SBRT combined with becotatug vedotin for EGFR‑positive oligometastatic cancer

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

This trial will try combining focused radiation (SBRT) with the antibody‑drug conjugate becotatug vedotin plus standard systemic therapy for adults with EGFR‑positive oligometastatic solid tumors to see if it improves disease control and survival.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, immunotherapy, Radiation, vicetuximab
• Locations: 2 sites (Zhuhai, Guangdong and 1 other locations)
• Trial ID: NCT07481799 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial pairs stereotactic body radiotherapy (SBRT) to up to five metastatic lesions with investigator‑selected systemic therapy plus the antibody‑drug conjugate becotatug vedotin (MRG003), which delivers the radiosensitizing payload MMAE. Adults aged 18–75 with histologically or cytologically confirmed recurrent or metastatic EGFR‑positive solid tumors, a controlled primary site, and ≤5 oligometastatic lesions are eligible and must provide tumor tissue for EGFR testing. Participants receive local consolidative SBRT along with systemic therapy chosen by the investigator and scheduled doses of becotatug vedotin while safety, tumor response, and survival are tracked. The study seeks to determine whether adding this targeted ADC to SBRT and standard systemic care can improve outcomes for this selected patient group.

Who should consider this trial

Good fit: Adults 18–75 with histologically or cytologically confirmed EGFR‑positive recurrent or metastatic solid tumors, a controlled primary tumor, ≤5 metastatic lesions, and the ability to provide tumor tissue for EGFR testing are the intended candidates.

Not a fit: Patients with more than five metastatic lesions, uncontrolled primary tumors, non‑EGFR tumors, poor fitness for SBRT or systemic therapy, or inability to provide required tissue samples are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve local tumor control and prolong survival for a subset of patients with EGFR‑positive oligometastatic disease.

How similar studies have performed: Preclinical studies show MMAE can enhance radiosensitivity and early clinical work with EGFR‑targeting agents and ADCs has been promising, but large confirmatory trials combining SBRT with becotatug vedotin in this exact setting are not yet established.

Eligibility criteria

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.

Where this trial is running

Zhuhai, Guangdong and 1 other locations

• The Fifth Affiliated Hospital,Sun Yat-sen University — Zhuhai, Guangdong, China (NOT_YET_RECRUITING)
• The Fifth Affiliated Hospital,Sun Yat-sen University — Zhuhai, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Mingyuan Chen — Sun Yat-sen University
• Study coordinator: Mingyuan Chen

Conditions: Oligo-metastatic Cancer, EGFR-postive oligo-metastatic cancer, SBRT, MMAE, Becotatug vedotin