The goal of this clinical trial is to assess the safety and tolerability of AT1019 when used in combination with SBRT and PD-1 inhibitor, and determine the maximum tolerated dose (MTD) of AT1019 in the combination therapy of SBRT and PD-1 inhibitor in patients with advanced solid tumors. The main questions it aims to answer are:
Is the combination of AT1019, SBRT and PD-1 inhibitor safe and well-tolerated in patients with advanced solid tumors? What is the maximum tolerated dose (MTD) of AT1019 when combined with SBRT and PD-1 targeted immunotherapy?
Participants will:
* First receive PD-1 inhibitor treatment as scheduled. * Undergo SBRT, which will be given in 3 to 5 fractions, with each fraction ranging from 6Gy to 18Gy, and the treatment will be administered once a week. * Receive intratumoral injection of AT1019 within 1 to 2 days after each SBRT session. * Undergo imaging examinations every 6 weeks (with a tolerance of ±1 week) to evaluate the treatment effect.
Male or female patients aged ≥ 18 years.
Signed the informed consent form and have the psychological capacity to understand it.
Patients with advanced solid malignant tumors (such as non-small cell lung cancer, renal cell carcinoma, head and neck cancer, cervical cancer, and urothelial carcinoma) who are receiving immunotherapy and planned to undergo SBRT. Patients are eligible if they achieved at least stable disease during previous immunotherapy.
Patients' disease must be evaluated according to RECIST v.1.1.
Previous therapeutic radiotherapy to the same lesion.
Failure to recover to grade 1 or lower from clinically significant adverse events related to prior anticancer therapy, as judged by the investigator.
Previous grade 4 toxicity attributed to immunotherapy.
Known untreated brain metastases or treated but unstabilized brain metastases (central nervous system lesions shown on scan to be non-progressive and not requiring corticosteroid use) ≥ 4 weeks prior to enrollment.
Single group
AT1019
Drug1. First receive PD-1 inhibitor treatment. 2. Undergo SBRT, which will be given in 3 to 5 fractions, with each fraction ranging from 6Gy to 18Gy, and the treatment will be administered once a week. 3. Receive intratumoral injection of AT1019 within 1 to 2 days after each SBRT session.
Dose-limiting toxicity (DLT)
Determine the DLT of AT1019 in the combination therapy of SBRT and PD-1 inhibitor.
Maximum tolerated dose (MTD)
Determine the MTD of AT1019 in the combination therapy of SBRT and PD-1 inhibitor.
Adverse event (AE)
Rates and severity of AEs assessed by CTCAE v5.0 criterion.
Abscopal effect rate
The proportion of patients with an abscopal response assessed by RECIST v1.1 criterion.
Objective response rate (ORR)
To evaluate ORR of AT1019 in combination with SBRT and PD-1 inhibitor based on RECIST v1.1 criterion.
Disease control rate (DCR)
To evaluate DCR of AT1019 in combination with SBRT and PD-1 inhibitor based on RECIST v1.1 criterion.
Progress-free survival (PFS)
To evaluate PFS of AT1019 in combination with SBRT and PD-1 inhibitor. PFS was defined from date of recruit to date of first documentation of progression or death due to any cause.
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