A Multicenter, Single-Arm, Prospective Phase II Clinical Study of Trastuzumab Rezetecan Combined With Radiotherapy in Patients With HER2-Mutated Oligoprogressive Advanced Non-Small Cell Lung Cancer

NCT07781202 | Not Yet Recruiting Phase 2

• 1 other identifier: HERO-RT
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Multicenter, Single-Arm, Prospective Phase II Clinical Study of Trastuzumab Rezetecan Combined with Radiotherapy in Patients with HER2-Mutated Oligoprogressive Advanced Non-Small Cell Lung Cancer

Conditions

HER2-mutated Advanced Non-small Cell Lung Cancer With Oligoprogression

Keywords

HER2-mutated; oligoprogression

Outcome Measures

Primary Outcomes (1)

• Safety (incidence of Grade ≥3 interstitial lung disease)

  from the first dose administration to the end of safety follow-up after study discontinuation

  up to 12 months

Secondary Outcomes (5)

• Progression-free survival， PFS

  up to 12 months

• Overall response rate, ORR

  up to 12 months

• Disease control rate, DCR

  up to 12 months

• duration of response, DoR

  up to 12 months

• Overall survival, OS

  up to 12 months

Study Arms (1)

Experimental

EXPERIMENTAL

Trastuzumab Rezetecan combined with radiotherapy

Drug: Trastuzumab Rezetecan combined with radiotherapy

Interventions

Trastuzumab Rezetecan combined with radiotherapy DRUG

Trastuzumab Rezetecan administered intravenously at a dose of 4.8 mg/kg Q3W until disease progression or intolerable toxicity occurs. Radiotherapy: Radiotherapy targeting oligoprogressive lesions is recommended to be completed within Cycle 1 or prior to Cycle 2 of Trastuzumab Rezetecan treatment. Radiotherapy shall adopt organ- and risk-adapted fractionation regimens with curative radiotherapy dose as the principle; high biological effective dose (BED) regimens capable of achieving durable local control are preferred. Stereotactic body radiation therapy (SBRT) may be prioritized for peripheral pulmonary, adrenal, hepatic and other lesions. Risk-adapted multifraction regimens will be applied to lesions located in the central thorax, mediastinal lymph nodes, spine and regions adjacent to critical organs at risk. The specific radiation dose will be determined comprehensively based on lesion location, size, distance to organs at risk and previous radiotherapy history.

Experimental

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 and ≤75 years, male or female.
• Confirmed HER2 mutation (detected by PCR or NGS). Patients developed oligoprogression after achieving tumor response following prior systemic therapy for advanced NSCLC (CR/PR/SD lasting ≥6 months).
• Note: The number of prior lines of systemic therapy is limited to ≤2 lines. Prior regimens may include platinum-based chemotherapy, chemoimmunotherapy, chemoimmunotherapy combined with anti-angiogenic therapy, HER2-TKIs, or Trastuzumab Rezetecan; however, patients must have received at least one line of platinum-based chemotherapy.
• Meet the definition of oligoprogression: under continuous systemic therapy, only 1-5 extracranial lesions progress, the number of organs involved by progressive lesions ≤3.
• All oligoprogressive lesions planned for radiotherapy are extracranial and amenable to safely delivered fractionated radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Expected survival ≥3 months.
• At least one measurable lesion outside the planned radiation field at baseline per RECIST Version 1.1, to serve as target lesion for systemic efficacy evaluation.
• Pulmonary function: FEV₁ \>70% of predicted value.
• Adequate function of major organs meeting the criteria below:
• Hematology tests (no blood transfusion, granulocyte colony-stimulating factor (G-CSF) or other hematopoietic stimulating factors administered within 14 days prior to the first study treatment):
• Hemoglobin (Hb) ≥90 g/L; Platelet count (PLT) ≥100×10⁹/L; Absolute neutrophil count (ANC) ≥1.5×10⁹/L; White blood cell count (WBC) ≥3.0×10⁹/L.
• Biochemistry tests: Liver function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN; for patients with liver metastases, ALT and AST ≤5 × ULN. Total serum bilirubin (TBIL) ≤1.5 × ULN (for patients with confirmed Gilbert's syndrome, total bilirubin ≤3.0 mg/dL).
• Renal function: Serum creatinine ≤1.5 × ULN OR creatinine clearance rate (CrCl) ≥50 mL/min (calculated using the Cockcroft-Gault formula). Urine protein \<2+ on dipstick. If urine protein ≥2+, additional 24-hour quantitative urine protein test is required; subjects with 24-hour urine protein \<1 g are eligible for enrollment.
• Coagulation function: Activated partial thromboplastin time (APTT), international normalized ratio (INR) and prothrombin time (PT) ≤1.5 × ULN.

