The primary objective of Phase I of this trial is to evaluate the safety, tolerability, maximum tolerated dose (MTD)/maximum administered dose (MAD) of RC148 in patients with locally advanced unresectable or metastatic solid tumors to determine the recommended Phase II dose (RP2D), and the secondary objective is to evaluate the PK and PD characteristics, immunogenicity and preliminary clinical efficacy of RC148. Phase II will primarily evaluate the efficacy of the RC148 combination regimen, and secondarily will assess safety and tolerability, PK characteristics, and immunogenicity. During the trial, investigators will also evaluate the potential correlation of biomarkers with efficacy.
Be able to participate in the study voluntarily and willing to provide written informed consent.
male or female ≥18 years (phase Ⅰ), 18 to 75 years old (Including 18 and 75 years, phase Ⅱ).
Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Projected life expectancy of at least 12 weeks.
Pregnant or lactating.
Cohort 1 in Phase II, patients with histologically or cytologically confirmed non-small cell lung cancer, other than squamous lung cancer and lung adenocarcinoma, (including subjects with squamous or adenocarcinoma in combination with other pathologic types of non-small cell lung cancer;) prior treatment with docetaxel, or an antitumor agent that targets VEGF/VEGFR; and treatment with at least 2 cycles of an immune checkpoint inhibitor, with a best response of PD, or best response of CR/PR/SD with disease progression within 6 months of first dose.
Cohorts 4-7 in Phase II, patients with ocular corneal conditions at screening such as congenital corneal dystrophy, meibomian gland dysfunction (MGD), viral keratitis (dendritic, map-like, corneal stromal keratitis), uveitis, corneal endothelial decompensation, glaucoma, iridocorneal endothelial syndrome (ICE).
Subjects with active hepatitis B or C; human immunodeficiency virus (HIV)-positive subjects.
Parallel
RC148 Monotherapy
DrugRC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle
RC148+docetaxel Combination Therapy
DrugRC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle； Docetaxel will be administered as an IV infusion on Day 1 of each 3-week cycle.
RC148+RC48 Combination Therapy
DrugRC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 2-week cycle； RC48 will be administered as an IV infusion on Day 1 of each 2-week cycle.
RC148+RC88 Combination Therapy
DrugRC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle； RC88 will be administered as an IV infusion on Day 1 of each 3-week cycle.
RC148/Bevacizumab+RC88 Combination Therapy
DrugRC148 injection will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle; RC88 will be administered as an IV infusion on Day 1 of each 3-week cycle; Bevacizumab will be administered as an IV infusion on Day 1 of each 3-week cycle
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Treatment groupsSee each treatment group below.
Phase I：Maximum tolerated dose (MTD)/Maximum administered dose (MAD)
MTD/MAD based on number of Dose limiting toxicity (DLT)
Phase I：DLT
In the DLT evaluation window (observation period 1-28 days after the first administration), according to the NCI-CTCAE v5.0 grading standard, the investigator or the sponsor believes that toxic reaction which are reasonably related to RC148 treatment
Phase I：The incidence and severity of adverse events (AE)
Adverse events were assessed by investigator(s) according to NCI-CTCAE v5.0
Phase I：Recommended Phase 2 dose (RP2D)
The RP2D may be selected as 1 dose level lower than the MTD and will be determined in discussion with the safety monitoring committee based on all available data
Phase I：Overall Response Rate (ORR)
Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)
Phase I：DCR
Disease Control Rate was defined as the percentage of participants with a CR or PR or stable disease (SD)
Phase I：DOR
Duration of response is the length of time that a tumor continues to respond to treatment without the cancer growing or spreading
Phase I：PFS
Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
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