A Study of ATG-031 in Advanced Solid Tumors or B-cell Non-Hodgkin Lymphomas

Sponsor

Antengene Biologics Limited (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06028373

Collaborator

(none)

Enrollment

Arm

32.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

ATG-031 study (alias: PERFORM) is a multicenter, open-label, Phase 1 study of ATG-031 in patients with advanced solid tumors or B-NHL. The study design includes a Dose Escalation Phase and a Dose Expansion Phase, and will enroll patients with advanced solid tumors (i.e., preferred tumor types) or relapsed/refractory (R/R) B-NHLs. The study's primary objective is to evaluate the safety and tolerability of ATG-031 and determine the RP2D of ATG-031.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors B-cell Non-Hodgkin Lymphomas	Drug: ATG-031	Phase 1

Detailed Description

This is a multicenter, open-label, Phase 1 study of ATG-031 in patients with advanced solid tumors or B-NHL. The study design includes a Dose Escalation Phase and a Dose Expansion Phase. Dose Escalation Phase: approximately 30-48 patients . Dose Expansion Phase: the number of patients enrolled will depend on the number of disease cohorts to be expanded and data observed in the Dose Escalation Phase.The Dose Escalation Phase will enroll patients with advanced solid tumors. Based on data from dose escalation (e.g., adverse events [AEs], dose-limiting toxicity [DLT], efficacy data, pharmacodynamic [PDx] data, or pharmacokinetic [PK] data), the Dose Expansion Phase will enroll patients with selected advanced solid tumors or B-NHL.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Dose levels are 0.03 mg/kg、 0.1 mg/kg、0.3 mg/kg 、1.0 mg/kg 、2.0 mg/kg、4.0 mg/kg 、6.0 mg/kg 、9.0 mg/kgDose levels are 0.03 mg/kg、 0.1 mg/kg、0.3 mg/kg 、1.0 mg/kg 、2.0 mg/kg、4.0 mg/kg 、6.0 mg/kg 、9.0 mg/kg

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A First-in-Human Phase I Study of ATG-031 in Patients With Advanced Solid Tumors or B-cell Non-Hodgkin Lymphomas

Anticipated Study Start Date :

Oct 13, 2023

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Jun 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ATG-031 Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase. Dose levels are 0.03 mg/kg、 0.1 mg/kg、0.3 mg/kg 、1.0 mg/kg 、2.0 mg/kg、4.0 mg/kg 、6.0 mg/kg 、9.0 mg/kg.	Drug: ATG-031 ATG-031 will be infused Q3W on Day 1 of each cycle, at the starting dose of 0.03 mg/kg and a maximum dose of 9 mg/kg in the Dose Escalation Phase, and the defined MTD if available or OBD in the Dose Expansion Phase. Based on the emerging PK, PDx, safety, and other relevant data, SRC may decide to explore alternative dosing schedules.

Arm

Intervention/Treatment

Experimental: ATG-031

Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase. Dose levels are 0.03 mg/kg、 0.1 mg/kg、0.3 mg/kg 、1.0 mg/kg 、2.0 mg/kg、4.0 mg/kg 、6.0 mg/kg 、9.0 mg/kg.

Drug: ATG-031

ATG-031 will be infused Q3W on Day 1 of each cycle, at the starting dose of 0.03 mg/kg and a maximum dose of 9 mg/kg in the Dose Escalation Phase, and the defined MTD if available or OBD in the Dose Expansion Phase. Based on the emerging PK, PDx, safety, and other relevant data, SRC may decide to explore alternative dosing schedules.

Outcome Measures

Primary Outcome Measures

AE [90 days after last dose of treatment]
Evaluate the safety and tolerability of ATG-031
DLT [at the end of cycle 2 ( each cycle is 21 days)]
Evaluate the safety and tolerability of ATG-031
RP2D [at the end of dose escalation, about 1 year]
RP2D will be determined based on safety, tolerability, PK, and preliminary efficacy data

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Histological or cytologically confirmed advanced solid tumor or B-NHL which have relapsed from or been refractory to all locally available standard therapies.
Adequate hepatic function:
AST and ALT ≤ 2.5×times ULN (≤ 5 × ULN if liver metastases).
Total bilirubin ≤ 1.5×ULN (except Gilbert syndrome).
Lipase and amylase ≤ 2×ULN.
Adequate renal function: calculated creatinine clearance of ≥ 40 mL/min using the Cockroft- Gault formula.
Adequate bone marrow function without growth factors or blood transfusion within 7 days of the first dose of study treatment.
Absolute neutrophil count (ANC) ≥ 1.5×109/L.
Platelet count ≥ 100×109/L.
Hemoglobin ≥ 90 g/L.

Key Exclusion Criteria:

Patients with CNS malignancies, except those who are clinically stable for ≥ 4 weeks and off corticosteroids following prior surgery, whole-brain radiation, or stereotactic radiosurgery.
Received any other investigational product or prior systemic anticancer therapy including chemotherapy, immunotherapy, radiotherapy, or other anticancer within 21 days prior to first dose of study
Grade ≥3 irAEs or irAEs that lead to discontinuation of prior immunotherapy.8. Other primary malignancies developed within 5 years prior to the first dose of the study treatment
Other primary malignancies developed within 5 years prior to the first dose of the study treatment
Have active or previous autoimmune diseases that are likely to recur or are at risk of such diseases judged by the investigator.
Major cardiovascular disease
Active hepatitis B and/or hepatitis C (HBV-DNA or HCV-RNA detectable by local laboratory, respectively).
Patients with history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
A history of allograft organ transplantation for solid tumor or allogeneic hematopoietic stem cell transplantation for B-NHL patients).
Patients who are pregnant or lactating.