This is an open, multi-center, dose escalation and expansion phase I/II study. The Phase I study will explore the tolerability and safety of RC118 in combination with Toripalimab for the treatment of patients with Claudin 18.2-positive, locally advanced unresectable or metastatic malignant solid tumors, and to establish the maximum tolerated dose (MTD) and the recommended dose in phase II clinical trials (RP2D); The Phase II study will evaluate the efficacy and safety of RC118 in combination with Toripalimab or RC148 in patients with locally advanced or metastatic Gastric cancer/Gastro-esophageal junction cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Dose A or dose B, Q2W
Fixed dose, Q3W
Fixed dose, Q3W Other Names: RC148 injection
Fujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGThe First Affiliated Hospital of Xiamen University
Xiamen, Fujian, China
RECRUITINGGansu Wuwei Tumour Hospital
Wuwei, Gansu, China
RECRUITINGMeizhou People's Hospital
Meizhou, Guangdong, China
RECRUITINGHarbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
RECRUITINGNanyang Central Hospital
Nanyang, Henan, China
RECRUITINGXinyang Central Hospital
Xinyang, Henan, China
RECRUITINGThe First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
RECRUITINGThe Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, China
RECRUITINGXuzhou Central Hospital
Xuzhou, Jiangsu, China
RECRUITING...and 8 more locations
Phase1: Dose limiting toxicity (DLT)
Toxicity occurs within the DLT evaluation window (1-21 days after the first dose) that the investigator or sponsor believes to be reasonably associated with RC118 or Toripalimab according to NCI-CTCAE v5.0.
Time frame: The first 3 weeks (21 days) after the start of dosing at each dose level
Phase1/2: Adverse events (AEs)
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.
Time frame: [Time Frame: 15 months]
Phase1: Maximum tolerated dose(MTD)
Maximum tolerated dose(MTD)
Time frame: up to 12 months
Phase1: Recommended Phase 2 Dose (RP2D)
Recommended Phase 2 Dose (RP2D)
Time frame: up to 12 months
Phase 2: Objective response rate (ORR)
The proportion of patients whose BOR is a confirmed CR or PR. Tumor response will be evaluated using RECIST v.1.1.
Time frame: 15 months
Disease Control Rate (DCR)
The percentage of patients who have achieved an objective response of confirmed CR ,PR or SD as assessed by the investigator per RECIST v1.1)
Time frame: 15 months
Progression-free survival (PFS)
The time from first dose to disease progression(as assessed by investigators according to RECIST v1.1 criteria) (as measured by the first event).
Time frame: 15 months
Duration of Remission (DOR)
The time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death.
Time frame: 15 months
Overall survival (OS)
The time from the date of the first dose of study treatment to the date of death.
Time frame: 15 months
Phase 1: Objective response rate (ORR)
The proportion of patients whose BOR is a confirmed CR or PR. Tumor response will be evaluated using RECIST v.1.1.
Time frame: 15 months
Peak and valley concentrations of RC118, total antibody, and free MMAE
Peak and valley concentrations of C118 binding antibody, total antibody, and free MMAE were observed.
Time frame: 15 months
RC118 immunogenicity: The incidence, time of onset, duration of patients with anti-drug-antibody (ADA)
RC118 immunogenicity: The incidence, time of onset, duration of patients with anti-drug-antibody (ADA)
Time frame: 15 months
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