 2023-12

Locations

CN (1)