Phase I/II Clinical Study of 1A46 Drug Substance

NCT05987605 | Terminated Phase 1 DMC

• 1 other identifier: BR110-I/II
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

A phase I/II, first in human, single arm, open label study to evaluate the safety and efficacy of the injection of triple-specific T-cell engager 1A46 in adult subjects with R/R CD20 positive and/or CD19 positive B cell non-Hodgkin's lymphoma (B - NHL)

Conditions

Advanced Malignancies

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicity (DLT) (Phase I)

  Number of subjects with a DLT

  Up to 4 weeks

• Maximum tolerated dose (MTD) (Phase I)

  Determine maximum tolerated dose (MTD) of BR110

  Up to 4 weeks

• Recommended phase 2 dose (RP2D) (Phase I)

  Determine recommended phase 2 dose (RP2D) of BR110.

  Up to 48 weeks

• Objective response rate (ORR) (Phase II)

  he primary efficacy outcome is ORR(CR+PR), measured per Lugano 2014 Classification for Lymphomas

  Up to 48 weeks

Secondary Outcomes (7)

• Number of subjects with adverse events (Phase Ia)

  Up to 48 weeks

• Pharmacokinetic concentration

  Up to 48 weeks

• Immunogenicity

  Up to 48 weeks

• Disease Control Rate (DCR）

  Up to 48 weeks

• Progression-Free Survival (PFS)

  Up to 48 weeks

Other Outcomes (4)

• Exploratory Objectives(Phase I)

  Up to 48 weeks

• Exploratory Objectives(Phase I)

  Up to 48 weeks

• Exploratory Objectives(Phase I)

  Up to 48 weeks

Study Arms (1)

1A46 Drug Substance

EXPERIMENTAL

One cycle is defined as 21 days. Patients will be scheduled to receive weekly infusions of 1A46 for the first cycle and then for the remaining 15 cycles of the study, patients will receive a single infusion of 1A46 per cycle (Q3W)

Drug: 1A46 Drug Substance

Interventions

1A46 Drug Substance DRUG

Cycle 1 which will consist of an initial dose given on C1D1 and an intermediate dose given on C1D8, followed by a maintenance dose beginning on C1D15 and continuing while the patient is treated at that dose level

1A46 Drug Substance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Male or female patients aged 18 years or older; 2. Be able to sign informed consent form voluntarily and understand the study, incuding the purpose and the procedure and be able to comply with protocol requirements; 3. Patient populations:
• Dose Escalation:
• Aggressive NHL (aNHL) : MCL, each subtype of DLBCL and FL3b, PMBCL, high level of B cell lymphoma, etc.
• Indolent NHL (iNHL) : including FL1-3 a grade, MZL, small lymphocytic lymphoma, etc.
• all NHL patients should must: relapsed after or failed to respond to at least two prior systemic treatment regimens, including at least one containing an anti-CD20-directed therapy,, received or be ineligible for autologous SCT , there is no other standard treatment is thought to have clinical benefit
• Dose Expansion:
• Cohort 1: FL patients who are refractory to or relapsed after ≥ 2 prior regimens and have no other standard of care with clinical benefit.
• Cohort 2: r/r DLBCL patients who have progressed after or refractory to 2 or more lines of systemic therapy and have not received prior therapy with CAR-T, and do not have standard treatment with clinical benefit.
• Cohort 3: r/r DLBCL patients who have progressed after or refractory to 2 or more regimens which consisted of a CAR-T therapy that has been approved by a health authority, and do not have standard treatment with clinical benefit.
• \. NHL patients must have expression of CD20 and/or CD19-expression as determined by immunohistochemistry (IHC) at a certified laboratory within 6 months before study entry without intervening treatment of NHL, otherwise a fresh biopsy must be obtained to determine if CD19 and/or CD20 continue to be expressed by tumor cells.
• \. ≥ 1 measurable target lesion as defined by Lugano 2014 criteria (\> 15 mm in its largest dimension for nodal lesions, or \> 10 mm in its largest dimension for extranodal lesion).
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Life expectancy\> 3 months.
• \. Subjects with fertility must take effective contraceptive measures after signing the ICF until at least 12 months after the last administration of 1A46.
• \. Clinical laboratory values as specified below during the screening period.
• ① Total bilirubin must be \< 1.5 x the upper limit of the normal range (ULN). Total bilirubin may be elevated up to 3 x ULN if their elevation can be reasonably ascribed to patients with documented Gilbert's Syndrome.

You may not qualify if:

• \. Patient has brain metastasis or other significant neurological conditions. 2. Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period, or intending to become pregnant during the study.
• \. At the time of enrollment, there are active infections, including bacteria, viruses (including EB virus, cytomegalovirus, etc.), fungi, mycobacteria, parasites, or other infections (excluding nail bed fungal infections), or there are any serious infections that require antibiotic intravenous injection treatment or hospitalization treatment (relating to the completion of the course of antibiotics) within the first 4 weeks prior to enrollment.
• \. Treatment with corticosteroids (\> 10 mg daily prednisone or equivalent) or immunosuppressive medication( including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor drugs) ≤ 7 days before the first dose of 1A46, with the following exceptions: local, ocular, intra-articular, nasal, or inhaled corticosteroids, and those who receive corticosteroid replacement therapy due to adrenal insufficiency.
• \. Treatment with any investigational products (including cell or gene therapy) within 5 half-lives of the agent or 4 weeks prior to the first dose of 1A46, whichever is shorter.
• \. Received Systemic anticancer therapy (including I/O therapies) within 5 half-lives of the agent or 4 weeks prior to the first dose of 1A46, whichever is shorter.
• \. Treatment with radiotherapy within 2 weeks before the study entry. If the patients have received radiotherapy within 4 weeks before enrollment, there must be at least one measurable lesion outside the radiotherapy area, or if the patient only has measurable lesion progression after radiotherapy, they can be enrolled.
• \. Treatment with CAR-T within 30 days before the study entry. 9. Treatment with autologous stem cell transplantation therapy within 100 days before the study entry.
• \. Prior allogeneic hematopoietic stem cell transplantation . 11. Priorsolid organ transplantation. 12. Positive human immunodeficiency virus (HIV) antibodies; positive EB virus nucleic acid ; positive Cytomegalovirus nucleic acid positive; Hepatitis C virus (HCV) antibody is positive, and the result of HCV RNA detection is positive; Hepatitis B surface antigen \[HBsAg\] is positive, and hepatitis B virus DNA test result is positive or greater than the upper limit of normal value.
• \. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse. 14. Have ischemic or hemorrhagic cerebrovascular disease, epilepsy, dementia, or ≥ grade 3 gastrointestinal bleeding within the first 6 months (CTCAE, version 5.0) before screening.
• \. Unstable cardiovascular function:
• Myocardial infarction occurred within 6 months prior to enrollment;
• Have experienced unstable angina pectoris within 3 months prior to enrollment; ③ Uncontrolled and clinically significant arrhythmias (such as persistent ventricular tachycardia, ventricular fibrillation, and torsion of the apex);
• \. Inoculate with live virus vaccine within 28 days before enrollment (attenuated live vaccine is not allowed during the study period or until B cells return to normal range after the last trial drug administration).
• \. Have a history of 3-4 levels of immune related adverse events or a history of immune related adverse events requiring discontinuation of medication, except for level 3 endocrine diseases treated with hormone replacement therapy. Subjects who have experienced levels 3-4 ICANS after previous CAR-T treatment.
• \. Any other serious underlying diseases that researchers believe may interfere with treatment, affect patient compliance, or put patients at high risk of treatment-related complications (such as active gastric ulcers, uncontrolled seizures, cerebrovascular events, gastrointestinal bleeding, severe signs and symptoms of coagulation disorders, heart disease), mental, psychological, familial, or geographic conditions.

Sponsors & Collaborators

• BioRay Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100000, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: August 14, 2023
• Study Start: September 12, 2023
• Primary Completion: August 20, 2024
• Study Completion: November 1, 2024
• Last Updated: February 19, 2025

Record last verified: 2025-02

Locations

CN (1)