Regeneron's bispecific REGN1979 shows promise in advanced NHL

Regeneron’s bispecific antibody REGN1979 has produced some enticing results in an early-stage non-Hodgkin lymphoma trial, including in patients who had previously been treated with CAR-T therapy.

While CAR-Ts can be powerful, not everyone responds and there are few options for patients where the cell-based therapy has been unsuccessful.

CAR-Ts are also hugely expensive and difficult to manufacture, leaving an opportunity for drugmakers who are able to produce conventional antibody or small molecule therapies producing similar levels of efficacy.

Regeneron revealed the data at the European Hematology Association conference from REGN1979, an investigational bispecific monoclonal antibody designed to trigger tumour killing by binding to both the B-cell tumour protein CD20, and an immune system T-cell receptor, CD3.

This is very early data but Regeneron has cause to be excited by the results in a small group of patients with follicular lymphoma grades 1 to 3a – 13 out of 14 patients responded, to give a 93% response rate.

There was as complete response in 10 out 14 patients, giving a complete response rate of 71%.

There was 57% overall response rate (4 of 7 patients) in diffuse large B-cell lymphoma (DLBCL) treated with REGN1979 80 mg to 160 mg, all of which were complete responses; these included two complete responses in four patients whose disease had progressed after CAR-T treatment.

This was an early-stage dose escalation trial, and results include data from fully-monitored patients as of the March 15 cut-off as well as preliminary results from evaluable patients.

The primary objective was to assess the safety, tolerability and dose-limiting toxicities of REGN1979. Secondary objectives included an evaluation of the pharmacokinetics, immunogenicity and antitumor activity of REGN1979. In the trial, there were no dose-limiting toxicities.

The most common treatment-emergent adverse events (AEs) were pyrexia (83%), cytokine release syndrome (CRS; 57%), chills (54%), infections and infestations (49%), increased C-reactive protein (38%), fatigue (38%), anaemia (36%) and thrombocytopenia (30%). Six patients experienced Grade 3 or higher CRS (7%).

The incidence and severity of CRS declined through optimized pre-medication, even with REGN1979 dose escalation.

Regeneron invented REGN1979 using technology allowing for generation of full-length bispecific antibodies similar to native antibodies that can be produced by standard manufacturing techniques.

The company has four different bispecific antibodies in clinical trials for both solid tumours and blood cancers and expect to add more by the end of the year.

One of the bispecifics, REGN56798 is in development in prostate cancer, as monotherapy and in combination with Libtayo (cemiplimab).