Oligo-metastatic Cancer
Conditions
Keywords
EGFR-postive oligo-metastatic cancer, SBRT, MMAE, Becotatug vedotin
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.
Interventions
Becotatug vedotin was administered intravenously at a dose of 2.0 mg/kg every 3 weeks (Q3W).
RADIATIONSBRT
All oligometastatic lesions will be treated with SBRT with curative intent. Radiation doses are determined based on published clinical studies
Systemic therapy /Standard of Care will be determined at the investigator's discretion, in accordance with clinical guidelines and individual patient characteristics.
Sponsors
Ming-Yuan Chen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 1 year | Defined as time from randomization to loco-regional or distant metastasis relapse or death from any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 1 year | Defined as the time interval from randomization to death due to any cause. |
| Objective Response Rate (ORR) | 3 months after SBRT | 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. |
| Disease Control Rate (DCR) | 3 months after SBRT | 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. |
| Duration of Response (DoR) | 1 year | 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 |
| Health related quality of Life | Baseline, after every two cycles of systemic therapy, before SBRT, after SBRT, and at each follow-up. | 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. |
| Incidence of treatment related acute complications | During systemic therapy and up to three months after SBRT | The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria. |
| Incidence of treatment related late complications | More than three months after SBRT | The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria. |
Countries
China
Contacts
CONTACTMingyuan Chen
CONTACTXiaoting Cai
PRINCIPAL_INVESTIGATORMingyuan Chen
Sun Yat-sen University
Outcome results
None listed