Trial Title:
This is an Open Label, Two-part, Multicenter, 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.
NCT ID:
NCT06074497
Condition:
Advanced or Metastatic Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
KGX101- Cohort -1
Description:
Single dose of 0.1, 0.3, 1μg/kg of KGX101 every 3 weeks
Arm group label:
KGX101- Cohort -1
Intervention type:
Drug
Intervention name:
KGX101- Cohort 1
Description:
Single dose of 0.3, 1.0, 3.0μg/kg of KGX101 every 3 weeks
Arm group label:
KGX101- Cohort 1
Intervention type:
Drug
Intervention name:
KGX101- Cohort 2
Description:
Single dose of 1, 1 and 3μg/kg of KGX101 every 3 weeks
Arm group label:
KGX101- Cohort 2
Intervention type:
Drug
Intervention name:
KGX101- Cohort 3
Description:
Single dose of 1,3 and 6μg/kg of KGX101 every 3 weeks
Arm group label:
KGX101- Cohort 3
Intervention type:
Drug
Intervention name:
KGX101- Cohort 4
Description:
Single dose of 1,3,12μg/kg of KGX101 every 3 weeks
Arm group label:
KGX101- Cohort 4
Intervention type:
Drug
Intervention name:
KGX101- Cohort 5
Description:
Single dose of 2, 5 and 15 μg/kg of KGX101 every 3 weeks
Arm group label:
KGX101- Cohort 5
Intervention type:
Drug
Intervention name:
KGX101 and Envafolimab
Description:
Part B combination therapy KGX101 with Envafolibmab. 400mg to be injected subcutaneously
with each target dose of KGX101 every 3 weeks. The dose escalation committee (DEC) may
decide to increase the dosage to 600mg. based on PK, PD and safety data.
Arm group label:
KGX101 and Envafolimab
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. Age at least 18 years.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1.
4. 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).
5. 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):
1. 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;
2. 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;
- Coagulation international normalized ratio (INR) and activated partial
thromboplastin time (aPTT) ≤ 1.5 x the ULN;
3. Adequate renal function as defined by a serum creatinine ≤ 1.5 times the ULN
concurrent with creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft--
Gault equation);
4. Biochemistry: albumin ≥ 3.0g/dL
6. Willingness of men and women of reproductive potential to observe highly effective
birth control for the duration of treatment and for 5 months following the last dose
of study drug.
7. Paired pre-treatment archival tumor tissue within two years or fresh tumor biopsy
and on-treatment fresh tumor biopsy will be optional. For participants of cutaneous
malignant melanoma, paired pre-treatment archival tumor tissue and on-treatment
fresh tumor biopsy should be mandatory
8. Life expectancy of approximately 3 months or longer in the opinion of the
Investigator.
9. Provision of signed and dated written informed consent prior to any study-specific
procedures, sampling, and analyses.
Exclusion Criteria:
1. 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.
2. Patients with primary CNS malignancies.
3. A history of allogeneic tissue/solid organ transplant.
4. Any evidence of severe or uncontrolled systemic diseases, including:
1. Active, uncontrolled systemic bacterial, viral, or fungal infection;
2. 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;
3. or active bleeding diatheses;
4. 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;
5. Uncontrolled diabetes or poor compliance with hypoglycemic agents;
6. The presence of chronically unhealed wound or ulcers;
7. Other chronic diseases, which, in the opinion of the Investigator, could
compromise safety of the patient or the integrity of study.
5. Active autoimmune disease requiring systemic treatment in the past 2 years.
6. Diagnosis of immunodeficiency, is on immunosuppressive therapy, or is receiving
chronic systemic or enteric steroid therapy.
7. A history of (non-infectious) pneumonitis / interstitial lung disease that required
steroids or has current pneumonitis / interstitial lung disease.
8. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric
Castleman Disease.
9. Active infection as determined by hepatitis B surface antigen and hepatitis B core
antigen antibody, or hepatitis B virus DNA by quantitative polymerase chain reaction
(qPCR) testing.
10. Active infection as determined by hepatitis C virus (HCV) antibody or HCV RNA by
qPCR testing.
11. Major surgery (excluding placement of vascular access) within 4 weeks prior to the
first dose of study drug.
