Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

B-cell Lymphoma

Lymphosarcoma

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)

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

Zhu Jun, Doctor

Yuqin Song, Doctor

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)

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 \[Q3W\]).

Clinical Study of 1A46 Drug Substance

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)

Exploring the impact of the production of anti drug antibodies on efficacy and safety

Relationship between dose level causing 100% B-cell depletion in peripheral blood (and PK parameters associated with this) and clinical parameters, including safety and efficacy.

Preliminary exploration of the relationship between pharmacodynamic indicators and efficacy.

To evaluate MRD in NHL patients who achieve a CR using circulating tumor DNA

Determine maximum tolerated dose (MTD) of BR110

Determine recommended phase 2 dose (RP2D) of BR110.

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

Number of subjects who experienced an adverse event

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

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

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

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

Spots Global Cancer Trial Database for 1a46 drug substance