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

Sponsor

Chimagen Biosciences, Ltd (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05348889

Collaborator

(none)

165

Enrollment

Locations

Arm

Anticipated Duration (Months)

82.5

Patients Per Site

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma (Disorder) Acute Lymphoid Leukemia, Disease (Disorder)	Drug: 1A46 Injection	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

165 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Preinduction salvage chemotherapy and ASCT should be considered 1 therapy.
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:

Topical, ocular, intra-articular, intranasal, or inhalational corticosteroids.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Norton Cancer Institute	Louisville	Kentucky	United States	40202-1840
2	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030-4000