Efficacy and Safety of SBRT Combined With Becotatug Vedotin (MRG003) in EGFR-Positive Metastatic Tumor Patients With Oligometastases

NCT07481799 | Recruiting Phase 3

• 1 other identifier: ZDWY.FSZLK.008
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

The combination of local consolidative therapy for oligometastases with systemic therapy offers the potential for clinical cure and significantly prolongs survival in a subset of patients with advanced metastatic disease. However, a considerable proportion of patients still do not benefit from this approach. Becotatug vedotin (MRG003) is an antibody-drug conjugate that carries the payload monomethyl auristatin E (MMAE), a microtubule inhibitor. MMAE has been shown to effectively enhance radiosensitivity in various preclinical tumor models, including head and neck squamous cell carcinoma, liver cancer, gastric cancer, pancreatic cancer, and lung cancer. Furthermore, multiple clinical studies have demonstrated the promising therapeutic potential of vicetuximab in EGFR-positive solid tumors. Based on this background, we plan to conduct a clinical study evaluating the combination of stereotactic body radiotherapy (SBRT) for oligometastases with investigator-selected systemic therapy and Becotatug vedotin (MRG003) in patients with EGFR-positive oligometastatic tumors.

Conditions

Oligo-metastatic Cancer

Keywords

EGFR-postive oligo-metastatic cancer; SBRT; MMAE; Becotatug vedotin

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Defined as time from randomization to loco-regional or distant metastasis relapse or death from any cause, whichever occurred first.

  1 year

Secondary Outcomes (7)

• Overall Survival (OS)

  1 year

• Objective Response Rate (ORR)

  3 months after SBRT

• Disease Control Rate (DCR)

  3 months after SBRT

• Duration of Response (DoR)

  1 year

• Health related quality of Life

  Baseline, after every two cycles of systemic therapy, before SBRT, after SBRT, and at each follow-up.

Study Arms (2)

Becotatug vedotin plus SBRT and systemic therapy arm

EXPERIMENTAL

For patients in the experimental group receives Becotatug vedotin plus SBRT and systemic therapy.

Drug: Becotatug Vedotin; Radiation: SBRT; Drug: Systemic Therapy/Standard of Care

SBRT and systemic therapy arm

ACTIVE COMPARATOR

For patients in the control group receives SBRT and systemic therapy.

Radiation: SBRT; Drug: Systemic Therapy/Standard of Care

Interventions

Becotatug Vedotin DRUG

Becotatug vedotin was administered intravenously at a dose of 2.0 mg/kg every 3 weeks (Q3W).

Becotatug vedotin plus SBRT and systemic therapy arm

SBRT RADIATION

All oligometastatic lesions will be treated with SBRT with curative intent. Radiation doses are determined based on published clinical studies

Becotatug vedotin plus SBRT and systemic therapy arm; SBRT and systemic therapy arm

Systemic Therapy/Standard of Care DRUG

Systemic therapy /Standard of Care will be determined at the investigator's discretion, in accordance with clinical guidelines and individual patient characteristics.

Becotatug vedotin plus SBRT and systemic therapy arm; SBRT and systemic therapy arm

Eligibility Criteria

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

You may qualify if:

