HER2-mutated Advanced Non-small Cell Lung Cancer With OligoprogressionPhase 2NCT07781202

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

A Phase 2 study testing Trastuzumab Rezetecan combined with radiotherapy in people with HER2-mutated Advanced Non-small Cell Lung Cancer With Oligoprogression, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial 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 Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: HER2-mutated Advanced Non-small Cell Lung Cancer With Oligoprogression
What is being tested?: Trastuzumab Rezetecan combined with radiotherapy
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: No sites listed yet
Study dates: 30 Aug 2026to 30 Aug 2029
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.
Evaluated by Doppler echocardiography: Left ventricular ejection fraction (LVEF) ≥50%. Electrocardiogram basically normal; QTcF <450 ms for males and <470 ms for females.
Non-surgically sterile women of childbearing potential and male subjects must agree to use at least one medically accepted contraceptive method (e.g., intrauterine device, oral contraceptives, condoms) throughout study treatment and for 6 months after completion of study treatment. Non-surgically sterile women of childbearing potential must have a negative serum HCG test within 7 days before the first dose.
Subjects voluntarily participate in this study, sign the informed consent form, demonstrate good compliance and are willing to complete follow-up visits.

Who cannot join

1.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.
3.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.
4.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.
5.Presence of pleural effusion, ascites or pericardial effusion requiring intervention within 7 days before the first dose.
6.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.
7.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.

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8.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.
9.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.
10.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).
11.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.
12.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.
13.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.
14.History of immunodeficiency, including positive HIV serology or history of organ transplantation.
15.Major surgery within 28 days prior to the first dose (excluding diagnostic surgery), or planned major surgery during the study period (excluding diagnostic surgery).
16.Administration of live attenuated vaccines within 28 days before the first dose, or planned administration of live attenuated vaccines during the study.
17.Known history of severe allergic reaction to any component of trastuzumab rezetecan or radiotherapy.
18.Known psychiatric disorders, alcohol abuse, drug addiction or substance abuse.
19.Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study period.
20.Any other conditions that, in the investigator's judgment, may increase risks associated with study participation, interfere with study outcomes, or render the subject unsuitable for enrollment.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Xiao rong XR Dong contact

13986252286

xiaorongdong@hust.edu.cn

About this study

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

Read the detailed description

This is a multicenter, single-arm, prospective Phase II clinical study aiming to evaluate the efficacy and safety of Trastuzumab Rezetecan combined with radiotherapy in patients with HER2-mutated advanced non-small cell lung cancer with oligoprogression. A total of 30 subjects are planned to be enrolled. Eligible patients are those with HER2-mutated advanced non-small cell lung cancer who obtained clinical benefit following prior systemic therapy and subsequently developed oligoprogression.

Subjects meeting the eligibility criteria after screening will receive the following treatment: 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.

Conditions: HER2-mutated Advanced Non-small Cell Lung Cancer With Oligoprogression
Being tested: Trastuzumab Rezetecan combined with radiotherapy
Keywords: HER2-mutated, oligoprogression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Trastuzumab Rezetecan combined with radiotherapyDrug
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.

Study groups in NCT07781202
Study group	Role	What they receive
Experimental	Experimental	Trastuzumab Rezetecan combined with radiotherapy Receives: Drug: Trastuzumab Rezetecan combined with radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety (incidence of Grade ≥3 interstitial lung disease)
from the first dose administration to the end of safety follow-up after study discontinuation
Measured: up to 12 months

Secondary outcomes (5)

Progression-free survival， PFS
PFS is defined as the time elapsed between the start of treatment and the first sign of disease progression or death from any cause.
Measured: up to 12 months
Overall response rate, ORR
Defined as the proportion of patients whose tumor volume reduction meets the predefined threshold (CR/PR) and lasts for the minimum required duration according to recognized response evaluation criteria (e.g., RECIST Version 1.1 for solid tumors).
Measured: up to 12 months
Disease control rate, DCR
Number of cases with completed/partial response and stable disease after treatment as a percentage of evaluable cases.
Measured: up to 12 months
duration of response, DoR
Defined as the time interval from the first documented assessment of complete response (CR) or partial response (PR) to the first documented assessment of progressive disease (PD) or death due to any cause
Measured: up to 12 months
Overall survival, OS
OS is defined as the time elapsed between the initiation of treatment and mortality from any cause
Measured: up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Aug 202630 Aug 2029

