Clinical trial NCT05187338: Triplex Checkpoint Inhibitors Therapy for Advanced Solid Tumors
Official title: Triplex CTLA4/PD1/PDL1 Checkpoint Inhibitors Combination Therapy for Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Liver Cancer
Colorectal Cancer
Pancreas Cancer
Ovary Cancer
Head and Neck Cancer
Breast Cancer
Gastric Cancer
Cervical Cancer
Esophageal Cancer
Sarcoma
Keywords: Solid tumor
CTLA4 antibody
PD1 antibody
PDL1 antibody
Interventional Radiology
Trans-artery infusion
Intra-tumor injection
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2022-01-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by infusion of CTLA4, PD1 and PDL1 antibodies combination through venous (IV), artery (IA) or intra-tumor (IT).

Detailed description: Malignant solid tumors including lung and liver cancers are the most common malignancy worldwide, and their mortality rates are very high. China has a huge population base with about 4,000,000 new cancer cases each year. More than 60% of the solid tumors in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Recently a lot of therapeutic strategies have been developed and applied to clinic including targeted therapy and immunotherapy, but the overall therapeutic efficiency is still low. It is very difficult to treat patients with recurrent/refractory/metastatic advanced solid cancers and more alternative therapies are urgently needed.

Antibodies against CTLA4, PD1 and PDL1 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab, PD1 antibody and PDL1 antibody, so called triplex checkpoint inhibitors combination therapy, for advanced solid tumors. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the triplex checkpoint inhibitors combination therapy for cancer patients. This phase I-II clinical trial is designed to assess the safety and survival benefit of ipilimumab, pembrolizumab and durvalumab combination on patients with advanced solid cancers, including PFS, ORR, DCR, and median survival time.

Eligibility criteria: Inclusion Criteria:

1. Cytohistological confirmation is required for diagnosis of cancer.
2. Signed informed consent before recruiting.
3. Age above 18 years with estimated survival over 3 months.
4. Child-Pugh class A or B/Child score \> 7; ECOG score \< 2
5. Tolerable coagulation function or reversible coagulation disorders
6. Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR \< 2.3 or PT \< 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin \> 28 g/L；Total bilirubin \< 51 μmol/L
7. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
8. Birth control.
9. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

1. Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
2. Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
3. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
4. Patients accompanied with other tumors or past medical history of malignancy;
5. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
6. Patients have poor compliance.

   Any contraindications for hepatic arterial infusion procedure:

   A.Impaired clotting test (platelet count \< 60000/mm3, prothrombin activity \< 50%).

   B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (\> 160/100 mm/Hg).
7. Allergic to contrast agent;
8. Any agents which could affect the absorption or pharmacokinetics of the study drugs
9. Other conditions that investigator decides not suitable for the trial.

Primary outcomes:
measure: Safety of 3 drugs combination treatment
timeFrame: 5 years
measure: Progression-free survival
timeFrame: 5 years
measure: Disease control rate
timeFrame: 5 years
measure: Duration of remission (DOR)
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Zhenfeng Zhang, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: