Glofitamab is expected to break through the curative effect bottleneck of R/R B-NHL

B-cell non-Hodgkin’s lymphoma (B-NHL) is a highly heterogeneous hematological malignancy, and most patients are highly aggressive.
The most common pathological types include diffuse large B-cells Lymphoma (DLBCL), follicular lymphoma (FL).

Although the survival of B-NHL patients has improved significantly in recent years, for patients who have relapsed or are refractory after first-line treatment, the current overall prognosis is still poor, the survival period is short, and effective treatment methods are lacking.

Glofitamab is a new type of bispecific antibody with a novel 2:1 structure.
It binds bivalently to CD20 of B cells and monovalently binds to CD3 of T cells to induce T cell activation and immune response against tumor cells, thereby achieving anti-tumor effect.

Previous in vitro studies have shown that this new bispecific antibody has higher in vitro activity than other 1:1 bispecific antibodies.

Recently, Professor Martin Hutchings and others reported the results of a phase I clinical study, which mainly evaluated the new CD20/CD3 bispecific antibody Glofitamab in patients with relapsed or refractory (R/R) B-NHL Efficacy and safety.

Research methods The phase I dose escalation and dose extension clinical studies included all CD20-positive R/R B-NHL adult patients.

All patients received 1000 mg of Otuzumab pre-treatment (Gpt) 7 days before the first Glofitamab treatment, the purpose is to deplete the B cells in the peripheral blood and tissues to alleviate the severe cytokine release syndrome (CRS) .

The primary research endpoints are the safety of the patient, the pharmacokinetics of Glofitamab and the maximum tolerated dose; the secondary research endpoints include the patient’s total response rate (ORR), duration of response (DOR), duration of complete response (DOCR) and Progression-free survival (PFS), etc.

Research results The study included patients with R/R B-NHL who had received multiple lines of treatment in the past.
The median number of lines in the previous treatment was 3, and the vast majority of patients (155 cases, accounting for 90.
6%) were ineffective in the previous treatment.

A total of 171 eligible patients were included in the dose-escalation phase.
The median age of the patients was 64 years (range 22-85 years), 73 cases were DLBCL, 29 cases were FL-transformed DLBCL (trFL), and 10 cases were chronic lymphocytes.
Richter transformation of leukemia.

The results of the study showed that among the 171 patients with escalating doses, 168 (98.
2%) patients reported adverse events (AEs); 143 (83.
6%) patients reported ≥1 AEs related to Glofitamab; the most common AE is CRS (86/171 cases, 50.
3%; Grade 3 or 4 CRS: 3.
5%).

According to reports, 100 patients (58.
5%) had serious AEs (SAEs), of which 77 (45.
0%) patients were considered to be related to Glofitamab; most of the SAEs occurred during the first cycle of treatment.

Forty-three patients (25.
1%) had neutropenia ≥ grade 3, of which 34 patients (79.
1%) were considered to be related to Glofitamab.

In addition, 5 patients (2.
9%) withdrew from treatment due to AE; 2 patients (1.
2%) developed grade 3 transient immune effector cell-related neurotoxic syndrome-like symptoms.

The ORR and CR rates of all aggressive R/R B-NHL patients (including DLBCL, trFL, primary mediastinal large B-cell lymphoma [PMBCL], mantle cell lymphoma [MCL] and Richter's transformation) were 48.
0% and 33.
1, respectively %; Among them, the ORR and CR rates of DLBCL patients were 41.
1% and 28.
8%, and the ORR and CR rates of trFL patients were 55.
2% and 34.
5%, respectively.

The ORR of the overall patients in all dose groups was 53.
8% (CR rate 36.
8%); the ORR of patients who received the phase II recommended dose (2.
5/10/30 mg) was 65.
7% (CR rate 57.
1%). Among 63 patients who obtained CR, 84.
1% of patients were able to maintain CR, and the longest observation was 27.
4 months.

In addition, in aggressive R/R B-NHL, the median DOR was 5.
5 months (95% confidence interval [CI], 4.
4-unestimable, range 0.
8-28.
8 months), and the median DOCR was not reached ( Range 0.
0-27.
4 months); the proportion of patients who achieved CR still maintained CR at 12 months was 72.
8%.

The median PFS was 2.
9 months (95% CI, 2.
1-3.
9).

In 1-3A FL patients, the median PFS was 11.
8 months (95% CI, 6.
3-24.
2); the median DOR of 31 remission patients was 10.
8 months (95% CI, 3.
8-unestimable); Medium The DOCR was not reached, 19/21 (90.
5%) patients maintained CR for 22.
9 months.

Research conclusions The research results show that the new bispecific antibody Glofitamab has good safety in R/R B-NHL.
The main AE is CRS but can be controlled.
In addition, Glofitamab has received multiple lines of treatment in the past.
RB-NHL patients still have excellent anti-tumor activity, which can enable some patients to obtain long-lasting CR.

References: Martin Hutchings, Franck Morschhauser, Gloria Iacoboni, et al.
Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial.
J Clin Oncol.
2021 Mar 19; JCO2003175.
Stamp "read the original text", we make progress together