A Phase 1, First-in-Human, Multicenter, Open-Label, Dose Escalation Trial of KGX101 Monotherapy and in Combination with Envafolimab in Patients with Advanced or Metastatic Solid Tumors.
Overview
- Phase
- Phase 1
- Intervention
- KGX101- Cohort -1
- Conditions
- Advanced or Metastatic Solid Tumors
- Sponsor
- Kangabio AUSTRALIA LTD PTY
- Enrollment
- 54
- Locations
- 3
- Primary Endpoint
- Number of participants with Treatment emergent Adverse events (TEAEs)
- Status
- Active, Not Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is an open label, two-part, multicenter, multi-regional phase I trial to investigate the safety, tolerability, and PK of KGX101 monotherapy and combination therapy with Envafolimab in patients with advanced or metastatic solid tumors.
Detailed Description
This study will enrol 54 participants depending on the number of dose escalations needed. The study has 2 parts- Part A monotherapy dose escalation and Part B combination dose escalation. This study will assess KGX101 monotherapy (Part A) and in combination therapy with Envafolimab (Part B) by a standard 3+3 dose escalation design to identify the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D). This study schedule will include a 28-day screening, a DLT observation period, followed by variable length study treatment period, 90-day safety follow-up after the last treatment, and survival follow-up every 90 days. Therefore, the total duration of participation will vary for each participant depending on total doses. A priming dose is the initial lower dose(s) followed by escalation to the full treatment dose(s). Priming dose will be implemented in all cohorts. As the first 3 enrolled previously participants at 0.003 mg/kg didn't receive priming dose, the subsequent enrolled patients at this dose level will receive two priming doses before the target dose. Two priming doses of KGX101 with an dosing interval of 10 days will be recommended. Priming dose regimen may be adjusted by Dose Escalation Committee (DEC) based on the real-time safety, available PK and PD data. The participants will receive KGX101 intravenous infusion at assigned escalating dose alone or in combined with 400mg Envafolimab every 3 weeks until disease progression or discontinuation criterion is met.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Part A: Any histologically or cytologically confirmed solid tumor malignancy that is locally advanced or metastatic and has failed standard therapy, or for which no further standard therapy exists.
- •Part B- In addition to above for Part B, participants should be tumor PD-L1 expression negative or with PD-L1 expression too low to fit for the immune checkpoint inhibitor treatment or have had disease progression after immune checkpoint inhibitor treatment.
- •Age at least 18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 -
- •Has at least 1 measurable lesion per RECIST 1.1 (lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions).
- •Has adequate organ and bone marrow function as per the study (blood transfusion or use of use hematopoietic stimulating factor for correction within 14 days are not permitted):
- •Hematologic: White blood cell (WBC) count ≥ 3 x 109/L; an absolute neutrophil count ≥ 1.5 x 109/L; a hemoglobin level \> 90 g/L; and a platelet count ≥ 100 x 109/L;
- •Adequate hepatic function as defined by:
- •Total bilirubin ≤ 1.5 times the ULN if no liver metastases or ≤ 2.5 times the ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases;
- •Aspartate transaminase (AST), alanine transaminase (ALT) and Alkaline phosphatase (ALP) levels ≤ 2.5 x the ULN or ≤ 5 x the ULN for patients with liver metastases;
Exclusion Criteria
- •Active known second malignancy with the exception of any of the following: adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ cervical cancer, breast cancer, papillary thyroid carcinoma; adequately treated stage I cancer from which the patient is currently in remission and has been in remission for ≥ 2 years; low risk prostate cancer with Gleason score \< 7 and prostate-specific antigen \<10ng/mL; any other cancer from which the patient has been disease-free survival for ≥ 5 years.
- •Patients with primary CNS malignancies.
- •A history of allogeneic tissue/solid organ transplant.