First posted24 Aug 2026
Study start30 Aug 2026 (estimated)
Primary completion30 Aug 2029 (estimated)
Study completion30 Aug 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (23)Papers the sponsor has linked to this study.
Other trials for HER2-mutated Advanced Non-small Cell Lung Cancer With OligoprogressionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07781202
Sponsor's protocol ID: HERO-RT
Status last verified: Aug 2026
First submitted: 17 Aug 2026
Last updated: 24 Aug 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: There is no plan to make individual participant data (IPD) available to other researchers.

Publications

Khatri VM, Mestres-Villanueva MA, Yarlagadda S, Doniparthi A, Smith DB, Nakashima JY, Bryant JM, Zhao D, Upadhyay R, Mills MN, Oliver DE, Yu HM, Palmer JD, Williams NO, Mahtani RL, Ahluwalia MS, Soliman HH, Han HS, Soyano AE, Kim Y, Kotecha R, Beyer SJ, Ahmed KA. Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases. NPJ Breast Cancer. 2024 Nov 21;10(1):100. doi: 10.1038/s41523-024-00711-w.
PubMed 39572568
Dingemans AC, Hendriks LEL, Berghmans T, Levy A, Hasan B, Faivre-Finn C, Giaj-Levra M, Giaj-Levra N, Girard N, Greillier L, Lantuejoul S, Edwards J, O'Brien M, Reck M, Smit EF, Van Schil P, Postmus PE, Ramella S, Lievens Y, Gaga M, Peled N, Scagliotti GV, Senan S, Paz-Ares L, Guckenberger M, McDonald F, Ekman S, Cufer T, Gietema H, Infante M, Dziadziuszko R, Peters S, Porta RR, Vansteenkiste J, Dooms C, de Ruysscher D, Besse B, Novello S. Definition of Synchronous Oligometastatic Non-Small Cell Lung Cancer-A Consensus Report. J Thorac Oncol. 2019 Dec;14(12):2109-2119. doi: 10.1016/j.jtho.2019.07.025. Epub 2019 Aug 6.
PubMed 31398540
Lebow ES, Pike LRG, Seidman AD, Moss N, Beal K, Yu Y. Symptomatic Necrosis With Antibody-Drug Conjugates and Concurrent Stereotactic Radiotherapy for Brain Metastases. JAMA Oncol. 2023 Dec 1;9(12):1729-1733. doi: 10.1001/jamaoncol.2023.4492.
PubMed 37883079
Loap P, Chabli S, Cottu P, Kirova Y. Safety and Tolerability of Concurrent Radiotherapy and Sacituzumab Govitecan in Metastatic Breast Cancer. Am J Clin Oncol. 2025 Aug 1;48(8):399-402. doi: 10.1097/COC.0000000000001195. Epub 2025 Apr 3.
PubMed 40178882
Debbi K, Benderra MA, Medioni J, Durdux C, To NH, Boukhobza C, Grellier N, Benmaziane A, Monnier L, Gligorov J, Assaf E, Belkacemi Y. Safety and efficacy of combined trastuzumab-deruxtecan and concurrent radiation therapy in breast cancer. The TENDANCE multicentric French study. Breast. 2025 Apr;80:104421. doi: 10.1016/j.breast.2025.104421. Epub 2025 Feb 13.
PubMed 39983437
Stumpf PK, Cittelly DM, Robin TP, Carlson JA, Stuhr KA, Contreras-Zarate MJ, Lai S, Ormond DR, Rusthoven CG, Gaspar LE, Rabinovitch R, Kavanagh BD, Liu A, Diamond JR, Kabos P, Fisher CM. Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4. Clin Cancer Res. 2019 Jul 1;25(13):3946-3953. doi: 10.1158/1078-0432.CCR-18-2851. Epub 2019 Apr 2.
PubMed 30940654
Salvestrini V, Kim K, Caini S, Alkner S, Ekholm M, Skytta T, Becherini C, Coles CE, Kaidar-Person O, Offersen B, de Azambuja E, Visani L, Cortes J, Harbeck N, Rugo HS, Isacke CM, Marangoni E, Morandi A, Lambertini M, Poortmans P, Livi L, Meattini I. Safety profile of trastuzumab-emtansine (T-DM1) with concurrent radiation therapy: A systematic review and meta-analysis. Radiother Oncol. 2023 Sep;186:109805. doi: 10.1016/j.radonc.2023.109805. Epub 2023 Jul 10.
