Combination treatment for resectable HER2-mutant non-small cell lung cancer

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

This study is testing a new combination treatment for people with resectable HER2-mutant non-small cell lung cancer to see if it can improve their chances of recovery after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Guangdong Provincial People's Hospital (Academic / other)
• Drugs / interventions: immunotherapy, Envafolimab, Disitamab
• Locations: 1 site (Guangzhou)
• Trial ID: NCT06734182 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a combination therapy involving Envafolimab, Disitamab Vedotin, and Carboplatin in patients with resectable HER2-mutant non-small cell lung cancer (NSCLC) at stages II to IIIB. Participants will receive four cycles of treatment before undergoing surgical resection, with tumor samples collected for further analysis. The primary goal is to assess the major pathologic response rate, while also monitoring overall survival and minimal residual disease post-surgery. The study aims to provide insights into the effectiveness of this novel combination therapy in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are treatment-naive adults aged 18-75 with histologically confirmed resectable stage II to IIIB HER2-mutant NSCLC.

Not a fit: Patients with contraindications to immunotherapy or those with unresectable cancer will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the outcomes for patients with HER2-mutant non-small cell lung cancer.

How similar studies have performed: While there have been studies on HER2-targeted therapies in lung cancer, this specific combination approach is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Having sufficient understanding of this study and being willing to sign the informed consent form (ICF);
2. Aged 18-75 years, male or female;
3. 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.
4. PET-CT or CT plus MRI should be completed before enrollment;
5. HER2 mutations identified by histological specimens;
6. Measurable lesions based on the response evaluation criteria in solid tumors version 1.1 (RECIST v1.1);
7. 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);
8. ECOG score 0-1;
9. No contraindications to immunotherapy;
10. Adequate organ function:
11. Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study;
12. Pulmonary function being able to withstand the planned surgery evaluated by surgeons;
13. 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

Exclusion Criteria:

1. 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;
2. 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;
3. Previous treatment with systemic antitumor therapy for early NSCLC, including investigational product;
4. History of (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or ongoing pneumonitis/interstitial lung disease requiring steroid treatment;
5. Active tuberculosis;
6. Active infection requiring systemic treatment;
7. 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;
8. 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);
9. Known human immunodeficiency virus (HIV) infection (known positive HIV antibody);
10. 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);
11. Previous use of PD-1/PD-L1 agent or the drug acting on another targeted T cell receptor (e.g., CTLA-4, OX-40);
12. Severe allergic reaction to other monoclonal antibodies;
13. 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;
14. 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

Where this trial is running

Guangzhou

• Guangdong Provincial People's Hospital — Guangzhou, China (Recruiting)

Study contacts

• Study coordinator: Wenzhao Zhong

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