Trial Title:
Phase I/II Clinical Study of 1A46 Drug Substance
NCT ID:
NCT05987605
Condition:
Advanced Malignancies
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
1A46 Drug Substance
Description:
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
Arm group label:
1A46 Drug Substance
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)
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]).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
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:
1. Aggressive NHL (aNHL) : MCL, each subtype of DLBCL and FL3b, PMBCL, high level of B
cell lymphoma, etc.
2. Indolent NHL (iNHL) : including FL1-3 a grade, MZL, small lymphocytic lymphoma, etc.
3. 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.
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.
Exclusion Criteria:
-
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.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Zip:
100000
Country:
China
Status:
Recruiting
Contact:
Last name:
Jun Zhu, Doctor
Phone:
+86 13910333346
Email:
zhujun3346@163.com
Contact backup:
Last name:
Lin Shen, Doctor
Phone:
+86 010-88196561
Email:
doctorshenlin@sina.cn
Start date:
September 12, 2023
Completion date:
April 30, 2030
Lead sponsor:
Agency:
BioRay Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
BioRay Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05987605
