A Phase Ia/Ib open label，clinical study evaluating the safety, tolerability and preliminary efficacy of AK127 in combination with AK104 in patients with advanced malignant tumors
1.The subject must sign the written informed consent form(ICF) voluntarily. 2.Aged ≥ 18 to ≤ 75 years,male and female at the time of enrollment. 3.Eastern Cooperative Oncology Group(ECOG) performance status score of 0 or 1. 4.Life expectancy≥ 3 months. 5.Patients with histologically or cytologically confirmed advanced, recurrent, or metastatic malignancies were enrolled in the phase Ia dose escalation phase;Selected tumor species were enrolled in phase Ib dose extension.Patients with advanced metastatic malignancies who have failed first-line, or second-line, or third-line, or fourth-line standard therapies, or who not appropriate for standard treatment, cannot tolerate chemotherapy, or do not have effective standard therapies.
1. Previous treatment for:Use of small-molecule targeted antitumor drugs, monoclonal or double-clonal antibodies targeting PD-(L)1 or CTLA-4, other anti-tumor antibodies, other anti-tumor therapies (e.g., chemotherapy, radiotherapy, biological or hormonal therapy) within 4 weeks prior to initial administration of the study drug, previous use of immunomodulatory drugs within 2 weeks prior to initial administration of the study drug,Prior treatment with approved or investigational TIGIT antibodies, PVRIG antibodies, or CD96 antibodies.
Single group
AK127 Q3W IV infusion ,AK104 10mg/kg Q3W IV infusion
DrugAK127 is administered intravenously according to the frequency Q3W and different dosage of administration at different stages.AK104 is administered intravenously according to the frequency and dosage 10mg/kg Q3W.
Incidence and severity of adverse events(AE);
Incidence and severity of AEs is aim to evaluate the safety of AK127 and AK104
Incidence of serious adverse events(SAE);
Incidence of SAE is aim to evaluate the safety of AK127 and AK104.
Incidence of immune-related adverse events(irAE);
Incidence of irAE is aim to evaluate the safety of AK127 and AK104.
The incidence of suspected unexpected serious adverse reactions(SUSAR);
The incidence of SUSAR is aim to evaluate the safety of AK127 and AK104.
Objective response rate(ORR)
ORR is proportion of subjects with complete response(CR) or partial response(PR), based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1(Solid Tumor)or Lugano 2014 Evaluation Criteria(lymphoma).
Disease control rate(DCR)
Disease control rate(DCR) is defined as the proportion of subjects achieving a best of response(BOR) of confirmed CR and PR and stable disease(SD) per RECIST v1.1(Solid Tumor)or Lugano 2014 Evaluation Criteria(lymphoma).
duration of response(DoR)
Duration of response(DoR) is defined as the period from the first documentation of confirmed response(CR or PR) to the first documentation of progressive disease(PD) (as per RECIST v1.1(Solid Tumor)or Lugano 2014 Evaluation Criteria(lymphoma)) or death due to any cause, whichever occurs first.
time to response(TTR)
Time to response(TTR) is defined as the time from the first dose of investigational products until the first confirmation of CR or PR.
