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.
Be able to participate in the study voluntarily and willing to provide written informed consent.
male or female 18 ≤ age ≤ 75 years old.
Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
The expected survival ≥12 weeks.
Pregnant women, breastfeeding women or women with a positive blood pregnancy test result during the screening period (non-fertile women do not need to undergo a pregnancy test, such as women with a previous hysterectomy and/or bilateral oophorectomy or amenorrhea ≥12 months).
Subjects with active hepatitis B (HBsAg positivity and HBV DNA titre higher than the normal upper limit), active hepatitis C (HCVAb positivity and HCV RNA titre higher than the normal upper limit), and positive human immunodeficiency virus antibody (HIV-Ab) results during the screening period.
Subjects with a history of other acquired or congenital immunodeficiency diseases, or who have undergone organ or bone marrow transplantation.
Subjects who have previously received monoclonal antibody, double antibody targeting drugs, ADC, CAR-T and other therapeutic drugs targeting Claudin 18.2 or other ADCs with MMAE payload; or have participated in clinical trials and received investigational drugs within 4 weeks before the first dose.
Sequential
RC118
DrugDose A or dose B, Q2W
Toripalimab
DrugFixed dose, Q3W
RC148
DrugFixed dose, Q3W Other Names: RC148 injection
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.
Phase1/2: Adverse events (AEs)
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.
Phase1: Maximum tolerated dose(MTD)
Maximum tolerated dose(MTD)
Phase1: Recommended Phase 2 Dose (RP2D)
Recommended Phase 2 Dose (RP2D)
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)
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).
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.
Overall survival (OS)
The time from the date of the first dose of study treatment to the date of death.
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