This phase I/II trial aims to evaluate safety and efficacy of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody in subjects with unresectable/ metastatic solid tumors. Patients will receive the combined regimen in 3-week treatment cycles. During the Phase 1 dose escalation portion of the trial, three oral doses of SHR2150 will be combined with intravenous administration of chemotherapy and PD-1 or CD47 antibody. In the Phase 2 dose expansion portion, patients will be treated with the Recommended Phase 2 Dose (RP2D) of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody.
Identification of T cell inhibitory signals, including PD-1/L1, has prompted the development of a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. However, elimination of cancer by T cells is only one step in the cancer-immunity cycle, which enable providing several therapeutic targets and tailoring of combinations of immune therapies. SHR2150 is a small molecule agonist of toll-like receptors (TLRs) 7 designed to activate antigen-presenting cells and functions as mucosal immunoadjuvants in pre-clinical studies. This study is a first-in-man, Phase I/II, dose escalation/expansion study of a combined regimen of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody in subjects with unresectable/ metastatic solid tumors. This study is designed to assess the safety, tolerability, RP2D and clinical efficacy of this regimen.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Patients will receive escalating doses of SHR-2150 (starting dose 2 mg) in 3-week treatment cycles.
The previously resistant first-line cytotoxic regimens, anti-PD-1 antibody and/or anti-CD47 antibody will be administered intravenously Q3W.
Patients will receive SHR-2150 at RP2D in 3-week treatment cycles.
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGSafety of the combined regimen of SHR2150, chemotherapy, PD-1 or CD47 antibody
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit.
Time frame: 60 days after last dose
Identify a RP2D of SHR2150 when given in combined regimen
The Recommended Phase 2 Dose (RP2D) of SHR2150 in the combined regimen will be identified at Phase 1 dose escalation period, and will be used in the phase 2 dose expansion period.
Time frame: 30 days
Object response rate (ORR)
ORR is defined as the proportion of subjects who achieved a partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: 24 month
Disease control rate (DCR)
DCR is defined as the proportion of subjects who achieved a stable disease (SD), partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: 24 months
Progression-free survival (PFS)
PFS was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per the RECIST V1.1.
Time frame: 24 months
Duration of Response (DOR)
DOR is defined as the time from the date of first documented response that is subsequently confirmed until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint. If the disease does not progress after a response, their duration of response will use the PFS censoring time.
Time frame: 24 months
Overall survival (OS)
OS was measured from the study entry to the date of death.
Time frame: 24 months
Time to Response (TTR)
TTR is defined as the period from the date of first dose to the date of the first evaluated response of CR or PR. If the response is not confirmed, it will not be included.
Time frame: 6 months
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