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

Plain English Summary

Efficacy and Safety of SBRT Combined With Becotatug Vedotin (MRG003) in EGFR-Positive Metastatic Tumor Patients With Oligometastases is a Phase 3 clinical trial sponsored by Ming-Yuan Chen studying Oligo-metastatic Cancer. Tests the combination of SBRT and Becotatug Vedotin to improve outcomes in EGFR-positive metastatic tumors with oligometastases. For patients with EGFR-positive metastatic tumors and up to 5 metastatic sites, who have had their primary tumor treated. Participation involves SBRT for metastases and Becotatug Vedotin infusions every 3 weeks. Regular follow-ups and imaging are required. Alternative treatments include standard systemic therapies and other targeted therapies. The trial aims to enroll 200 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Ages 18-75, male or female, with EGFR-positive metastatic tumors and up to 5 metastatic sites. No history of severe hypersensitivity to monoclonal antibodies, and no prior treatment with EGFR ADCs or microtubule inhibitors. No active infections or recent treatments that could interfere with the study drugs. No severe comorbidities or ongoing immunosuppressive medications. This trial is studying Oligo-metastatic Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures, such as progression-free survival, will help patients understand if the treatment is effective in slowing tumor growth. The specific primary outcome measures are: Progression-free Survival (PFS) (1 year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a treatment gap by evaluating a novel combination therapy for EGFR-positive metastatic tumors, potentially offering better outcomes and survival. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Oligo-metastatic Cancer, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape indicate a high demand for effective treatments for EGFR-positive metastatic tumors, with a moderate approval probability. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about your eligibility and the potential benefits of participating in this trial. Understand that participation involves regular imaging and follow-ups, as well as receiving Becotatug Vedotin infusions every 3 weeks. This trial is currently recruiting participants. The trial is being conducted at 2 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 200 participants

Interventions

• 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.

Primary Outcomes

• Progression-free Survival (PFS) (1 year)

Secondary Outcomes

• 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.)

Full 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. Pres

Trial Locations

• The Fifth Affiliated Hospital,Sun Yat-sen University, Zhuhai, Guangdong, China
• The Fifth Affiliated Hospital,Sun Yat-sen University, Zhuhai, Guangdong, China

Frequently Asked Questions

Related Conditions

• EGFR-positive lung cancer, head and neck cancer, liver cancer, gastric cancer, pancreatic cancer, and other solid tumors.
• Oligometastatic cancer, metastatic disease, and advanced cancer treatments.

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