A Phase I Study to Investigate the Safety and Tolerability of KGX101 Monotherapy and Combination Therapy With Envafolimab in Advanced or Metastatic Solid Tumor Patients

A Phase I , Open Label, Multi-center Study to Assess the Safety and Tolerability of KGX101 Mono and Combo Therapy With Envafolimab in Advanced or Metastatic Solid Tumor Patients

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: KGX101 injection; Drug: Envafolimab

• Study Type: Interventional
• Enrollment (Estimated): 57
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jun Guo; Phone Number: 13911233048; Email: guoj307@126.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Principal Investigator: Jun Guo
      • Contact: Director Jiang; Phone Number: +86-010-88197746; Email: gcp_jiangm@bjcancer.org
      • Contact: Email: guoj307@126.com
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Principal Investigator: Hongxia Wang, MD
      • Contact: Che Li; Phone Number: +86-021-38196379; Email: Junqian@fudan.edu.cn
    • Shanghai, Shanghai Municipality, China, 200433
      • Recruiting
      • Shanghai Chest Hospital
      • Principal Investigator: Shun Lu, MD
      • Contact: Yu Feng, MD; Phone Number: 7085 +86-021-22200000; Email: xkyyGCP2021@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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;
2. Eastern cooperative oncology grous performance status of 0-1;
3. Has at least 1 measurable lesion per RECIST 1.1;
4. 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;
5. Life expectancy of at least 3 months;
6. Provision of signed and dated written inform consent prior to any study-related procedures, sampling and analyses.

Exclusion Criteria:

1. Active known second malignancy except adequately treated basal cell carcinoma, squamous cell skin cancer, in situ cervical cancer, breast cancer;
2. Patients with primary CNS malignancies;
3. Evidence of severe or uncontrolled systemic diseases, including: active infection, hypertension, chronically unhealed wound or ulcers;
4. Active autoimmnue disease requiring systemic treatment in the last 2 years, or immunodefiency which is on immunosuppressive therapy, chronic systemic or enteric steroid therapy;
5. History of pneumonitis, interstitial lung disease which require steroids or has current pneumonitis/ interstitial lung disease;
6. Any unresolved toxicities from prior therapy greater than CTCAE 5.0 grade 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KGX101 monotherapy-Dose level 1	Drug: KGX101 injection; KGX101 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.
Experimental: KGX101 monotherapy-Dose level 2	Drug: KGX101 injection; KGX101 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.
Experimental: KGX101 monotherapy-Dose level 3	Drug: KGX101 injection; KGX101 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.
Experimental: KGX101 monotherapy-Dose level 4	Drug: KGX101 injection; KGX101 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.
Experimental: KGX101 monotherapy dose expansion	Drug: KGX101 injection; KGX101 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.
Experimental: KGX101 combo with Envafolimab-Dose level 1	Drug: KGX101 injection; KGX101 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.; Drug: Envafolimab; Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment formulated for subcutaneous injection.
Experimental: KGX101 combo with Envafolimab-Dose level 2	Drug: KGX101 injection; KGX101 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.; Drug: Envafolimab; Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment formulated for subcutaneous injection.
Experimental: KGX101 combo with Envafolimab-Dose level 3	Drug: KGX101 injection; KGX101 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.; Drug: Envafolimab; Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment formulated for subcutaneous injection.
Experimental: KGX101 combo with Envafolimab dose expansion	Drug: KGX101 injection; KGX101 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.; Drug: Envafolimab; Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment formulated for subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numbers of participants with adverse events	AE will be collected to assess participants' safety after KGX101 monotherapy or combo with Envafolimab	From baseline to 30 days after the last dose administration.
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	From Day1 after the first priming dose of KGX101 until 21 days post the first target dose ofKGX101
Number of participants with changes of clinical lab abnormalities	Any changes in values of the clinical chemistry, hematology, coagulation and urinalysis will be evaluated	From screening until 90 days post the last dose administration
The maximum tolerated dose of KGX101 monotherapy and combination therapy with Envafolimab		From Day 1 post the first dosing until 21 days post the the first target dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.	Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.
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.	Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.
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.	Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.
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.	Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.
PK Parameters- Trough concentration (Ctrough)	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.	Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.
PK Parameters- Systemic clearance (CL)	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.	Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.
PK Parameters- Volume of distribution (Vd)	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.	Part A: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until Day 1 of the last dose.
Immunogenicity- Anti-drug antibody (ADA)	Samples will be collected to assess the immunogeniccity after each KGX101 treatment.	Part A: From pre-dose of the first dose of KGX101 treatment until 90 days afrer the last dose. Part B: From pre-dose of the first dose of KGX101 treatment until 90 days after the last dose.
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 the last treatment.

Collaborators and Investigators

• Sponsor: Kangabio AUSTRALIA LTD PTY
• Investigators: Principal Investigator: Jun Guo, Beijing Cancer Hopspital

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): December 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: envafolimab
• Other Study ID Numbers: KGX101ST102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No