• Age: 18 to 75 years (inclusive), male or female.
• Patients with histologically or cytologically confirmed recurrent or metastatic solid tumors who are not amenable to curative surgery.
• Oligometastatic lesions detected on imaging (biopsy of metastatic tissue is preferred but not mandatory). The total number of metastatic lesions must be \<=5.
• The primary tumor has been treated radically and is controlled.
• Subjects must provide tumor tissue samples for EGFR testing of the primary tumor or metastatic lesions:
• a) Sample requirements: Neutral formalin-fixed, paraffin-embedded (FFPE) tissue blocks or 10 unstained tumor tissue or cytology slides. Both fresh and archival samples are acceptable, with fresh samples preferred. Subjects unable to provide freshly obtained tissue may provide archival tumor tissue samples collected within 2 years prior to informed consent. For subjects unable to provide tumor tissue samples meeting the above requirements, enrollment is subject to confirmation after discussion with the Sponsor.
• All metastatic lesions are deemed amenable to SBRT (Stereotactic Body Radiation Therapy) by multidisciplinary team (MDT) consultation.
• For patients whose metastatic lesions have received prior local therapy (e.g., surgery, radiofrequency ablation, radiotherapy):
• If the treated metastatic lesion is controlled on imaging, the patient is eligible, and SBRT is not required for that specific site.
• If the treated metastatic lesion is not controlled on imaging:
• If the prior therapy was surgery and the site is amenable to SBRT, the patient is eligible;
• If the prior therapy was radiotherapy or RFA, the patient is ineligible.
• Maximum diameter of brain metastases \<= 3 cm.
• Maximum diameter of extra-cranial metastases \<= 5 cm.
• a) For bone metastases, the criterion may be extended to a maximum diameter of 6 cm (e.g., ribs, scapula, pelvis) if the investigator deems treatment safe.

You may not qualify if:

• History of severe hypersensitivity to any component of monoclonal antibodies.
• The investigator's choice of systemic therapy regimen contains taxanes (or other microtubule inhibitors) .
• Severe infection within 4 weeks prior to the start of study treatment; or active infection of CTCAE Grade\>=2 requiring systemic antibiotic treatment within 2 weeks prior to the first dose.
• Received anti-tumor therapy such as chemotherapy, biotherapy, targeted therapy, immunotherapy, or other investigational drugs within 4 weeks prior to the first dose of study drug or investigator's choice of systemic therapy and SBRT; Exceptions:
• The interval between the last dose of oral fluorouracil or small molecule targeted drugs and the first dose of study treatment is \> 2 weeks or 5 half-lives (whichever is shorter);
• The interval between the last dose of Traditional Chinese Medicine (TCM) with anti-tumor indications and the first dose of study treatment is \> 2 weeks;
• The interval between the completion of prior radioactive seed implantation and the first dose of study treatment is \> 4 weeks or 5 half-lives of the seeds (whichever is shorter); the interval between the completion of Tumor Treating Fields and the first dose of study treatment is \< 7 days.
• Received treatment with strong CYP3A4 or CYP2D6 inhibitors or inducers, or P-gp inhibitors within 5 half-lives prior to the first dose.
• Prior treatment with EGFR ADCs, or prior treatment with ADCs containing microtubule inhibitors.
• History of interstitial lung disease, such as idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or radiation pneumonitis requiring steroid treatment; or imaging at screening suggests suspected ILD or ILD cannot be excluded (subjects with radiation pneumonitis limited solely to the radiation field may participate); or presence of respiratory failure, severe asthma, severe chronic obstructive pulmonary disease (COPD), or other pulmonary diseases severely affecting lung function; or prior pneumonectomy.
• Clinical or radiological evidence of spinal cord compression, or tumor distance to the spinal cord \< 3 mm.
• Grade \>= 2 coronary heart disease, arrhythmia (including QTc interval prolongation \> 450 ms for males, \> 470 ms for females), or cardiac insufficiency.
• Patients with brain metastases requiring surgical decompression.
• Patients with malignant effusions.
• patients with concomitant malignancies.

Sponsors & Collaborators

• Ming-Yuan Chen: lead

Study Sites (2)

The Fifth Affiliated Hospital,Sun Yat-sen University

Zhuhai, Guangdong, 519099, China

NOT YET RECRUITING

The Fifth Affiliated Hospital,Sun Yat-sen University

Zhuhai, Guangdong, 519099, China

RECRUITING

MeSH Terms

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Mingyuan Chen

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mingyuan Chen

CONTACT

+86 18124188280; chmingy@mail.sysu.edu.cn

Xiaoting Cai

CONTACT

+86 15602268126; caixiaoting17@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Chief physician

Study Record Dates

• First Submitted: March 15, 2026
• First Posted: March 19, 2026
• Study Start: February 6, 2026
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2030
• Last Updated: April 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)