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Advanced MalignanciesPhase 1NCT05987605

Phase I/II Clinical Study of 1A46 Drug Substance

A Phase 1 study testing 1A46 Drug Substance in people with Advanced Malignancies, run by BioRay Pharmaceutical Co., Ltd. at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Malignancies
What is being tested?
1A46 Drug Substance
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteChina
Study dates
12 Sep 2023to 1 Nov 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. 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:
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  • 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.
  • 4. 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.
  • 5. ≥ 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).
  • 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Life expectancy> 3 months.
  • 7. Subjects with fertility must take effective contraceptive measures after signing the ICF until at least 12 months after the last administration of 1A46.
  • 8. 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.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be < 3 x ULN. AST and ALT may be elevated up to 5 x ULN if their elevation can be reasonably ascribed to the presence of metastatic disease in liver.
  • Calculated creatinine clearance > 50 mL/min (the Cockcroft-Gault formula). ④ Hemoglobin (Hb) must be ≥ 80 g/L. No transfusion of red blood cells or use of hematopoietic stimulating factors such as TPO within 14 days before the study.
  • Neutrophil count must be >1.0×10^9/L, No granulocyte or granulocyte macrophage colony-stimulating factor and other hematopoietic stimulating factors were used within 14 days before the study.
  • Platelet count must be >75×10^9/L, No platelet transfusion or use of hematopoietic stimulating factors such as TPO and IL-11 within 14 days prior to testing.
  • ⑦ Prothrombin time-international normalized ratio (PT-INR) must be ≤ 1.5. Patients who are appropriately anticoagulated for a preexisting medical condition [e.g., atrial fibrillation] may be eligible with documented and evaluated by investigators and sponsor approval.
  • 9. Recovery to Grade 0-1 from AEs related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy.

Who cannot join

  • 1. 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.
  • 3. 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.
  • 4. 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.
  • 5. 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.
  • 6. 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.
  • 7. 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.
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  • 8. 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.
  • 10. 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.
  • 13. 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.
  • 15. 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);
  • Mobitz type II degree or III degree atrioventricular block; ⑤ Congestive heart failure with a New York Heart Association rating of ≥ 3; ⑥ Left ventricular ejection fraction<50%. 16. Received major surgery < 4 weeks prior to enrollment; (minor surgeries such as catheter insertion and biopsy required by the protocol are not considered as exclusion criteria).
  • 17. 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).
  • 18. Have a history of grade 3-4 allergic reactions to other monoclonal antibody treatments; Or known to be allergic to any component or excipient of the investigational drug. Patients with Level 3 reactions lasting less than 24 hours may be eligible for inclusion after comprehensive evaluation by the researchers.
  • 19. 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.
  • 20. 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.
  • 21. Have had other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma, or squamous cell skin cancer.
  • 22. Autoimmune, liver, and lung diseases that may worsen under immune activation, such as certain autoimmune diseases, cirrhosis, hepatitis, interstitial pneumonia, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, antiphospholipid antibody syndrome, vasculitis, psoriasis history, etc.
  • 23. Thoracic effusion, pericardial effusion, or ascites that require frequent drainage or medical intervention (recurrence within 2 weeks after intervention requires additional intervention).
  • 24. Previous T-cell engaging treatment regimens (including bispecific antibody, CAR-T therapy, etc.) targeting CD19 and CD20, either successively or simultaneously (those who have only received T-cell engaging therapy targeting one of the targets CD19 or CD20can be included).
  • 25. Use Fredericia's QT correction formula to correct heart rate for QT interval (QTCF)>480msec.
  • 26. During the dose increase phase, the body weight is less than 40kg. 27. Subjects judged by the investigator to be unsuitable for participation in this study.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100000

Other trials in China

About this study

Official title: 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 1A46in Adult Subjects with R/R CD20 Positive And/or CD19 Positive B Cell Non-Hodgkin's Lymphoma (B - NHL)

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)

Read the detailed description

This study is an open-label, multicenter, Phase 1 dose escalation and Phase 2 dose expansion study of 1A46 in adult patients with advanced relapsed/refractory (r/r) CD20 and/or CD19positive B-cell NHL for whom there is not available effective standard treatment . This study is the FIH study of 1A46 in China. This FIH study will include a dose escalation (Phase 1 part) and a dose expansion in 3 cohorts (Phase 2 part). If specific criteria for efficacy are met in one or more of the Phase 2 cohorts, a statistically validated number of additional patients will be enrolled with the goal of accelerated approval The starting dose for phase I is C1D1 1μg，C1D8 1μg，C1D15 and C2D1 afterwards 1 μg, followed by 10 dose cohorts. Duration of dose limiting toxicity (DLT) observation is 28 days.One cycle is defined as 21 days. Patients will be scheduled to receive weekly injection of 1A46 for the first cycles (3 weeks) and then for the remaining 15 cycles, the study patients will receive a single injection of 1A46 per cycle (every 3 weeks [Q3W]).

Being tested
1A46 Drug Substance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 1A46 Drug SubstanceDrug

    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

Study groups in NCT05987605
Study groupRoleWhat they receive
1A46 Drug SubstanceExperimentalOne 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)
Receives: Drug: 1A46 Drug Substance

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity (DLT) (Phase I)

    Number of subjects with a DLT

    Measured: Up to 4 weeks

  2. Maximum tolerated dose (MTD) (Phase I)

    Determine maximum tolerated dose (MTD) of BR110

    Measured: Up to 4 weeks

  3. Recommended phase 2 dose (RP2D) (Phase I)

    Determine recommended phase 2 dose (RP2D) of BR110.

    Measured: Up to 48 weeks

  4. Objective response rate (ORR) (Phase II)

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

    Measured: Up to 48 weeks

Secondary outcomes (7)

  1. Number of subjects with adverse events (Phase Ia)

    Number of subjects who experienced an adverse event

    Measured: Up to 48 weeks

  2. Pharmacokinetic concentration

    Describe blood drug concentrations using appropriate statistics based on dose groups and planned time points

    Measured: Up to 48 weeks

  3. Immunogenicity

    Summarize the number of positive cases and positive rate of ADA by dose group and immunogenicity evaluation time points before and after administration and cumulative positive rate

    Measured: Up to 48 weeks

  4. Disease Control Rate (DCR）

    Calculate the DCR of each group of subjects at each evaluation time point separately

    Measured: Up to 48 weeks

  5. Progression-Free Survival (PFS)

    The Kaplan Meier method will be used to calculate the lower quartile (Q1), middle Digits and upper quartile (Q3) and their 95% confidence intervals

    Measured: Up to 48 weeks

  6. Overall Survival (OS)

    The Kaplan Meier method will be used to calculate the lower quartile (Q1), middle Digits and upper quartile (Q3) and their 95% confidence intervals

    Measured: Up to 48 weeks

  7. The proportion of subjects with CR, PR, SD, PD

    Calculate the proportion

    Measured: Up to 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2023
  2. Study start12 Sep 2023
  3. Primary completion20 Aug 2024
  4. Study completion1 Nov 2024

Why it stopped: sponsor's Research and Development strategy adjustment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05987605
Sponsor's protocol ID
BR110-I/II
Status last verified
Feb 2025
First submitted
10 Jul 2023
Last updated
19 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 1A46 Drug Substance in people with Advanced Malignancies, run by BioRay Pharmaceutical Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: sponsor's Research and Development strategy adjustment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (DLT) (Phase I) (time frame: Up to 4 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05987605.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2025.

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