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A Multiple Tumor Species, Open and Multi-center Clinical Study of Alpaloritovorelli Antibodies (QL-1706) Combined with Pulsed Low Dose Rate External Irradiation (PLDR) for Disease Progression After Previous Anti-tumor Therapy | Clinical Trials | Clareo Health

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A Multiple Tumor Species, Open and Multi-center Clinical Study of Alpaloritovorelli Antibodies (QL-1706) Combined with Pulsed Low Dose Rate External Irradiation (PLDR) for Disease Progression After Previous Anti-tumor Therapy

NCT06760676•Anhui Provincial Hospital

View on ClinicalTrials.gov

Summary

Detailed Description

For the recurrent and metastatic tumors after first-line treatment (such as lung cancer, esophageal cancer and cervical cancer), the risk of conventional fractionated secondary radiotherapy is high because the tumor is close to the hollow organs (such as heart, lung and small intestine). According to previous studies, combined chemotherapy regimens are often used, but the disease control rate (DCR) is limited, and drug resistance and poor tolerance of patients are prone to occur. The immune checkpoint inhibitors (ICB) has been considered as a new strategy for maintenance treatment of patients with recurrent and metastatic tumors, but only some patients can respond for a long time. Therefore, how to improve the clinical response rate of ICB has become an urgent problem to be solved. Pulsed low dose rate radiotherapy (PLDR), a new radiotherapy technology emerging in recent years, is expected to become a new way to solve the above difficulties. PLDR technology was first proposed by Tom é et al in 2007, and was first applied to the re-radiotherapy of recurrent tumors by Richards and Charlie Ma et al. The primary principle is the low-dose high radiosensitivity (HRS) of radiobiology, that is, a certain low-dose level of radiotherapy can increase the radiosensitivity of tumor cells and reduce the toxicity of normal tissues at the same time. Alpaloritovorelli antibodies (QL-1706) is a new type of combination antibody independently developed by Qilu Pharmaceutical Co., Ltd. It is composed of IgG4 antibody targeting PD-1 (ipalorimab), and IgG1 antibody targeting CTLA-4 (tuvonralimab) in a fixed proportion. It has the synergistic mechanism of blocking PD-1 and CTLA-4 at the same time. The combination of these two antibodies forms a powerful synergistic effect and forms positive feedback in the tumor immune cycle. The combination antibody can maintain normal PD-1 antibody exposure in vivo and reduce the half-life of CTLA-4 antibody with lower toxicity and better tolerance. At present, sufficient preclinical studies of alpaloritovorelli antibodies have been completed, and a number of clinical studies are under way. The mechanism of action, safe dose range, mode of administration, toxicity characteristics and pharmacological characteristics are clear. Clinical research data show that the combination antibody of alpaloritovorelli is safe, controllable and tolerable in patients with solid tumors, and has shown encouraging efficacy in cervical cancer and other multiple tumors. Based on the results of DUBHE-C-206 trial, the combination antibody was approved by the China food and Drug Administration on September 30 of 2024, and the phase I safety test has been completed in the United States. Pulsed low dose rate radiotherapy (PLDR) is a safe and feasible option for recurrent tumors with high risk of re-radiotherapy. It also has therapeutic advantages for refractory and massive tumors. The advantages of combined vascular targeting and chemotherapy have been initially demonstrated. As a new anti-tumor therapy, immunotherapy has shown clinical benefits in many types of cancer, but the overall effective rate is still limited, which may be due to the immune "desertification" of the tumor microenvironment. PLDR irradiation is expected to reverse the tumor inhibitory microenvironment by inducing the release of tumor associated antigen and increasing the killing function of T cells, activate tumor immunity and improve the response rate of immunotherapy. Based on this, this study plans to take the lead in carrying out this prospective clinical study through the combination of PLDR external irradiation and ICB treatment (QL-1706).