PubMed 37437610
Natangelo S, Trapani D, Koukoutzeli C, Boscolo Bielo L, Marvaso G, Jereczek-Fossa BA, Curigliano G. Radiation therapy, tissue radiosensitization, and potential synergism in the era of novel antibody-drug conjugates. Crit Rev Oncol Hematol. 2024 Mar;195:104270. doi: 10.1016/j.critrevonc.2024.104270. Epub 2024 Jan 24.
PubMed 38272150
Li Z, Wang Y, Sun Y, Wang L, Li X, Sun L, He Z, Yang H, Wang Y, Wang Q, Song Z, Hong W, Wang Y, Xia G, Yu Y, Peng M, Song Y, Wang D, Meng R, Fang J, Luo Y, Liang W, Hu S, Wang Z, Song K, Li Y, Yang L, Shi W, Lu S. Trastuzumab rezetecan, a HER2-directed antibody-drug conjugate, in patients with advanced HER2-mutant non-small-cell lung cancer (HORIZON-Lung): phase 2 results from a multicentre, single-arm study. Lancet Oncol. 2025 Apr;26(4):437-446. doi: 10.1016/S1470-2045(25)00012-9. Epub 2025 Feb 25.
PubMed 40020696
Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazieres J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Perol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Janne PA; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251. doi: 10.1056/NEJMoa2112431. Epub 2021 Sep 18.
PubMed 34534430
Iwasaka-Neder J, Bedoya MA, Connors J, Warfield S, Bixby SD. Morphometric and clinical comparison of MRI-based synthetic CT to conventional CT of the hip in children. Pediatr Radiol. 2024 May;54(5):743-757. doi: 10.1007/s00247-024-05888-7. Epub 2024 Feb 29.
PubMed 38421417
Tsai CJ, Yang JT, Shaverdian N, Patel J, Shepherd AF, Eng J, Guttmann D, Yeh R, Gelblum DY, Namakydoust A, Preeshagul I, Modi S, Seidman A, Traina T, Drullinsky P, Flynn J, Zhang Z, Rimner A, Gillespie EF, Gomez DR, Lee NY, Berger M, Robson ME, Reis-Filho JS, Riaz N, Rudin CM, Powell SN; CURB Study Group. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet. 2024 Jan 13;403(10422):171-182. doi: 10.1016/S0140-6736(23)01857-3. Epub 2023 Dec 14.
PubMed 38104577
Wang Z, Wei L, Li J, Zhou H, Li S, Chen D, Yu Y, Zhao L, Zhu X, Song Y. Combing stereotactic body radiotherapy with checkpoint inhibitors after oligoprogression in advanced non-small cell lung cancer. Transl Lung Cancer Res. 2021 Dec;10(12):4368-4379. doi: 10.21037/tlcr-21-682.
PubMed 35070747
He J, Zhou H, Xiong J, Huang Y, Huang N, Jiang J. Association between elevated homocysteine levels and obstructive sleep apnea hypopnea syndrome: a systematic review and updated meta-analysis. Front Endocrinol (Lausanne). 2024 Jun 3;15:1378293. doi: 10.3389/fendo.2024.1378293. eCollection 2024.
PubMed 38887264
Shun Lu, 2022WCLC,OA11.05

Study at a glance

From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT07781202
Acronym / sponsor ID: HERO-RT
Conditions: HER2-mutated Advanced Non-small Cell Lung Cancer With Oligoprogression
Keywords: HER2-mutated, oligoprogression
Phase: Phase 2
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 30 participants (estimated)
Lead sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
Study start: 30 Aug 2026 (estimated)
Primary completion: 30 Aug 2029 (estimated)
Study completion: 30 Aug 2029 (estimated)
First posted: 24 Aug 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Experimental	Experimental	Drug: Trastuzumab Rezetecan combined with radiotherapyTrastuzumab Rezetecan combined with radiotherapy

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (18 listed)

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.

