First-in-Human (FIH) Trial of 1A46 in Subjects With Advanced CD20 and/or CD19 Positive B-cell Hematologic Malignancies

A Phase 1/2, First in Human, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Triple-specific T-cell Engager 1A46 in Adult Patients With Advanced CD20 and/or CD19 Positive B-cell Hematologic Malignancies

This study will evaluate the safety and efficacy of 1A46 in adult patients with advanced CD20 and/or CD19 positive B-cell non-Hodgkin's lymphoma (NHL) or acute lymphoblastic leukemia (ALL).

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin's Lymphoma (Disorder); Acute Lymphoid Leukemia, Disease (Disorder)
• Intervention / Treatment: Drug: 1A46 Injection

Detailed Description

This study is an open-label, multicenter, 2-part study of 1A46 in adult patients with advanced relapsed/refractory (r/r) CD20 and/or CD19 positive B-cell non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (ALL) who do not have effective standard treatment available. This FIH study will include a dose escalation part and a dose expansion part in 4 cohorts.

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Trial Information; Phone Number: +862158325080; Email: trials@chimagen.com

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510-3220
      • Recruiting
      • Yale New Haven Hospital
      • Contact: Iris Isufi, M.D.; Phone Number: 203-737-5751; Email: iris.isufi@yale.edu
      • Contact: Julie Lecco; Email: Julie.lecco@yale.edu
  • Kentucky
    • Louisville, Kentucky, United States, 40202-1840
      • Recruiting
      • Norton Cancer Institute
      • Contact: Don Stevens, M.D.; Phone Number: 502-899-3366; Email: don.stevens@nortonhealthcare.org
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232-1309
      • Recruiting
      • Upmc Cancercenter
      • Contact: Alison Sehgal, M.D.; Phone Number: 412-235-1020; Email: sehgalar@upmc.edu
      • Contact: Amy Roger; Phone Number: (412) 623-4036; Email: rodgera@upmc.edu
  • Texas
    • Houston, Texas, United States, 77030-4000
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Sairah Ahmed, M.D.; Phone Number: 713-792-2860; Email: sahmed3@mdanderson.org
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Recruiting
      • Froedtert & the Medical College of Wisconsin Froedtert Hospital
      • Contact: Mehdi Hamadani, M.D.; Phone Number: 414-805-0643; Email: mhamadani@mcw.edu
      • Contact: Ashley White; Phone Number: (414) 805-8984; Email: aswhite@mcw.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Dose Escalation Part:

Aggressive NHL Patients：

• Aggressive NHL including mantle cell lymphoma and DLBCL histologies, NOS and/or BCL2, BCL6, and or MY B-cell lymphoma with intermediate features between DLBCL, FL grade 3B, and aggressive B-cell lymphoma unclassifiable
• have previously R-CHOP, R-EPOCH or equivalent anti-CD20 containing therapy
• with ≥ 2 prior lines of systemic therapy
• received or ineligible for autologous stem cell transplant (ASCT)
• have received or been intolerant of all other standard therapies thought to confer clinical benefit.

Indolent NHL Patients:

• including FL of Grades 1-3A and marginal zone lymphoma (MZL)
• refractory or relapsed after ≥ 2 prior lines of systemic therapy who have received or been intolerant of all other standard therapies thought to confer clinical benefit.
• Patients must require systemic therapy based on disease-specific criteria.

NHL patients should meet the following requirements:

• The following considerations pertain to prior treatment regimens for NHL:

  1. Preinduction salvage chemotherapy and ASCT should be considered 1 therapy.
  2. Patients with gastric extranodal MZL, should have failed H. pylori eradication therapy (when H. pylori positive).
• NHL patients must have expression of CD20 and/or CD19-expression
• NHL patients in the dose escalation part of the study must have ≥ 1 measurable target lesion as defined by Lugano 2014 criteria ALL Patients：

Ph-positive or Ph-negative B-cell ALL refractory to or relapsed after frontline treatment and 1 salvage regimen, have received or been intolerant of all other standard therapies thought to confer clinical benefit. ALL patients should meet the following requirements:

• Relapsed after or not a candidate for allogeneic SCT.
• No active acute or chronic graft-versus-host disease for 2 months prior to enrollment and currently receiving no immunosuppressive therapy.
• persistent CD19 staining of ≥ 50% of blasts.

Exclusion Criteria:

• Patient has brain metastasis or other significant neurological conditions.
• Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period.
• Active serious infection requiring antibiotics within 14 days before study entry.

• Treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or immunosuppressive medication ≤ 7 days before the first dose of 1A46, with the following exceptions:

  1. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroids.
  2. Dexamethasone used to reduce peripheral blast counts in ALL patients.
• Active hepatitis B or C.
• Known human immunodeficiency virus (HIV) infection.
• Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
• Cerebrovascular accident, transient ischemic attack, myocardial infarction, unstable angina, or New York Heart Association class III or IV heart failure < 6 months of study entry; uncontrolled arrhythmia < 3 months of study entry.
• Major surgery < 4 weeks or minor surgery < 2 weeks prior to screening.
• Live virus vaccines < 30 days prior to screening.
• Inflammatory chronic diseases, or any other diseases the investigator considers can be exacerbated in the setting of immune activation.
• History of Grade 3-4 allergic reaction to treatment with another mAb, or known to be allergic to protein drugs or recombinant proteins or excipients in 1A46 drug formulation.
• Active infection with coronavirus disease 2019 (COVID-19). Patients who have quarantined and have a negative test for virus may enroll.
• Concurrent malignancy < 5 years prior to entry other than adequately treated cervical carcinoma in situ, localized squamous cell cancer of the skin, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, or < T1 urothelial carcinoma.
• History of Grade 3-4 immune-related adverse events (irAEs) or irAEs requiring discontinuation of prior therapies.
• Pleural effusion, pericardial effusion or ascites requiring frequent drainage or medical intervention.
• QTc > 480 msec using Fredericia's QT correction formula
• Patients in the dose escalation part who weigh < 40 kg.

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: Dose Escalation; Open label, single arm trial where 1A46 will be administered	Drug: 1A46 Injection; Participants will receive IV 1A46 weekly for Cycles 1-8, then every 3 weeks (Q3W) for Cycles 9-16 (21 days/cycle).; Other Names: CMG1A46

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Escalation: Incidence of Adverse Events	To assess the safety and tolerability of 1A46	Adverse Events are assessed during the first cycle (28 days) in each cohort
Escalation: Dose liming toxicity (DLT)	To identify the RP2D and the MTD, if reached	DLTs are assessed during the first cycle (28 days) in each cohort

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Escalation: Maximum observed concentration (Cmax)	To characterize the PK properties of 1A46	At enrollment and at multiple timepoints until treatment discontinuation, assessed up to 1 year
Escalation: Time to reach Cmax (Tmax)	To characterize the PK properties of 1A46	At enrollment and at multiple timepoints until treatment discontinuation, assessed up to 1 year
Escalation: Area Under the Concentration-Time Curve (AUC) from Time 0 to t	To characterize the PK properties of 1A46	At enrollment and at multiple timepoints until treatment discontinuation, assessed up to 1 year
Escalation: Area under the serum concentration-time curve from time 0 to infinity (AUCinf)	To characterize the PK properties of 1A46	At enrollment and at multiple timepoints until treatment discontinuation, assessed up to 1 year
Escalation: Terminal disposition phase half-life(t1/2)	To characterize the PK properties of 1A46	At enrollment and at multiple timepoints until treatment discontinuation, assessed up to 1 year
Escalation: Total clearance after IV administration (CL)	To characterize the PK properties of 1A46	At enrollment and at multiple timepoints until treatment discontinuation, assessed up to 1 year
Escalation: Anti-drug antibody (ADA)	To characterize the PK properties of 1A46	From Baseline up to end of study or discontinuation due to disease progression, up to 5 years
Escalation: Objective Response Rate (ORR)	To evaluate preliminary anti-tumor efficacy of 1A46	From Baseline up to end of study or discontinuation due to disease progression, up to 5 years
Escalation: Disease control rate (DCR)	To evaluate preliminary anti-tumor efficacy of 1A46	From Baseline up to end of study or discontinuation due to disease progression, up to 5 years
Escalation: Progression free survival (PFS)	To evaluate preliminary anti-tumor efficacy of 1A46	From Baseline up to end of study or discontinuation due to disease progression, up to 5 years
Escalation: Overall survival (OS)	To evaluate preliminary anti-tumor efficacy of 1A46	From Baseline up to end of study or discontinuation due to disease progression, up to 5 years

Collaborators and Investigators

• Sponsor: Chimagen Biosciences, Ltd
• Investigators: Study Director: Clinical Trial Management, Chimagen Biosciences, Ltd

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Lymphoma; Hematologic Neoplasms; Disease; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: CMG1A46-US01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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