A Study of ATG-010 in Combination With ATG-008 in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (MATCH)

An Open Label, Phase Ⅰb Study of ATG-010 in Combination With ATG-008 in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)

This is an Open label, Phase Ⅰb Study of ATG-010 in Combination With ATG-008 in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)

Study Overview

• Status: Terminated
• Conditions: Relapsed/Refractory Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Combination product: ATG-010 and ATG-008

Detailed Description

This is a multi-center, open label, phase 1 study conducted in RR DLBCL patients. The MTD and/or RP2D of study treatment, ATG-010 in combination with ATG-008, will be selected using BOIN design for the dose escalation phase. Additional patients will be enrolled as an expansion cohort after MTD and/or RP2D is determined.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Stephanie Zou; Phone Number: 166 1993 0254; Email: stephanie.zou@antengene.com
• Study Contact Backup: Name: Ran Wei; Phone Number: 13810001510; Email: ran.wei@antengene.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410029
      • Hunan Cancer hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Affiliated Hospital of China Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years old.
2. ECOG Performance score of ≤2.
3. Estimated life expectancy of >3 months.
4. Previously treated, pathologically confirmed DLBCL

5. Patients must have received at least 2 but no more than 5 previous systemic regimens (for non-DH/TH, non-DE DLBCL and DLBCL not transformed from FL or CLL), or at least 1 but no more than 5 previous systemic regimens (for DH/TH, DE DLBCL, and DLBCL transformed from FL or CLL) for the treatment of their DLBCL.

   1. Prior stem cell transplantation is allowed; induction, consolidation, stem cell collection, preparative regimen and transplantation ± maintenance are considered a single line of therapy.
   2. Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of therapy.
   3. Any maintenance therapy will not be counted as a separate line of systemic therapy.
   4. Radiation with curative intent for localized DLBCL will not be counted as 1 line of therapy
6. Documented radiographic evidence of progressive DLBCL of the last line (or refractory DLBCL) prior to the first dosing.

Exclusion Criteria:

1. Female patients who are pregnant or lactating
2. DLBCL with mucosa-associated lymphoid tissue [MALT] lymphoma, or primary mediastinal (thymic) large B-cell lymphoma (PMBL)
3. Known central nervous system lymphoma or meningeal involvement (for dose expansion phase, patients with stable CNS disease could be considered).
4. Patients eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (the Investigator must provide detailed documentation for ineligibility)
5. Use of any standard or experimental anti-DLBCL therapy (including radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to Cycle 1 Day 1.
6. Autologous stem cell transplant (SCT) <6 months or prior allogeneic SCT, or CAR-T cell infusion <6 months prior to Cycle 1.
7. Major surgery within 4 weeks of the first dose of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ATG-010 and ATG-008; ATG-010 and ATG-008 should be taken 6 hours apart on a PK sampling day

Combination product: ATG-010 and ATG-008; Patients enrolled will receive consecutive daily treatment at assigned dose level. The starting dose of ATG-010 at the dose escalation phase will be 60 mg QW, which could be escalated to 80 mg QW, 100 mg QW, 60 mg BIW. In case 60 mg QW of ATG-010 with any dose of ATG-008 is NOT tolerable, 40 mg QW ATG-010 could be explored. The starting dose of ATG-008 will be 15 mg QD, which could be escalated to 20 mg QD, with maximum of 30 mg QD. SRC will be consulted before each dose escalation starts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	Maximum Tolerated Dose	the last patient on study has completed 12 months of follow-up
RP2D	Recommended Phase 2 Dose	the last patient on study has completed 12 months of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall Response Rate	the last patient on study has completed 12 months of follow-up
PFS	Progression Free Survival	the last patient on study has completed 12 months of follow-up
DOR	Duration of Response	the last patient on study has completed 12 months of follow-up
OS	Overall Survival	the last patient on study has completed 12 months of follow-up
TTR	Time To Response	the last patient on study has completed 12 months of follow-up
TTP	Time To Progression	the last patient on study has completed 12 months of follow-up

Collaborators and Investigators

• Sponsor: Antengene Corporation
• Investigators: Study Director: Yang Yu, Medical Monitor

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Actual): February 6, 2023
• Study Completion (Actual): February 8, 2023

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Lymphoma, Hodgkin's lymphoma , non-Hodgkin's lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: ATG-008&010-DLBCL-001

Drug and device information, study documents

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