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.
• 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.
⁃ ECOG performance status of 0-1.
⁃ Life expectancy \>= 6 months.