Key exclusion criteria (19 listed)

1.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.
3.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.
4.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.
5.Presence of pleural effusion, ascites or pericardial effusion requiring intervention within 7 days before the first dose.
6.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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Trastuzumab Rezetecan combined with radiotherapyTrastuzumab 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.	Drug	Experimental

Primary outcome

Safety (incidence of Grade ≥3 interstitial lung disease)
Time frame: up to 12 months
from the first dose administration to the end of safety follow-up after study discontinuation

5 secondary outcomes

Progression-free survival， PFS
Time frame: up to 12 months
Overall response rate, ORR
Time frame: up to 12 months
Disease control rate, DCR
Time frame: up to 12 months
duration of response, DoR
Time frame: up to 12 months
Overall survival, OS
Time frame: up to 12 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
Background: PubMed 39572568Khatri VM, Mestres-Villanueva MA, Yarlagadda S, Doniparthi A, Smith DB, Nakashima JY, Bryant JM, Zhao D, Upadhyay R, Mills MN, Oliver DE, Yu HM, Palmer JD, Williams NO, Mahtani RL, Ahluwalia MS, Soliman HH, Han HS, Soyano AE, Kim Y, Kotecha R, Beyer SJ, Ahmed KA. Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases. NPJ Breast Cancer. 2024 Nov 21;10(1):100. doi: 10.1038/s41523-024-00711-w.
Background: PubMed 31398540Dingemans AC, Hendriks LEL, Berghmans T, Levy A, Hasan B, Faivre-Finn C, Giaj-Levra M, Giaj-Levra N, Girard N, Greillier L, Lantuejoul S, Edwards J, O'Brien M, Reck M, Smit EF, Van Schil P, Postmus PE, Ramella S, Lievens Y, Gaga M, Peled N, Scagliotti GV, Senan S, Paz-Ares L, Guckenberger M, McDonald F, Ekman S, Cufer T, Gietema H, Infante M, Dziadziuszko R, Peters S, Porta RR, Vansteenkiste J, Dooms C, de Ruysscher D, Besse B, Novello S. Definition of Synchronous Oligometastatic Non-Small Cell Lung Cancer-A Consensus Report. J Thorac Oncol. 2019 Dec;14(12):2109-2119. doi: 10.1016/j.jtho.2019.07.025. Epub 2019 Aug 6.
Results publication: PubMed 37883079Lebow ES, Pike LRG, Seidman AD, Moss N, Beal K, Yu Y. Symptomatic Necrosis With Antibody-Drug Conjugates and Concurrent Stereotactic Radiotherapy for Brain Metastases. JAMA Oncol. 2023 Dec 1;9(12):1729-1733. doi: 10.1001/jamaoncol.2023.4492.
Results publication: PubMed 40178882Loap P, Chabli S, Cottu P, Kirova Y. Safety and Tolerability of Concurrent Radiotherapy and Sacituzumab Govitecan in Metastatic Breast Cancer. Am J Clin Oncol. 2025 Aug 1;48(8):399-402. doi: 10.1097/COC.0000000000001195. Epub 2025 Apr 3.
Results publication: PubMed 39983437Debbi K, Benderra MA, Medioni J, Durdux C, To NH, Boukhobza C, Grellier N, Benmaziane A, Monnier L, Gligorov J, Assaf E, Belkacemi Y. Safety and efficacy of combined trastuzumab-deruxtecan and concurrent radiation therapy in breast cancer. The TENDANCE multicentric French study. Breast. 2025 Apr;80:104421. doi: 10.1016/j.breast.2025.104421. Epub 2025 Feb 13.
