Spatially targeted radiation followed by shorter or standard radiotherapy with iparomlimab and tuvonralimab for relapsed bulky solid tumors

A Study of Spatially Fractionated Radiation Therapy Followed by Sequential Hypofractionated or Conventional Fractionated RT Combined With Iparomlimab and Tuvonralimab for Relapsed and Refractory Bulky Solid Tumors

This study will test whether targeted 'spatially fractionated' radiation followed by shorter or standard radiotherapy combined with two immunotherapy drugs (iparomlimab and tuvonralimab) is safe and helpful for adults with relapsed or refractory bulky solid tumors.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital of Nanchang University (other)
• Drugs / interventions: prednisone, Iparomlimab, Tuvonralimab, Immunotherapy, Radiation
• Locations: 1 site (Nanchang, Jiangxi)
• Trial ID: NCT06936748 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-arm, open-label phase 2 study enrolling about 30 adults with relapsed or refractory bulky solid tumors (≥6 cm). Participants receive spatially fractionated radiation therapy (SFRT) to large tumors, followed by sequential hypofractionated or conventional fractionated radiotherapy together with infusions of iparomlimab and tuvonralimab. The primary endpoint is safety (incidence and severity of treatment-related adverse events); secondary endpoints include objective response rate, disease control rate, duration of response, progression-free survival, and overall survival. Exploratory biomarker analyses will examine PD-L1 and plasma cytokines (e.g., IL-2, IL-10) to look for correlations with outcomes.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed relapsed or refractory solid tumors that include at least one measurable lesion ≥6 cm, ECOG 0–2, adequate organ function, expected survival ≥3 months, and a washout of prior anti-tumor therapy >4 weeks are the intended participants.

Not a fit: Patients with small tumors (<6 cm), poor performance status (ECOG >2), inadequate organ function, active uncontrolled illness, or who cannot tolerate radiation or immunotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could offer a new safe treatment option that helps shrink large, previously treated tumors and improve disease control for patients with bulky relapsed cancers.

How similar studies have performed: Previous small studies combining spatially fractionated or high‑dose focal radiation with immunotherapy have shown promising signals, but using iparomlimab and tuvonralimab together in this exact regimen is novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

1. Age 18-75 years, male or female.
2. Histologically confirmed malignant tumor in the past.
3. Disease recurrence after treatment, including local regional relapsed and distant metastasis.
4. At least one measurable lesion with a maximum diameter greater than 6 cm, unsuitable for conventional surgery, ablation, or other treatments.
5. ECOG: 0-2 points.
6. Expected survival ≥3 months.
7. Washout period of previous anti-tumor treatment \>4 weeks.
8. The patient agrees and signs the informed consent form.
9. The function of vital organs meets the following requirements (no use of any blood components, cell growth factors, leukocyte boosters, platelet boosters, or anemia correction drugs within 14 days prior to the first use of the study drug):

   1. Absolute neutrophil count (ANC) ≥1.5×10\^9/L;
   2. Platelets ≥90×10\^9/L;
   3. Hemoglobin ≥8g/dL;
   4. Serum albumin ≥2.8g/dL;
   5. Total bilirubin ≤1.5×ULN, ALT, AST, and/or AKP ≤2.5×ULN; if liver metastasis is present, ALT and/or AST ≤5×ULN; if liver or bone metastasis is present, AKP ≤5×ULN;
   6. Serum creatinine ≤1.5×ULN or creatinine clearance rate greater than 60 mL/min;
   7. Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5×ULN (patients on stable doses of anticoagulation therapy such as low molecular weight heparin or warfarin with INR within the expected therapeutic range can be screened).
10. Negative pregnancy test for female subjects (for female patients of childbearing potential);
11. The subject voluntarily joins the study, signs the informed consent form, has good compliance, and cooperates with follow-up;
12. The investigator believes that the patient may benefit.

Exclusion Criteria:

1. History of severe immediate hypersensitivity reaction to any of the drugs used in this study.
2. Any of the following conditions within 6 months prior to screening: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. Patients known to have coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \<50% must be on an optimized stable medical regimen as determined by the treating physician; consultation with a cardiologist may be appropriate if necessary.
3. History of receiving anti-tumor vaccines or live vaccines within 4 weeks prior to the first dose of the investigational drug.
4. Active autoimmune diseases or history of autoimmune diseases that may recur. However, patients with the following conditions are not excluded and can proceed to further screening:

   1. Controlled Type 1 diabetes
   2. Hypothyroidism (if it can be controlled with hormone replacement therapy alone)
   3. Skin conditions that do not require systemic therapy (e.g., vitiligo, psoriasis, alopecia)
   4. Any other condition not expected to recur without external triggering factors
5. Lack of civil capacity or limited civil capacity.
6. Physical or mental conditions that impair the patient's ability to fully or adequately understand the potential complications of this study, as judged by the investigator.
7. Patients with an expected survival of less than 3 months.
8. Patients with significantly diminished cardiac, hepatic, pulmonary, renal, and bone marrow function.
9. Drug abuse or alcohol addiction.
10. Tumor lesions invading major blood vessels such as the internal carotid artery and vein and their major branches, posing a high risk of bleeding.
11. Subjects requiring systemic treatment with corticosteroids (more than 10mg/day prednisone equivalent dose) or other immunosuppressive agents within 2 weeks prior to the first use of the investigational drug, except for the use of corticosteroids for local esophageal inflammation and prevention of allergies and nausea/vomiting. Special cases need to be discussed with the sponsor. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal corticosteroid replacements at doses \>10mg/day prednisone equivalent are allowed.
12. History of immunodeficiency, including HIV-positive status, or other acquired or congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation.
13. Pregnant or breastfeeding female patients, male or female patients of childbearing potential who are unwilling or unable to use contraception for at least 1 year after the end of the treatment protocol throughout the study period.
14. The investigator deems the patient unsuitable for inclusion.

Where this trial is running

Nanchang, Jiangxi

• The Second Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (RECRUITING)

Study contacts

• Principal investigator: Anwen Liu, Ph.D. — Second Affiliated Hospital of Nanchang University
• Study coordinator: Anwen Liu, Ph.D.

Conditions: Cancer, Bulky Solid Tumors, Spatially Fractionated Radiation Therapy, Immunotherapy, Iparomlimab and Tuvonralimab