This is a phase I, open-label, multi-center, dose escalation and expansion study in advanced or metastatic solid tumor patients. The're are two goals set in this study: one is to explore the safety and tolerability of KGX101 when mono and combo with envafolimab in Chinese patients, the other is to determine recommended phase 2 dose of KGX101 mono and combo with envafolimab. Participants will: 1. Take drug KGX101 mono or combo with envafolimab every 3 weeks; 2. Visit the clinic for checkups and tests. Schedule will be about 6-8 times in the first month and then about every 3 weeks afterwards.
Any histologically or cytologically confirmed solid tumor malignancy that is locally advanced or metastatic and has failed standard of care, no further standard can be used, or standard of care is not fit;
Eastern cooperative oncology grous performance status of 0-1;
Has at least 1 measurable lesion per RECIST 1.1;
Has adequate organ and bone marrow function as per study which including hemoglobin > 90 g/L, platelet count >=100*10e9/L, absolute meutrophil count >=1.5*10e9/L;
Active known second malignancy except adequately treated basal cell carcinoma, squamous cell skin cancer, in situ cervical cancer, breast cancer;
Patients with primary CNS malignancies;
Evidence of severe or uncontrolled systemic diseases, including: active infection, hypertension, chronically unhealed wound or ulcers;
Active autoimmnue disease requiring systemic treatment in the last 2 years, or immunodefiency which is on immunosuppressive therapy, chronic systemic or enteric steroid therapy;
Parallel
KGX101 injection
DrugKGX101 is a heterodimeric IL-12 prodrug with the C-terminus of IL-12 fused with ADCC-impaired IgG1 Fc and the N-terminus of IL-12 masked using the IL-12 binding domains of IL-12Rβ1 and IL-12Rβ2. KGX101 injection is a sterile, white or white-like lyophilized powder, supplied at 4.0 mg/vial for single use.
Envafolimab
DrugEnvafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment formulated for subcutaneous injection.
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Treatment groupsSee each treatment group below.
Numbers of participants with adverse events
AE will be collected to assess participants' safety after KGX101 monotherapy or combo with Envafolimab
Number of participants with dose limiting toxicities/DLT within DLT observation period
DLT will be observed from start of the first priming dose of KGX101 until 21 days post the first target dose of KGX101
Number of participants with changes of clinical lab abnormalities
Any changes in values of the clinical chemistry, hematology, coagulation and urinalysis will be evaluated
The maximum tolerated dose of KGX101 monotherapy and combination therapy with Envafolimab
PK parameters: Maximum Concentration (Cmax) of total IL-12
Part A- The PK schedule after the first and third target dose injection of KGX101 are as follows: pre-dose, 0 h, 2, 6, 24, 48, 72, 168 and 336hr post dose. Other sample collection timepoints include: pre-dose of each priming dose, pre-dose of other target dose; Part B- The PK schedule after Envafoliamb: pre-dose (1st, 2nd, 3rd and 4th treatment) and 72h ±1 h post the 1st Envafolimab treatment.
PK Parameters: Time of maximum observed concentration (Tmax)of total IL-12
Part A- The PK schedule after the first and third target dose injection of KGX101 are as follows: pre-dose, 0 h, 2, 6, 24, 48, 72, 168 and 336hr post dose. Other sample collection timepoints include: pre-dose of each priming dose, pre-dose of other target dose; Part B- The PK schedule after Envafoliamb: pre-dose (1st, 2nd, 3rd and 4th treatment) and 72h ±1 h post the 1st Envafolimab treatment.
PK Parameters: Area under the curve (AUC)
Part A- The PK schedule after the first and third target dose injection of KGX101 are as follows: pre-dose, 0 h, 2, 6, 24, 48, 72, 168 and 336hr post dose. Other sample collection timepoints include: pre-dose of each priming dose, pre-dose of other target dose; Part B- The PK schedule after Envafoliamb: pre-dose (1st, 2nd, 3rd and 4th treatment) and 72h ±1 h post the 1st Envafolimab treatment.
PK Parameters: Half- life (T1 /2)
Part A- The PK schedule after the first and third target dose injection of KGX101 are as follows: pre-dose, 0 h, 2, 6, 24, 48, 72, 168 and 336hr post dose. Other sample collection timepoints include: pre-dose of each priming dose, pre-dose of other target dose; Part B- The PK schedule after Envafoliamb: pre-dose (1st, 2nd, 3rd and 4th treatment) and 72h ±1 h post the 1st Envafolimab treatment.
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