Results publication: PubMed 30940654Stumpf PK, Cittelly DM, Robin TP, Carlson JA, Stuhr KA, Contreras-Zarate MJ, Lai S, Ormond DR, Rusthoven CG, Gaspar LE, Rabinovitch R, Kavanagh BD, Liu A, Diamond JR, Kabos P, Fisher CM. Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4. Clin Cancer Res. 2019 Jul 1;25(13):3946-3953. doi: 10.1158/1078-0432.CCR-18-2851. Epub 2019 Apr 2.
Results publication: PubMed 37437610Salvestrini V, Kim K, Caini S, Alkner S, Ekholm M, Skytta T, Becherini C, Coles CE, Kaidar-Person O, Offersen B, de Azambuja E, Visani L, Cortes J, Harbeck N, Rugo HS, Isacke CM, Marangoni E, Morandi A, Lambertini M, Poortmans P, Livi L, Meattini I. Safety profile of trastuzumab-emtansine (T-DM1) with concurrent radiation therapy: A systematic review and meta-analysis. Radiother Oncol. 2023 Sep;186:109805. doi: 10.1016/j.radonc.2023.109805. Epub 2023 Jul 10.
Results publication: PubMed 38272150Natangelo S, Trapani D, Koukoutzeli C, Boscolo Bielo L, Marvaso G, Jereczek-Fossa BA, Curigliano G. Radiation therapy, tissue radiosensitization, and potential synergism in the era of novel antibody-drug conjugates. Crit Rev Oncol Hematol. 2024 Mar;195:104270. doi: 10.1016/j.critrevonc.2024.104270. Epub 2024 Jan 24.
Results publication: PubMed 40020696Li Z, Wang Y, Sun Y, Wang L, Li X, Sun L, He Z, Yang H, Wang Y, Wang Q, Song Z, Hong W, Wang Y, Xia G, Yu Y, Peng M, Song Y, Wang D, Meng R, Fang J, Luo Y, Liang W, Hu S, Wang Z, Song K, Li Y, Yang L, Shi W, Lu S. Trastuzumab rezetecan, a HER2-directed antibody-drug conjugate, in patients with advanced HER2-mutant non-small-cell lung cancer (HORIZON-Lung): phase 2 results from a multicentre, single-arm study. Lancet Oncol. 2025 Apr;26(4):437-446. doi: 10.1016/S1470-2045(25)00012-9. Epub 2025 Feb 25.
Results publication: PubMed 34534430Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazieres J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Perol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Janne PA; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251. doi: 10.1056/NEJMoa2112431. Epub 2021 Sep 18.
Results publication: PubMed 38421417Iwasaka-Neder J, Bedoya MA, Connors J, Warfield S, Bixby SD. Morphometric and clinical comparison of MRI-based synthetic CT to conventional CT of the hip in children. Pediatr Radiol. 2024 May;54(5):743-757. doi: 10.1007/s00247-024-05888-7. Epub 2024 Feb 29.
Results publication: PubMed 38104577Tsai CJ, Yang JT, Shaverdian N, Patel J, Shepherd AF, Eng J, Guttmann D, Yeh R, Gelblum DY, Namakydoust A, Preeshagul I, Modi S, Seidman A, Traina T, Drullinsky P, Flynn J, Zhang Z, Rimner A, Gillespie EF, Gomez DR, Lee NY, Berger M, Robson ME, Reis-Filho JS, Riaz N, Rudin CM, Powell SN; CURB Study Group. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet. 2024 Jan 13;403(10422):171-182. doi: 10.1016/S0140-6736(23)01857-3. Epub 2023 Dec 14.
Individual participant dataSharing planned: No. There is no plan to make individual participant data (IPD) available to other researchers.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Xiao rong XR Dong contact

13986252286

xiaorongdong@hust.edu.cn

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xiao rong XR Dong (13986252286, xiaorongdong@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety (incidence of Grade ≥3 interstitial lung disease) (time frame: up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07781202, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.