Eligibility

Age

18 - 75 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. The subjects voluntarily joined this study, signed informed consent, had good compliance, and were willing to cooperate with follow-up;
•2. Male or female, age range of 18-75 years old (including 18 and 75 years old), gender not limited;
•3. Confirmed by pathology as esophageal cancer, non-small cell lung cancer, or cervical cancer;
•4. Expected survival period\>3 months;
•5. Patients who have progressed with first-line treatment in the past, (patients with local recurrence or distant metastasis of the tumor during (new) adjuvant therapy or ≤ 3 months after treatment are considered as first-line treatment)
•6. ECOG score 0-2 points;
•7. According to RECIST 1.1 criteria, there must be at least one measurable extracranial lesion;
•8. The laboratory test results within one week before enrollment meet the following conditions: 1) Blood routine: HGB≥90g/L； WBC≥4.0×109/L； NEUT≥2.0×109/L； PLT ≥100×109/L； 2) Blood biochemistry: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN (ALT and AST ≤ 5 × ULN in patients with liver metastases); BUN and Cr ≤ 1.5 × ULN and creatinine clearance rate ≥ 50 mL/min; 3) The results of cardiac ultrasound examination within the first two weeks of enrollment are consistent: left ventricular ejection fraction (LVEF)\>50%;
•9. Normal coagulation function, no active bleeding or thrombotic diseases;
•10. Patients without contraindications for radiotherapy;
+2 more criteria

Exclusion Criteria

•1. Patients with malignant tumors other than cervical cancer, esophageal cancer, and lung cancer;
•2. In the first 5 years of randomization, patients with other active malignant tumors, except for locally curable tumors that have been cured, such as skin squamous cell carcinoma, skin basal cell carcinoma, superficial bladder cancer, and breast cancer in situ;
•3. Patients who have participated in clinical trials of other drugs within the 4 weeks prior to enrollment, received radiation therapy targeting the target area within the 4 weeks prior to enrollment in this study, and received attenuated live vaccines within the 4 weeks prior to their first dose or planned to receive them during the study period; Within 4 weeks before the first administration, he received systematic treatment with traditional Chinese patent medicines and simple preparations with anti-tumor indications or Chinese herbal medicine with anti-tumor effect and drugs with immune regulation effect (such as thymosin, interferon, interleukin, etc.);
•4. Within 6 months, there have been incidents of arterial/venous thrombosis, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
•5. Simultaneously receiving any other anti-tumor treatment;
•6. Individuals with a known history of allergies to the components of this medication regimen, a history of telangiectatic ataxia or other radiation hypersensitivity reactions;
•7. Subjects with active infectious diseases;
•8. Subjects with any severe and/or uncontrolled illnesses;
•9. Pregnant and lactating female patients, female patients with fertility and positive baseline pregnancy test results;
•10. According to the investigator's judgment, there are concomitant diseases (including but not limited to severe hypertension, severe pulmonary dysfunction/disease, and severe diabetes beyond the control of drugs) that seriously endanger the patient's safety or affect the patient's completion of the study;
+13 more criteria

Key Dates

Start Date

December 1, 2025

Primary Completion Date

May 31, 2027

Completion Date

July 31, 2027

Last Updated

January 7, 2025

Enrollment

ESTIMATED participants

Conditions

Esophageal CancerNon Small Cell Lung CancerCervical Cancer

Interventions

Pulsed low dose rate radiotherapy (PLDR)

RADIATION

Alpaloritovorelli antibodies

DRUG

Contacts

Pei jie Zhou, M.D.

CONTACT

+8618356148326 zhpejie@ustc.edu.cn

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 7, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Multiple Tumor Species, Open and Multi-center Clinical Study of Alpaloritovorelli Antibodies (QL-1706) Combined with Pulsed Low Dose Rate External Irradiation (PLDR) for Disease Progression After Previous Anti-tumor Therapy

Inclusion Criteria

Exclusion Criteria

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