You may not qualify if:

• Presence of EGFR sensitizing mutations (Exon 19 deletion / Exon 21 L858R), 2.ALK rearrangements, positive ROS1/RET fusions, MET exon 14 skipping mutations, or KRAS G12C mutations.
• Uncontrolled or severe cardiovascular diseases, such as severe/unstable angina, symptomatic congestive heart failure (NYHA Class II-IV), myocardial infarction within 6 months prior to the first study treatment, or unstable angina or unstable arrhythmia occurring within 1 month before initiation of study treatment.
• Active central nervous system (CNS) tumor metastases. Subjects with a history of leptomeningeal metastasis or current leptomeningeal metastasis are excluded. Exception: Subjects with CNS metastases who have received adequate local therapy (surgery or radiotherapy) at least 2 weeks prior to the first dose, do not require steroid therapy, have neurologically recovered to baseline (excluding residual signs/symptoms related to CNS treatment), and whose brain lesions are not oligoprogressive lesions in this study may be enrolled.
• Presence of pleural effusion, ascites or pericardial effusion requiring intervention within 7 days before the first dose.
• Receipt of extensive-field radiotherapy within the past 4 weeks, or anticipated overlap with the radiotherapy field in this study where organ risk constraints cannot be satisfied.
• Toxicities and/or complications from prior interventions that have not recovered to NCI-CTCAE Grade ≤1. Exception: Subjects may be enrolled if the investigator judges that adverse events are NCI-CTCAE Grade ≤2 and pose no safety risks. Subjects previously treated with immune checkpoint inhibitors with stable Type 1 diabetes or hypothyroidism under hormone replacement therapy are eligible.
• Receipt of strong/moderate CYP3A4 inhibitors or strong/moderate CYP3A4 inducers within the shorter of either 3 drug half-lives or 14 days prior to the first dose.
• Subjects with known or suspected interstitial lung disease; moderate to severe pulmonary diseases that may interfere with detection or management of drug-related pulmonary toxicity and severely impair respiratory function within 3 months before the first dose, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans, pulmonary embolism, severe asthma, severe COPD, severe obstructive/restrictive ventilatory dysfunction; any autoimmune, connective tissue or inflammatory diseases involving the lungs (e.g., rheumatoid arthritis, sicca syndrome, sarcoidosis), or history of prior pneumonectomy. Subjects who developed Grade ≥3 interstitial lung disease during previous immune checkpoint inhibitor treatment are excluded.
• Other concurrent malignant tumors diagnosed within ≤3 years prior to the first dose, except for adequately treated papillary thyroid carcinoma, cervical carcinoma in situ, basal cell or squamous cell skin cancer, locally confined prostate cancer after radical resection, and ductal carcinoma in situ after radical resection (hormonal therapy for non-metastatic prostate or breast cancer is permitted).
• Severe infection within 4 weeks prior to the first dose, including but not limited to bacteremia requiring hospitalization, severe pneumonia; active infection of CTCAE Grade ≥2 requiring systemic antibiotic therapy within 2 weeks prior to the first dose.
• Active hepatitis B or hepatitis C infection. Subjects positive for HBsAg or HBc Ab may participate if HBV DNA is below the upper limit of normal (ULN) of the local study laboratory; if no ULN is available at the site, HBV DNA must be \<1000 copies/mL or 500 IU/mL. Subjects positive for anti-HCV antibody may participate if HCV RNA is below the ULN of the local study laboratory.
• History of active pulmonary tuberculosis infection within 1 year before enrollment confirmed by medical history or CT scan; or history of active pulmonary tuberculosis infection more than 1 year previously without standardized treatment.
• History of immunodeficiency, including positive HIV serology or history of organ transplantation.
• Major surgery within 28 days prior to the first dose (excluding diagnostic surgery), or planned major surgery during the study period (excluding diagnostic surgery).
• Administration of live attenuated vaccines within 28 days before the first dose, or planned administration of live attenuated vaccines during the study.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

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MeSH Terms

Interventions

Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Xiao rong XR Dong

CONTACT

13986252286; xiaorongdong@hust.edu.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: Professor

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: August 24, 2026
• Study Start: August 30, 2026
• Primary Completion (Estimated): August 30, 2029
• Study Completion (Estimated): August 30, 2029
• Last Updated: August 24, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share