SFRT+Sequential Hypofractionated/Conventional Fractionated RT+Iparomlimab and Tuvonralimab for Relapsed/Refractory Solid Tumors

NCT06936748 | Recruiting Phase 2 DMC

• 1 other identifier: IIT-I-2025-014
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Study Objectives Primary Objective:To evaluate the safety of SFRT followed by hypofractionated/conventional fractionated radiotherapy combined with Iparomlimab and Tuvonralimab Injection in relapsed/refractory bulky solid tumors. Secondary Objectives:To assess efficacy (objective response rate, disease control rate, progression-free survival, etc.) and identify predictive biomarkers.To explore correlations between immunologic biomarkers (e.g., PD-L1 expression, plasma IL-2/IL-10) and treatment outcomes. Study Endpoints Primary: Safety (incidence/severity of treatment-related adverse events). Secondary: ORR, DCR, DoR, mPFS, mOS Exploratory: Biomarker analysis (PD-L1, IL-2, IL-10).

Conditions

Cancer

Keywords

Bulky Solid Tumors; Spatially Fractionated Radiation Therapy; Immunotherapy; Iparomlimab and Tuvonralimab

Outcome Measures

Primary Outcomes (1)

• Safety (treatment-related toxicity and adverse reactions)

  Adverse events (treatment toxicity) will be evaluated using NCI-CTCAE version 5.0.

  The safety endpoints will be assessed by a review of adverse events and serious adverse events according to CTCAE up to 1 year after end of treatment

Secondary Outcomes (6)

• Complete Response (CR) rate

  One imageological examination will be performed during the baseline period, followed by another imageological examination after the completion of radiotherapy. During immunotherapy, imaging assessments will be conducted every 3 treatment cycles.

• Duration of Response (DoR)

  One imageological examination will be performed during the baseline period, followed by another imageological examination after the completion of radiotherapy. During immunotherapy, imaging assessments will be conducted every 3 treatment cycles.

• Objective Response Rate (ORR)

  One imageological examination will be performed during the baseline period, followed by another imageological examination after the completion of radiotherapy. During immunotherapy, imaging assessments will be conducted every 3 treatment cycles.

• Median Progression-Free Survival (mPFS)

  One imageological examination will be performed during the baseline period, followed by another imageological examination after the completion of radiotherapy. During immunotherapy, imaging assessments will be conducted every 3 treatment cycles.

• Disease Control Rate (DCR)

  One imageological examination will be performed during the baseline period, followed by another imageological examination after the completion of radiotherapy. During immunotherapy, imaging assessments will be conducted every 3 treatment cycles.

Study Arms (1)

Radiotherapy Combined with Immunotherapy

EXPERIMENTAL

This is a single-arm study. Treatment Protocol Radiotherapy Phase: SFRT: 10-20 Gy/1 fraction to the tumor. Sequential Radiotherapy:Hypofractionated Radiotherapy: 20-70 Gy total (3-12.5 Gy/fraction) or Conventional Fractionated Radiotherapy: 50-70 Gy total (1.8-2.5 Gy/fraction).Dose determined by investigator. Immunotherapy Phase: Iparomlimab and Tuvonralimab: Dose: 5 mg/kg IV every 3 weeks (Day 1). Infusion: Diluted in 100 mL saline/5% glucose, administered over 20-60 minutes. Duration: Until disease progression, intolerable toxicity, new antitumor therapy, or up to 1 year. Progression Management: Continuation post-progression permitted after investigator-patient discussion; permanent discontinuation upon re-progression.

Combination Product: Spatially Fractionated Radiation Therapy Followed by Sequential Hypofractionated or Conventional Fractionated Radiotherapy Combined with Iparomlimab and Tuvonralimab

Interventions

Spatially Fractionated Radiation Therapy Followed by Sequential Hypofractionated or Conventional Fractionated Radiotherapy Combined with Iparomlimab and Tuvonralimab COMBINATION_PRODUCT

Radiotherapy Phase: Spatially fractionated radiotherapy (SFRT, 10-20 Gy/1F) to the tumor, followed by hypofractionated/conventional fractionated radiotherapy (dose investigator-determined). Immunotherapy Phase: Iparomlimab and Tuvonralimab (5 mg/kg) initiated within 1 week post-radiotherapy, infused IV over 20-60 minutes (Day 1, every 3 weeks) in 100 mL saline/5% glucose. Treatment continues until disease progression, intolerable toxicity, new antitumor therapy, consent withdrawal, or investigator decision, with a maximum duration of 1 year. Progression may allow continued therapy after patient-investigator discussion; re-progression mandates permanent discontinuation.

Radiotherapy Combined with Immunotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years, male or female.
• Histologically confirmed malignant tumor in the past.
• Disease recurrence after treatment, including local regional relapsed and distant metastasis.
• At least one measurable lesion with a maximum diameter greater than 6 cm, unsuitable for conventional surgery, ablation, or other treatments.
• ECOG: 0-2 points.
• Expected survival ≥3 months.
• Washout period of previous anti-tumor treatment \>4 weeks.
• The patient agrees and signs the informed consent form.
• 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):
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L;
• Platelets ≥90×10\^9/L;
• Hemoglobin ≥8g/dL;
• Serum albumin ≥2.8g/dL;
• 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;
• Serum creatinine ≤1.5×ULN or creatinine clearance rate greater than 60 mL/min;

You may not qualify if:

• History of severe immediate hypersensitivity reaction to any of the drugs used in this study.
• 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.
• History of receiving anti-tumor vaccines or live vaccines within 4 weeks prior to the first dose of the investigational drug.
• 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:
• Controlled Type 1 diabetes
• Hypothyroidism (if it can be controlled with hormone replacement therapy alone)
• Skin conditions that do not require systemic therapy (e.g., vitiligo, psoriasis, alopecia)
• Any other condition not expected to recur without external triggering factors
• Lack of civil capacity or limited civil capacity.
• 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.
• Patients with an expected survival of less than 3 months.
• Patients with significantly diminished cardiac, hepatic, pulmonary, renal, and bone marrow function.
• Drug abuse or alcohol addiction.
• Tumor lesions invading major blood vessels such as the internal carotid artery and vein and their major branches, posing a high risk of bleeding.
• 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.

Sponsors & Collaborators

• Second Affiliated Hospital of Nanchang University: lead
• Qilu Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

MeSH Terms

Conditions

Neoplasms

Study Officials

• Anwen Liu, Ph.D.

  Second Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anwen Liu, Ph.D.

CONTACT

+8613767120022; awliu666@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: April 20, 2025
• Study Start: June 20, 2025
• Primary Completion (Estimated): June 19, 2028
• Study Completion (Estimated): June 19, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)