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

Phase 3 Clinical Study on the Efficacy and Safety of SBRT Combined With Becotatug Vedotin (MRG003) in EGFR-Positive Metastatic Tumor Patients With Oligometastases

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.

Study Overview

• Status: Recruiting
• Conditions: Oligo-metastatic Cancer
• Intervention / Treatment: Drug: Becotatug Vedotin; Radiation: SBRT; Drug: Systemic Therapy/Standard of Care

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mingyuan Chen; Phone Number: +86 18124188280; Email: chmingy@mail.sysu.edu.cn
• Study Contact Backup: Name: Xiaoting Cai; Phone Number: +86 15602268126; Email: caixiaoting17@163.com

Study Locations

• China
  • Guangdong
    • Zhuhai, Guangdong, China, 519099
      • Not yet recruiting
      • The Fifth Affiliated Hospital,Sun Yat-sen University
      • Contact: Rui You; Phone Number: 13580439820; Email: your5@mail.sysu.edu.cn
    • Zhuhai, Guangdong, China, 519099
      • Recruiting
      • The Fifth Affiliated Hospital,Sun Yat-sen University
      • Contact: You Rui; Phone Number: 13580439820; Email: your5@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18 to 75 years (inclusive), male or female.
2. Patients with histologically or cytologically confirmed recurrent or metastatic solid tumors who are not amenable to curative surgery.
3. Oligometastatic lesions detected on imaging (biopsy of metastatic tissue is preferred but not mandatory). The total number of metastatic lesions must be <=5.
4. The primary tumor has been treated radically and is controlled.

5. 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.

6. All metastatic lesions are deemed amenable to SBRT (Stereotactic Body Radiation Therapy) by multidisciplinary team (MDT) consultation.

7. For patients whose metastatic lesions have received prior local therapy (e.g., surgery, radiofrequency ablation, radiotherapy):

   1. If the treated metastatic lesion is controlled on imaging, the patient is eligible, and SBRT is not required for that specific site.

   2. If the treated metastatic lesion is not controlled on imaging:

      1. If the prior therapy was surgery and the site is amenable to SBRT, the patient is eligible;
      2. If the prior therapy was radiotherapy or RFA, the patient is ineligible.
8. Maximum diameter of brain metastases <= 3 cm.

9. 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.

10. ECOG performance status of 0-1.
11. Life expectancy >= 6 months.

Exclusion Criteria:

1. History of severe hypersensitivity to any component of monoclonal antibodies.
2. The investigator's choice of systemic therapy regimen contains taxanes (or other microtubule inhibitors) .
3. 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.

4. 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:

   1. 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);
   2. 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;
   3. 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.
5. Received treatment with strong CYP3A4 or CYP2D6 inhibitors or inducers, or P-gp inhibitors within 5 half-lives prior to the first dose.
6. Prior treatment with EGFR ADCs, or prior treatment with ADCs containing microtubule inhibitors.
7. 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.
8. Clinical or radiological evidence of spinal cord compression, or tumor distance to the spinal cord < 3 mm.
9. Grade >= 2 coronary heart disease, arrhythmia (including QTc interval prolongation > 450 ms for males, > 470 ms for females), or cardiac insufficiency.
10. Patients with brain metastases requiring surgical decompression.
11. Patients with malignant effusions.
12. patients with concomitant malignancies.
13. Dementia or seizures.
14. Comorbidities requiring chronic use of immunosuppressive medication, or systemic or local corticosteroids at immunosuppressive doses, or receipt of high-dose corticosteroids within 4 weeks prior to enrollment.
15. Active pulmonary tuberculosis, currently undergoing anti-tuberculosis treatment, or having received such treatment within 1 year prior to screening.
16. Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonitis, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism). Patients with vitiligo or childhood asthma that has completely resolved without need for intervention in adulthood are eligible; patients with asthma requiring bronchodilators for medical intervention are excluded.
17. HIV positive; HBsAg positive with detectable HBV DNA >= 1000 copies/ml); positive blood screening for chronic Hepatitis C (HCV antibody positive). Vaccination with any anti-infective vaccine (e.g., influenza, varicella) within 4 weeks prior to enrollment.
18. Positive pregnancy test in women of childbearing potential, or breastfeeding women.
19. Other patients considered unsuitable for inclusion by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Becotatug vedotin plus SBRT and systemic therapy arm; For patients in the experimental group receives Becotatug vedotin plus SBRT and systemic therapy.	Drug: Becotatug Vedotin; Becotatug vedotin was administered intravenously at a dose of 2.0 mg/kg every 3 weeks (Q3W).; Radiation: SBRT; All oligometastatic lesions will be treated with SBRT with curative intent. Radiation doses are determined based on published clinical studies; Drug: Systemic Therapy/Standard of Care; Systemic therapy /Standard of Care will be determined at the investigator's discretion, in accordance with clinical guidelines and individual patient characteristics.
Active Comparator: SBRT and systemic therapy arm; For patients in the control group receives SBRT and systemic therapy.	Radiation: SBRT; All oligometastatic lesions will be treated with SBRT with curative intent. Radiation doses are determined based on published clinical studies; Drug: Systemic Therapy/Standard of Care; Systemic therapy /Standard of Care will be determined at the investigator's discretion, in accordance with clinical guidelines and individual patient characteristics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Defined as the time interval from randomization to death due to any cause.	1 year
Objective Response Rate (ORR)	Defined as the proportion of patients whose tumors shrink to complete response (CR) or partial response (PR) and remain for a certain period of time according to RECIST 1.1.	3 months after SBRT
Disease Control Rate (DCR)	Defined as the proportion of patients whose tumors shrink to complete response (CR), partial response (PR) or stable disease (SD) and remain for a certain period of time according to RECIST 1.1.	3 months after SBRT
Duration of Response (DoR)	Defined as the time from the first documented Complete Response (CR) or Partial Response (PR) to the first documented disease progression (PD) or death from any cause in patients with an objective response	1 year
Health related quality of Life	The quality of life was evaluated by referring to the European EORTC Quality of Life Questionnaire Core 30 (QLQ-C30, version 3.0) . The scores range from 0 to 100, with higher scores indicating a better quality of life outcome and lower scores indicating worse symptoms or functions.	Baseline, after every two cycles of systemic therapy, before SBRT, after SBRT, and at each follow-up.
Incidence of treatment related acute complications	The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria.	During systemic therapy and up to three months after SBRT
Incidence of treatment related late complications	The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria.	More than three months after SBRT

Collaborators and Investigators

• Sponsor: Ming-Yuan Chen
• Collaborators: Fifth Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Mingyuan Chen, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2026
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: March 15, 2026
• First Submitted That Met QC Criteria: March 15, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 28, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: SBRT; MMAE; EGFR-postive oligo-metastatic cancer; Becotatug vedotin
• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: ZDWY.FSZLK.008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data can be requested from the corresponding author beginning 1 year after publication of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No