12. Treatment with any of the following:
1. Prior treatment with IL-12 therapy (any form, e.g. recombinant human, prodrug,
intratumoral, etc.);
2. Presence of CNS metastases that are symptomatic and/or require local CNS
directed therapy (such as XRT or surgery) or increasing doses of
corticosteroids within 2 weeks prior to the first dose of study drug. Except
patients with treated brain metastases should be neurologically stable and
receiving less than equal to 10mg per day of prednisone or equivalent prior to
study entry;
3. Investigational agent or anticancer therapy (including chemotherapy, biologic
therapy, immunotherapy, anticancer Chinese medicine, or anticancer herbal
remedy) within 5 half-lives or 4 weeks (whichever is shorter) prior to the
first dose of study drug;
4. Radiotherapy within 2 weeks of the start of study treatment. A 1-week washout
is permitted for palliative radiation (less than equal to two weeks of
radiotherapy) to non-CNS disease;
5. Received a live or live-attenuated vaccine within 30 days of the first dose of
study drug; Note: Administration of killed vaccines or other formats are
allowed;
6. Diagnosis of immunodeficiency, on immunosuppressive therapy, or receiving
chronic systemic or enteric steroid therapy (dose > 10 mg/day of prednisone or
equivalent);
7. Prior receipt of an allogeneic stem cell transplant or allogeneic CAR-T cell
therapy;
13. Any unresolved toxicities from prior therapy greater than NCI CTCAE version 5.0
Grade 1 at the time of starting study drug with the exception of alopecia and Grade
2 prior platinum-therapy related neuropathy, and medical history conditions
requiring maintenance therapy such as, but not limited to, hypothyroidism and
adrenal insufficiency, where the principal investigator (PI) has the discretion to
determine the appropriate severity classification at study screening, contingent
upon the patient's screening labs not showing clinically significant abnormalities
and meeting the eligibility requirements as per sponsor and site PI approval.
14. Electrocardiogram QT interval corrected for heart rate (QTc) > 470 msec, measured by
Fridericia's formula [QTcF=QT/(RR0.33)]; or any of the following cardiac events
within 6 months before screening: Myocardial infarction; unstable angina; unstable
symptomatic ischemic heart disease; New York Heart Association class III or IV heart
failure; Thromboembolic events (eg, pericardial effusion, restrictive
cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart
disease).
15. Any illness, medical condition, organ system dysfunction, or social situation
(including mental illness or substance abuse), that may interfere with a patient's
ability to sign the ICF, adversely affect the patient's ability to cooperate and
participate in the study, or compromise interpretation of study results.
16. Pregnant (confirmed by serum beta human chorionic gonadotropin [ HCG]) or lactating.
17. History of hypersensitivity to any of the study drug components; or history
experienced grade ≥ 3 irAEs and leads to permanent discontinuation in prior
immunotherapy.
18. Part B: participants who are not tolerant to immune checkpoint inhibitor therapy.
19. Participant is known or suspected of not being able to comply with the study
protocol (e.g. because of alcoholism, drug dependency, or psychological disorder) or
the participant has any condition for which, in the opinion of the Investigator,
participation in the study would not be in the best interest of the participant
(e.g. compromise their well-being) or that could prevent, limit, or confound the
protocol-specified assessments. Or any other disease or clinically medical status
that the investigator considers the patient is unstable or may affect their safety
or study compliance.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Pindara Private Hospital
Address:
City:
Benowa
Zip:
4217
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Andrea Tazbirkova, Dr
Phone:
0755971211
Email:
tazbirkova@yahoo.com.au
Facility:
Name:
Sunshine Coast University Private Hospital
Address:
City:
Birtinya
Zip:
4575
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Michelle Morris, Dr
Phone:
0408705286
Email:
morrismi2@ramsayhealth.com.au
Facility:
Name:
Peninsula & South Eastern Haematology and Oncology Group
Address:
City:
Frankston
Zip:
3199
Country:
Australia
Status:
Completed
Start date:
December 13, 2023
Completion date:
May 30, 2026
Lead sponsor:
Agency:
Kangabio AUSTRALIA LTD PTY
Agency class:
Industry
Source:
Kangabio AUSTRALIA LTD PTY
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06074497