- •Any evidence of severe or uncontrolled systemic diseases, including:
- •Active, uncontrolled systemic bacterial, viral, or fungal infection;
- •uncontrolled hypertension (Systolic blood pressure more than equal to 160mHG or diastolic blod pressure more than equal to 100mm HG or poor compliance with anti-hypertensive agents;
- •or active bleeding diatheses;
- •Clinically significant arrhythmia, unstable angina pectoris, congestive heart failure (class III or IV of New York Heart Association \[NYHA\]) or acute myocardial infarction within 6 months;
- •Uncontrolled diabetes or poor compliance with hypoglycemic agents;
- •The presence of chronically unhealed wound or ulcers;
Arms & Interventions
KGX101- Cohort -1
Dosage level: Dose level 1 Dose form: White-like lyophilized powder Route of administration: Intravenous
Intervention: KGX101- Cohort -1
KGX101- Cohort 1
Dosage level: Dose level 2. Dose form: White-like lyophilized powder Route of administration: Intravenous
Intervention: KGX101- Cohort 1
KGX101- Cohort 2
Dosage level: Dose level 3 Dose form: White-like lyophilized powder Route of administration: Intravenous
Intervention: KGX101- Cohort 2
KGX101- Cohort 3
Dosage level: Dose level 4 Dose form: White-like lyophilized powder Route of administration: Intravenous
Intervention: KGX101- Cohort 3
KGX101- Cohort 4
Dosage level: Dose level 5 Dose form: White-like lyophilized powder Route of administration: Intravenous
Intervention: KGX101- Cohort 4
KGX101- Cohort 5
Dosage level: Dose level 6 Dose form: White-like lyophilized powder Route of administration: Intravenous
Intervention: KGX101- Cohort 5
KGX101 and Envafolimab
Part B combination therapy KGX101 with Envafolibmab. Dose form: Injection Route to administration: Injection
Intervention: KGX101 and Envafolimab
Outcomes
Primary Outcomes
Number of participants with Treatment emergent Adverse events (TEAEs)
Time Frame: From baseline to 30 days after the last dose administration.
TEAE will be collected to assess participants' safety after KGX101 treatment.
To estimate the Maximum tolerated dose of KGX101 monotherapy and combination therapy with Envafolimab.
Time Frame: From Day 1 after the first dose of KGX101 full treatment to D21 post dose.
Number of participants with Dose Limiting Toxicities (DLTs) at week 4
Time Frame: From Day 1 after the first dose of KGX101 full treatment to D21 post dose.
DLT will be observed from start of treatment until 21 days post the first target dose treatment.
Number of participants with changes to clinical laboratory abnormalities
Time Frame: Screening to 90 days post last dose administration
Any changes in values of the clinical chemistry, hematology, coagulation and urinalysis will be evaluated.
Secondary Outcomes
- PK Parameters- Trough concentration (Ctrough)(Part A- From pre-dose of the first dose of KGX101 full treatment to Day 90 after the first and 4th dose of full treatment; Part B- Predose and 72hrs (only 1st treatment))
- Immunogenicity- Anti-drug antibody (ADA)(Part A- From pre-dose of the first dose of KGX101 full treatment to Day 90 hours after the first and 4th dose of full treatment; Part B- Predose and 72hrs (only 1st treatment))
- Number of participants with changes in the Investigator-assessed confirmed Best Overall Response (BOR)(From Day 1 after the first dose of KGX101 full treatment to D21 post dose.)
- PK Parameters: Maximum Concentration (Cmax)(Part A- From pre-dose of the first dose of KGX101 full treatment to Day 90 after the first and 4th dose of full treatment; Part B- Predose and 72hrs (only 1st treatment))
- PK Parameters: Time of maximum observed concentration (Tmax)(Part A- From pre-dose of the first dose of KGX101 full treatment to Day 90 after the first and 4th dose of full treatment; Part B- Predose and 72hrs (only 1st treatment))
- PK Parameters: Half- life (T1 /2)(Part A- From pre-dose of the first dose of KGX101 full treatment to Day 90 after the first and 4th dose of full treatment; Part B- Predose and 72hrs (only 1st treatment))
- PK Parameters: Area under the curve (AUC)(Part A- From pre-dose of the first dose of KGX101 full treatment to Day 90 after the first and 4th dose of full treatment; Part B- Predose and 72hrs (only 1st treatment))
- Number of participants with changes in the Overall Response (ORR)(From Day 1 after the first dose of KGX101 till survival follow-up every 90 days post last treatment.)
- Progression free survival (PFS) per RECIST 1.1(From Day 1 after the first dose of KGX101 till survival follow-up every 90 days post last treatment.)
- Overall survival(From Day 1 after the first dose of KGX101 till survival follow-up every 90 days post last treatment.)
- Change in serum concentration of KGX101 and total IL-12(From Day 1 after the first dose of KGX101 till survival follow-up every 90 days post last treatment.)
- PK Parameters- Systemic clearance (CL)(Part A- From pre-dose of the first dose of KGX101 full treatment to Day 90 after the first and 4th dose of full treatment; Part B- Predose and 72hrs (only 1st treatment))
- PK Parameters- Volume of distribution (Vd)(Part A- From pre-dose of the first dose of KGX101 full treatment to Day 90 hours after the first and 4th dose of full treatment; Part B- Predose and 72hrs (only 1st treatment))